Cited by 755Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchMemory and Neural Mechanisms

The DOI matches its Crossref record; 368 of the 369 references it cites were found in a registry or an index; none of the 276 sources its claims cite is checked for support yet.

Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models

Open access

Webster, Scott J., Bachstetter, Adam D., Nelson, Peter T., Schmitt, Frederick A., Van Eldik, Linda J.·2014·Frontiers in Genetics

DOI 10.3389/fgene.2014.00088PMC PMC4005958

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Abstract

The goal of this review is to discuss how behavioral tests in mice relate to the pathological and neuropsychological features seen in human Alzheimer's disease (AD), and present a comprehensive analysis of the temporal progression of behavioral impairments in commonly used AD mouse models that contain mutations in amyloid precursor protein (APP). We begin with a brief overview of the neuropathological changes seen in the AD brain and an outline of some of the clinical neuropsychological assessments used to measure cognitive deficits associated with the disease. This is followed by a critical assessment of behavioral tasks that are used in AD mice to model the cognitive changes seen in the human disease. Behavioral tests discussed include spatial memory tests [Morris water maze (MWM), radial arm water maze (RAWM), Barnes maze], associative learning tasks (passive avoidance, fear conditioning), alternation tasks (Y-Maze/T-Maze), recognition memory tasks (Novel Object Recognition), attentional tasks (3 and 5 choice serial reaction time), set-shifting tasks, and reversal learning tasks. We discuss the strengths and weaknesses of each of these behavioral tasks, and how they may correlate with clinical assessments in humans. Finally, the temporal progression of both cognitive and non-cognitive deficits in 10 AD mouse models (PDAPP, TG2576, APP23, TgCRND8, J20, APP/PS1, TG2576 + PS1 (M146L), APP/PS1 KI, 5×FAD, and 3×Tg-AD) are discussed in detail. Mouse models of AD and the behavioral tasks used in conjunction with those models are immensely important in contributing to our knowledge of disease progression and are a useful tool to study AD pathophysiology and the resulting cognitive deficits. However, investigators need to be aware of the potential weaknesses of the available preclinical models in terms of their ability to model cognitive changes observed in human AD. It is our hope that this review will assist investigators in selecting an appropriate mouse model, and accompanying behavioral paradigms to investigate different aspects of AD pathology and disease progression.

AI snapshot

Written from the paper’s full text.

TL;DR

This review maps how behavioral tasks used in amyloid precursor protein (APP) mutant mice correspond to the neuropsychological assessments used clinically in Alzheimer's disease (AD), and tabulates the temporal onset of cognitive and non-cognitive deficits across 10 commonly used AD mouse models. It concludes that no single model recapitulates human AD, but that most models show spatial working memory deficits earlier than deficits in other cognitive domains.

Key findings

Across the reviewed models, the earliest observable cognitive impairment is consistently in spatial working memory (assessed by water maze tasks), generally followed by associative learning/reference memory deficits, with recognition memory deficits appearing later (e.g., PDAPP: working memory at 4 months, NOR at 6 months; Tg2576: spatial working memory at 5 months, NOR at 12 months; APP/PS1 KI: RAWM at 9 months, recognition memory at 15 months).
Onset varies substantially by model: J20 shows recognition memory deficits earliest (1–2 months), while APP/PS1 KI shows the latest onset (7–9 months for earliest deficits).
Non-cognitive abnormalities are also present in most models, including increased locomotor activity (J20 and TgCRND8 earliest at ~1 month; PDAPP and Tg2576 at ~3 months; PS1, 3×Tg-AD, and APP23 at ~6–9 months), anxiety, circadian/sleep disruption, and aggression (e.g., APP23 aggression by 6 months).
The review notes that increased aggression presents in as much as 65% of AD patients, and that depressive symptom prevalence in AD is reported to range from 2% to 85%, though little work has examined depressive-like behavior in AD mouse models.

Methods

Narrative review, not primary experimental work: it summarizes human AD neuropathology (ABC scoring of Amyloid, Braak, CERAD), clinical neuropsychological instruments (MMSE, MoCA, SBT, ADAS-cog, Logical Memory I/II, BVRT), and mouse behavioral tasks (MWM, RAWM, Barnes maze, Y-/T-maze, NOR, fear conditioning, passive/active avoidance, DMTP/DMTS, 3- and 5-CSRTT, set-shifting, reversal learning, WWWhich).
The core synthesis is two tables (Table 3 for five APP models: PDAPP, TG2576, APP23, TgCRND8, J20; Table 4 for five APP+PS1/Tau models: APP/PS1, TG2576+PS1(M146L), APP/PS1 KI, 5×FAD, 3×Tg-AD) coding impairment, no impairment, or no data by age, with an asterisk marking first appearance of diffuse amyloid plaques.
No new data, sample sizes, or statistical analyses are reported; findings are drawn from cited primary studies.

Limitations

Stated by the paper: no animal model recapitulates the entirety of AD; most models represent familial AD (FAD), which accounts for only a small percentage of total AD cases; background strain and likely overexpression of mutant human APP genes on brain development and function must always be considered; language-dependent domains (verbal acuity, verbal recall) cannot be modeled in rodents; the WWWhich episodic-like memory task is not comparable to human episodic memory tests because those rely on language; homology between rodent and human 5-CSRTT is "far from perfect."
Stated by the paper: the tables are not an all-encompassing list of mouse models, only examples of commonly used APP-mutation models.
Evident from the text: the tables contain many cells with no available data, and the review documents inconsistent reports across studies for several models (e.g., Tg2576 spatial memory deficits not replicated in some reports; PDAPP recognition memory findings inconsistent), indicating that model-by-model progression claims rest on heterogeneous and sometimes conflicting literature.

Model-written summary. Check it against the paper before relying on it.

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Registry

Crossref · 10.3389/fgene.2014.00088

Cites

368 of 369 references verified1 citation errors · 0 not checkable

Statistics

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Claims the paper makes

0 of 276 cited sources checked · 0 supported · 0 flagged

None of the sources cited for this claim have been checked yet.
In the paper
“Similar to the reported activity disturbances, circadian rhythm disruptions are also observed in many of the AD mouse models”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Circadian rhythm and sleep disruptions
What the sources say
- Not checked yetcites Huitron-Resendiz et al., 2002
- Not checked yetcites Vloeberghs et al., 2004
- Not checked yetcites Wisor et al., 2005
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Other models such as the TG2576 develop the anxiety-like disturbances later at the age of 9–11 months of age”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Anxiety disturbances
What the sources say
- Not checked yetcites Gil-Bea et al., 2007
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“not all murine AD models exhibit anxiety disturbances”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Anxiety disturbances
What the sources say
- Not checked yetcites Arendash et al., 2001b
- Not checked yetcites Lalonde et al., 2002
- Not checked yetcites Webster et al., 2013
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Many AD mouse models also display increased aggressive behavior”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Aggressive behaviors
What the sources say
- Not checked yetcites Moechars et al., 1996
- Not checked yetcites Van Dorpe et al., 2000
- Not checked yetcites Ambree et al., 2006 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“These aggressive disruptions appear to develop later than the onset of cognitive deficits in this model”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Aggressive behaviors
What the sources say
- Not checked yetcites Kelly et al., 2003
- Not checked yetcites Van Dam et al., 2003
- Not checked yetcites Vloeberghs et al., 2006
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Anxiety disturbances have been reported in many of the AD mouse models”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Anxiety disturbances
What the sources say
- Not checked yetcites Moechars et al., 1996
- Not checked yetcites Lalonde et al., 2003
- Not checked yetcites Gil-Bea et al., 2007
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“The APP23 mouse model of AD also shows increased aggressive behaviors”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Aggressive behaviors
What the sources say
- Not checked yetcites Vloeberghs et al., 2006
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“as the severity of the disease progresses, the worse the sleep disturbances become”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Circadian rhythm and sleep disruptions
What the sources say
- Not checked yetcites Smith, 1985
- Not checked yetcites Graves et al., 2001
- Not checked yetcites Huitron-Resendiz et al., 2002
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Depressive-like behaviors have been reported in at least one mouse model of AD”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Depressive symptoms
What the sources say
- Not checked yetcites Filali et al., 2009
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Some cases classified as “high level” of AD neuropathological changes may show subtle or undetectable cognitive impairment, yet all cases with quantifiably “end stage” neocortical NFT pathology show cognitive impairment (Dickson et al., 1995; Berlau et al., 2007; Nelson et al., 2009a, 2012; Abner et al., 2011; Santacruz et al., 2011; Jicha et al., 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Overview of neuropathological changes in AD
What the sources say
- Not checked yetcites Dickson et al., 1995
- Not checked yetcites Berlau et al., 2007 source
- Not checked yetcites Nelson et al., 2009a
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“the current guidelines recognize that AD neuropathologic changes can be present in the brain in the apparent absence of cognitive impairment.”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Overview of neuropathological changes in AD
What the sources say
- Not checked yetcites Hyman et al., 2012
- Not checked yetcites Montine et al., 2012
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“As the disease progresses into the later stages, there is little evidence to support a continued contribution by amyloid plaques to the late-stage AD cognitive decline (Nelson et al., 2009b, 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Overview of neuropathological changes in AD
What the sources say
- Not checked yetcites Nelson et al., 2009b
- Not checked yetcites Nelson et al., 2012
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“a large number of studies have arrived at a common finding, namely, there is a strong link between neocortical NFTs and cognitive decline (Tomlinson et al., 1970; Duyckaerts et al., 1990, 1997, 1998; Mckee et al., 1991; Arriagada et al., 1992;”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Overview of neuropathological changes in AD
What the sources say
- Not checked yetcites Tomlinson et al., 1970
- Not checked yetcites Duyckaerts et al., 1990
- Not checked yetcites Arriagada et al., 1992 source
Strength:boosted· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Not all AD cases fall within the standard NFT distribution described by the Braak staging (Hof et al., 1997; Abner et al., 2011; Murray et al., 2011).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Overview of neuropathological changes in AD
What the sources say
- Not checked yetcites Hof et al., 1997
- Not checked yetcites Abner et al., 2011 source
- Not checked yetcites Murray et al., 2011
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“First, the strongest correlation between amyloid plaques and cognition is in the early stages of the disease and this association weakens as NFTs and gross neocortical neurodegeneration become more widespread (Thal et al., 2002; Nelson et al., 2009b, 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Overview of neuropathological changes in AD
What the sources say
- Not checked yetcites Thal et al., 2002
- Not checked yetcites Nelson et al., 2009b
- Not checked yetcites Nelson et al., 2012
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“In the earliest stages of AD (Braak stage I-II), NFTs are restricted to the entorhinal cortex (Braak and Del Tredici, 2011; Braak et al., 2011).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Overview of neuropathological changes in AD
What the sources say
- Not checked yetcites Braak and Del Tredici, 2011
- Not checked yetcites Braak et al., 2011
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Consistently, the earliest observable impairments are in spatial working memory (Webster et al., 2013), as assessed through the use of water maze based tasks.”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Webster et al., 2013
Strength:boosted· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Semantic memory deficits are the next to develop (Tuokko et al., 2005; Storandt et al., 2006), followed by impairments in executive functioning (Bondi et al., 2008), attention (Bondi et al., 2008), and visuospatial memory (Twamley et al., 2006) near the beginning of the MCI phase of the disease.”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Bondi et al., 2008
- Not checked yetcites Twamley et al., 2006
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Semantic memory deficits are the next to develop (Tuokko et al., 2005; Storandt et al., 2006), followed by impairments in executive functioning (Bondi et al., 2008), attention (Bondi et al., 2008), and visuospatial memory (Twamley et al., 2006) near the beginning of the MCI phase of the disease.”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Tuokko et al., 2005
- Not checked yetcites Storandt et al., 2006
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“As MCI progresses, deficits in verbal recall (Kryscio et al., 2006; Bondi et al., 2008) develop and impairments in general cognition (Bondi et al., 2008) become apparent.”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Kryscio et al., 2006
- Not checked yetcites Bondi et al., 2008
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“For example, if the patient has a high number of perseveration errors it is likely that the AD pathology has manifest itself in neocortical areas responsible for higher cognitive domains such as executive function, and visuospatial capacities (Braak Stage V–VI).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Memory tests
What the sources say
- Not checked yetcites Braak Stage V–VI
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“In the human disease, the earliest AD-related cognitive deficits present themselves as episodic memory impairment during the late preclinical phase of the disease (Backman et al., 2005; Twamley et al., 2006; Bondi et al., 2008).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Backman et al., 2005 source
- Not checked yetcites Twamley et al., 2006
- Not checked yetcites Bondi et al., 2008
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Some cases classified as “high level” of AD neuropathological changes may show subtle or undetectable cognitive impairment, yet all cases with quantifiably “end stage” neocortical NFT pathology show cognitive impairment (Dickson et al., 1995; Berlau et al., 2007; Nelson et al., 2009a, 2012; Abner et al., 2011; Santacruz et al., 2011; Jicha et al., 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Overview of neuropathological changes in AD
What the sources say
- Not checked yetcites Dickson et al., 1995
- Not checked yetcites Berlau et al., 2007 source
- Not checked yetcites Nelson et al., 2009a
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“As MCI progresses, deficits in verbal recall (Kryscio et al., 2006; Bondi et al., 2008) develop and impairments in general cognition (Bondi et al., 2008) become apparent.”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Bondi et al., 2008
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This suggests that cognitive functions such as episodic and semantic memory that depend heavily on the neural circuitry of the medial and lateral temporal lobes may be impaired earlier than cognitive abilities that depend on the circuitry of other brain regions.”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- Rests on an assumption: Some of the earliest neuropathological changes in AD are in the hippocampus and entorhinal cortex, followed by changes in the medial temporal lobe.
None of the sources cited for this claim have been checked yet.
In the paper
“Most studies of MCI patients show consistent impairments in verbal recall (Larrieu et al., 2002; Tuokko et al., 2005; Kryscio et al., 2006) and a decline in general memory functioning (Tuokko et al., 2005; Bondi et al., 2008).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Larrieu et al., 2002
- Not checked yetcites Tuokko et al., 2005
- Not checked yetcites Kryscio et al., 2006
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Most studies of MCI patients show consistent impairments in verbal recall (Larrieu et al., 2002; Tuokko et al., 2005; Kryscio et al., 2006) and a decline in general memory functioning (Tuokko et al., 2005; Bondi et al., 2008).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Tuokko et al., 2005
- Not checked yetcites Bondi et al., 2008
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“These impairments are generally followed temporally by impairments in associative learning and reference memory, as assessed by maze alternation (Lalonde et al., 2012) and fear conditioning tasks (Kobayashi and Chen, 2005).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Lalonde et al., 2012
- Not checked yetcites Kobayashi and Chen, 2005
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Consistent with this progression of pathology, the earliest detectable deficits in cognition are seen in medial temporal lobe-dependent episodic memory (Bondi et al., 1999; Collie and Maruff, 2000; Schmitt et al., 2000; Smith et al., 2007).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Bondi et al., 1999
- Not checked yetcites Collie and Maruff, 2000
- Not checked yetcites Schmitt et al., 2000
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- Rests on an assumption: Some of the earliest neuropathological changes in AD are in the hippocampus and entorhinal cortex, followed by changes in the medial temporal lobe.
None of the sources cited for this claim have been checked yet.
In the paper
“Slight deficits in executive functioning are first detectable near the end of the preclinical phase of AD but after the observed deficits in episodic and semantic memory (Storandt et al., 2006; Twamley et al., 2006).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Storandt et al., 2006
- Not checked yetcites Twamley et al., 2006
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Deficits in recognition memory usually present later in the spectrum of cognitive impairment than deficits in other domains (Eriksen and Janus, 2007; Hall and Roberson, 2012; Webster et al., 2013).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Eriksen and Janus, 2007
- Not checked yetcites Hall and Roberson, 2012
- Not checked yetcites Webster et al., 2013
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“However, animals with prefrontal cortex lesions display profound deficits in reversal learning (Chudasama, 2011; Izquierdo and Jentsch, 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling executive function
What the sources say
- Not checked yetcites Chudasama, 2011
- Not checked yetcites Izquierdo and Jentsch, 2012
Strength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“In both the Wisconsin Card Sorting Task in humans and set-shifting tasks in mice, the dorsolateral and orbital prefrontal cortex is critical for successful performance (Weinberger et al., 1986; Berman et al., 1995; Brigman et al., 2005; Bissonette et al., 2008).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling executive function
What the sources say
- Not checked yetcites Weinberger et al., 1986
- Not checked yetcites Berman et al., 1995 source
- Not checked yetcites Brigman et al., 2005
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“While less complex than attentional set shifting, reversal learning does require both cognitive flexibility and impulse control, thus tapping into components of human executive function (Chudasama, 2011; Stopford et al., 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling executive function
What the sources say
- Not checked yetcites Chudasama, 2011
- Not checked yetcites Stopford et al., 2012
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Other examples of non-spatial working memory tasks are operant tasks such as the Delayed Match to Sample (DMTS), Delayed Non-Match to Sample (DNMTS), and Delayed Stimulus Discrimination Task (DSDT) (Dudchenko, 2004; Buccafusco et al., 2008).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling working memory
What the sources say
- Not checked yetcites Dudchenko, 2004
- Not checked yetcites Buccafusco et al., 2008
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“For example, there exist versions of both the RAM and RAWM that are considered non-spatial working memory tasks (Olton and Feustle, 1981; Crusio et al., 1993; Hyde et al., 2000).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling working memory
What the sources say
- Not checked yetcites Olton and Feustle, 1981
- Not checked yetcites Crusio et al., 1993
- Not checked yetcites Hyde et al., 2000
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“This lends itself nicely to pharmacological based studies assessing potential therapeutic compounds for the treatment of the cognitive deficits seen in AD (Buccafusco et al., 2008).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling working memory
What the sources say
- Not checked yetcites Buccafusco et al., 2008
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Numerous different transgenic mouse models of AD have shown deficits in set-shifting tasks (Zhuo et al., 2007, 2008; Marchese et al., 2013).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling executive function
What the sources say
- Not checked yetcites Zhuo et al., 2007, 2008
- Not checked yetcites Marchese et al., 2013
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Similarly, many different AD mouse models have shown impairment in reversal learning (Angelo et al., 2003; Dong et al., 2005; Filali et al., 2012; Cheng et al., 2013; Musilli et al., 2013; Papadopoulos et al., 2013).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling executive function
What the sources say
- Not checked yetcites Angelo et al., 2003 source
- Not checked yetcites Dong et al., 2005
- Not checked yetcites Filali et al., 2012
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“In the WWWhich task, the animal must integrate the location of a particular object with specific contextual cues to form an episodic-like memory (Davis et al., 2013a,b).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling episodic memory
What the sources say
- Not checked yetcites Davis et al., 2013a,b
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“The 5-CSRTT can test two different aspects of response inhibition: (1) a failure to withhold the impulsive urge to respond while anticipating correct response (premature responses) and (2) a failure to disengage from repeating past correct responses (perseveration responses) (Chudasama, 2011).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling executive function
What the sources say
- Not checked yetcites Chudasama, 2011
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Several studies employing the WWWhich task have observed performance deficits related to the aging process and to AD disease state in several transgenic mouse lines (Davis et al., 2013a,b).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling episodic memory
What the sources say
- Not checked yetcites Davis et al., 2013a,b
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Another task that can be considered somewhat analogous to the 5-CSRTT is the human Continuous Performance Tests (CPT) of sustained attention (Beck et al., 1956).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling attention
What the sources say
- Not checked yetcites Beck et al., 1956 source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Several mouse models of AD have shown deficits in response inhibition using the 5-CSRTT (Romberg et al., 2011, 2013b).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling executive function
What the sources say
- Not checked yetcites Romberg et al., 2011, 2013b
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Aspects of selective attention can also be modeled with the 5-CSRTT by introducing brief bursts of white noise that the animal must ignore while still detecting the visual stimulus as it is presented (Robbins, 2002; Bari et al., 2008).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling attention
What the sources say
- Not checked yetcites Robbins, 2002
- Not checked yetcites Bari et al., 2008 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“The rodent 5-CSRTT is analogous to Leonard's 5-CSRTT used in humans (Wilkinson, 1963).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling attention
What the sources say
- Not checked yetcites Wilkinson, 1963
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“AD mice such as the 3×Tg-AD mice have been shown to have deficits in sustained attention using the 5-CSRTT (Romberg et al., 2011).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling attention
What the sources say
- Not checked yetcites Romberg et al., 2011
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“The most widely used of these tasks is the 5-CSRTT (Muir, 1996; Humby et al., 1999; Robbins, 2002; De Bruin et al., 2006; Gibson et al., 2006; Lambourne et al., 2007; Pattij et al., 2007).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling attention
What the sources say
- Not checked yetcites Muir, 1996
- Not checked yetcites Humby et al., 1999
- Not checked yetcites Robbins, 2002
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“The five choice serial reaction time task (5-CSRTT) is a behavioral task that measures the response inhibition component of executive function (5-CSRTT is also used to model aspects of attention, see below section) in mice (Robbins, 2002; Bari et al., 2008; Chudasama, 2011; Romberg et al., 2013a).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling executive function
What the sources say
- Not checked yetcites Robbins, 2002
- Not checked yetcites Bari et al., 2008 source
- Not checked yetcites Chudasama, 2011
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“In the Tg2576 mouse (Hsiao et al., 1996), the first presentation of cognitive deficits is seen at 5 months of age in spatial working memory (Arendash et al., 2004).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > TG2576
What the sources say
- Not checked yetcites Arendash et al., 2004 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“In this model, the cognitive deficits begin to first appear in both recognition memory and spatial working memory at 3 months of age.”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP23
What the sources say
- Not checked yetcites Sturchler-Pierrat et al., 1997
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“However, methodology used to assess spatial memory appears to be very important, as several different reports have failed to observe these same deficits at various ages (Hsiao et al., 1996; Arendash et al., 2001a; King and Arendash, 2002).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > TG2576
What the sources say
- Not checked yetcites Hsiao et al., 1996
- Not checked yetcites Arendash et al., 2001a
- Not checked yetcites King and Arendash, 2002
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“This model develops non-spatial working memory deficits very late in the progression of the disease (only after 19 months of age) (Lalonde et al., 2002; Dumont et al., 2004).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP23
What the sources say
- Not checked yetcites Lalonde et al., 2002
- Not checked yetcites Dumont et al., 2004
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Non-spatial working memory tasks show a similar time course progression, first appearing at 3–5 months of age and persisting across the lifespan (Hsiao et al., 1996; Chapman et al., 1999; King and Arendash, 2002; Lalonde et al., 2003; Ohno et al., 2004).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > TG2576
What the sources say
- Not checked yetcites Hsiao et al., 1996
- Not checked yetcites Chapman et al., 1999
- Not checked yetcites King and Arendash, 2002
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Deficits in recognition memory do not appear until much later, first appearing at 12 months of age in the NOR task (Oules et al., 2012; Yassine et al., 2013).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > TG2576
What the sources say
- Not checked yetcites Oules et al., 2012
- Not checked yetcites Yassine et al., 2013
Strength:hedged· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“The TgCRND8 model, described by Chishti et al. (2001), exhibits early cognitive impairment that spans across multiple cognitive domains (Chishti et al., 2001).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > TgCRND8
What the sources say
- Not checked yetcites Chishti et al., 2001
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“These spatial working memory deficits are generally accepted to be present across the rest of the life span for this model (Hsiao et al., 1996; Westerman et al., 2002; Arendash et al., 2004).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > TG2576
What the sources say
- Not checked yetcites Hsiao et al., 1996
- Not checked yetcites Westerman et al., 2002
- Not checked yetcites Arendash et al., 2004 source
Strength:boosted· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“In this model, the cognitive deficits first present themselves in spatial working memory at 4 months of age when assessed by MWM testing (Hartman et al., 2005).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > PDAPP
What the sources say
- Not checked yetcites Hartman et al., 2005
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Interestingly, cognitive performance in passive avoidance memory tasks follows the same progression as non-spatial working memory deficits in this model, unimpaired at 15 months of age and then developing deficits between 19 and 20 months of age (Kelly et al., 2003).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP23
What the sources say
- Not checked yetcites Kelly et al., 2003
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“These deficits in working memory in the MWM are present throughout the rest of the life span for this model (Chen et al., 2000; Daumas et al., 2008).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > PDAPP
What the sources say
- Not checked yetcites Chen et al., 2000
- Not checked yetcites Daumas et al., 2008
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“The cognitive defects in this model appear to present themselves before the appearance of plaque deposition (first appear at approximately 6 months) or other gross amyloid pathologies (Games et al., 1995; Hsiao et al., 1996; Schenk et al., 1999; Chen et al., 2000; Morgan, 2003).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > PDAPP
What the sources say
- Not checked yetcites Games et al., 1995
- Not checked yetcites Hsiao et al., 1996
- Not checked yetcites Schenk et al., 1999
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Reference memory deficits via Barnes maze testing are also present at 3 months of age (Gortz et al., 2008; Richter et al., 2008; Ambree et al., 2009).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > TgCRND8
What the sources say
- Not checked yetcites Gortz et al., 2008
- Not checked yetcites Richter et al., 2008
- Not checked yetcites Ambree et al., 2009 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Deficits in alternation tasks develop by 6 and 9 months in Y-maze and T-maze alternation tasks, respectively (Hyde et al., 2005).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > TgCRND8
What the sources say
- Not checked yetcites Hyde et al., 2005
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Similar to this observed temporal time course of spatial working memory and reference memory deficits are the development of deficits in both recognition memory and fear conditioning (Gortz et al., 2008; Richter et al., 2008; Ambree et al., 2009; Hanna et al., 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > TgCRND8
What the sources say
- Not checked yetcites Gortz et al., 2008
- Not checked yetcites Richter et al., 2008
- Not checked yetcites Ambree et al., 2009 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Early memory deficits can also be observed in spatial working memory at 3 months of age when assessed by the MWM and the RAWM tasks (Lustbader et al., 2004; Cheng et al., 2007; Meilandt et al., 2008).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > J20
What the sources say
- Not checked yetcites Lustbader et al., 2004
- Not checked yetcites Cheng et al., 2007
- Not checked yetcites Meilandt et al., 2008
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“This model is unique in that the first presented cognitive deficits are observed very early (at 1–2 months of age) in recognition memory (Harris et al., 2010).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > J20
What the sources say
- Not checked yetcites Harris et al., 2010
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Deficits in associative learning have also been described in fear conditioning tasks starting at 6–8 months of age (Knafo et al., 2009; Cramer et al., 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP/PS1
What the sources say
- Not checked yetcites Knafo et al., 2009
- Not checked yetcites Cramer et al., 2012
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Interestingly, this model does not appear to display working memory deficits on tasks of alternation such as the Y-maze (Murakami et al., 2011; Karl et al., 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > J20
What the sources say
- Not checked yetcites Murakami et al., 2011
- Not checked yetcites Karl et al., 2012
Strength:hedged· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“These deficits in recognition memory are present when assessed at several other time points (Escribano et al., 2009; Simon et al., 2009; Cisse et al., 2011).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > J20
What the sources say
- Not checked yetcites Escribano et al., 2009
- Not checked yetcites Simon et al., 2009
- Not checked yetcites Cisse et al., 2011
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Fear conditioning deficits appear consistent with the presentation of spatial working memory and recognition memory deficits in this model (Saura et al., 2005).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > J20
What the sources say
- Not checked yetcites Saura et al., 2005
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“These spatial working memory deficits are present across the rest of this model's lifespan (Palop et al., 2003; Galvan et al., 2006; Cisse et al., 2011; Du et al., 2011; Murakami et al., 2011; Fang et al., 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > J20
What the sources say
- Not checked yetcites Palop et al., 2003
- Not checked yetcites Galvan et al., 2006
- Not checked yetcites Cisse et al., 2011
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Further, these deficits have been well characterized across the lifespan of this mouse model in water based spatial working memory tasks (Lalonde et al., 2005; Park et al., 2006; Cao et al., 2007; Sood et al., 2007; Ding et al., 2008; Volianskis et al., 2010; Zhang et al., 2011; Cramer et al., 2012; Ma et al., 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP/PS1
What the sources say
- Not checked yetcites Lalonde et al., 2005
- Not checked yetcites Park et al., 2006
- Not checked yetcites Cao et al., 2007
Strength:boosted· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Similarly, deficits in recognition memory occur later in this model, first observed at 12 months of age (Mori et al., 2013).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP + PS1
What the sources say
- Not checked yetcites Mori et al., 2013
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“As with several of the other models (PDAPP, Tg2576, APP/PS1, and APP/PS1 KI) this model develops deficits in recognition memory later than the observed deficits in spatial working memory (Tohda et al., 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > 5×FAD
What the sources say
- Not checked yetcites Tohda et al., 2012
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“No deficits were seen in alternation tasks of working memory for this model (Lalonde et al., 2004; Cao et al., 2007).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP/PS1
What the sources say
- Not checked yetcites Lalonde et al., 2004
- Not checked yetcites Cao et al., 2007
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“No deficits were observed in alternation tasks of working memory (Holcomb et al., 1998; Arendash et al., 2001a).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP + PS1
What the sources say
- Not checked yetcites Holcomb et al., 1998
- Not checked yetcites Arendash et al., 2001a
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“We have shown previously that the cognitive deficits in spatial working memory (assessed by RAWM testing) first appear at 9 months of age (Webster et al., 2013).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP/PS1 KI
What the sources say
- Not checked yetcites Webster et al., 2013
Strength:boosted· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“The earliest reports of cognitive deficits are reported at 7 months in this model (Bruce-Keller et al., 2011).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP/PS1 KI
What the sources say
- Not checked yetcites Bruce-Keller et al., 2011
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Similarly, passive avoidance deficits have also been described at 12 months of age (Zhang et al., 2011).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP/PS1
What the sources say
- Not checked yetcites Zhang et al., 2011
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“By 15 months of age the spatial working memory is consistently impaired throughout the rest of the life span (Morgan et al., 2000; Arendash et al., 2001b; Gordon et al., 2001; Sadowski et al., 2004; Wilcock et al., 2004).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP + PS1
What the sources say
- Not checked yetcites Morgan et al., 2000
- Not checked yetcites Arendash et al., 2001b
- Not checked yetcites Gordon et al., 2001
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“The 5×FAD model, first described by Oakley et al. (2006), develops progressive cognitive deficits with age.”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > 5×FAD
What the sources say
- Not checked yetcites Oakley et al., 2006
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“This model develops cognitive deficits by 3 months of age in spatial working memory (Ohno et al., 2006; Urano and Tohda, 2010).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > 5×FAD
What the sources say
- Not checked yetcites Ohno et al., 2006
- Not checked yetcites Urano and Tohda, 2010
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“However, these cognitive deficits are not robust at this age, as others have observed no such deficit (Holcomb et al., 1999; Arendash et al., 2001a).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP + PS1
What the sources say
- Not checked yetcites Holcomb et al., 1999
- Not checked yetcites Arendash et al., 2001a
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“The first reported impairment in spatial working memory was observed using 6-month-old animals (Trinchese et al., 2004).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP + PS1
What the sources say
- Not checked yetcites Trinchese et al., 2004
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Most of the commonly used AD mouse models exhibit increased locomotor activity (Dodart et al., 1999; King et al., 1999; Arendash et al., 2001b; Dumont et al., 2004; Hyde et al., 2005; Cheng et al., 2007; Gil-Bea et al., 2007; Pietropaolo et al., 2008; Sanchez-Mejia et al., 2008; Ambree et al., 2009; Cisse et al., 2011; Mori et al., 2013).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Locomotor activity
What the sources say
- Not checked yetcites Dodart et al., 1999
- Not checked yetcites King et al., 1999
- Not checked yetcites Arendash et al., 2001b
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“The 3×Tg-AD mouse model, developed by Oddo et al. (2003), shows progressive cognitive impairments starting at a young age.”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > 3×Tg-AD
What the sources say
- Not checked yetcites Oddo et al., 2003
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“and have been linked to altered APP metabolism, amyloid levels, and disease progression (Van Someren et al., 1996; Harper et al., 2004).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Locomotor activity
What the sources say
- Not checked yetcites Van Someren et al., 1996
- Not checked yetcites Harper et al., 2004
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“Likewise, in the APP23 mice there have been reports of increased activity in the second half of the nocturnal phase (end of the active phase of the wake cycle) (Vloeberghs et al., 2004).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Locomotor activity
What the sources say
- Not checked yetcites Vloeberghs et al., 2004
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Non-cognitive neuropsychological symptoms associated with AD include activity disturbances, affective disturbances, aggression, stereotypic behavior, circadian rhythm disturbances, and anxiety (Ancoli-Israel et al., 1989; Okawa et al., 1991; Vitiello et al., 1992; Bliwise, 1994; Satlin et al., 1995; Van Someren et al., 1996; Hope et al., 1998; Harper et al., 2004; Shin et al., 2005; Tan et al., 2”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models
What the sources say
- Not checked yetcites Ancoli-Israel et al., 1989 source
- Not checked yetcites Okawa et al., 1991
- Not checked yetcites Vitiello et al., 1992
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“Circadian rhythm disturbances have also been well described in human AD patients”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Circadian rhythm and sleep disruptions
What the sources say
- Not checked yetcites Ancoli-Israel et al., 1989 source
- Not checked yetcites Okawa et al., 1991
- Not checked yetcites Vitiello et al., 1992
Strength:boosted· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
In the paper
“For example, in the TgCRND8 mice, the deficits seem most severe near the end of their wake cycle and less severe at other times of the day (Ambree et al., 2006).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Locomotor activity
What the sources say
- Not checked yetcites Ambree et al., 2006 source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
None of the sources cited for this claim have been checked yet.
In the paper
“patients with a history of depression prior to a diagnosis of AD are much more likely to experience depressive episodes in the course of AD”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Depressive symptoms
What the sources say
- Not checked yetcites Pearlson et al., 1990
- Not checked yetcites Strauss and Ogrocki, 1996
Strength:boosted· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes

It may state two separate claims as one. 41
The quote only partly states this claim. 1
Probably not a substantial claim. 24

None of the sources cited for this claim have been checked yet.
In the paper
“The onset of the disturbances is different for each model, with the J20 and the TgCRND8 mice developing disruptions earliest (approximately 1 month of age), followed by PDAPP and TG2576 (approximately 3 months of age), and the PS1 [Tg2576 + PS1 (M146L)], 3×TgAD, and APP23 mice developing last (approximately 6–9 months of age)”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Locomotor activity
What the sources say
- Not checked yetcites Dodart et al., 1999
- Not checked yetcites King et al., 1999
- Not checked yetcites Arendash et al., 2001b
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Other AD mouse models that show activity disturbances are the PDAPP, TG2576, J20, APP + PS1 [Tg2576 + PS1 (M146L)], and 3×Tg-AD mouse models of AD.”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Locomotor activity
What the sources say
- Not checked yetcites Dodart et al., 1999
- Not checked yetcites King et al., 1999
- Not checked yetcites Arendash et al., 2001b
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the greater the sleep disruptions are, the more severe the cognitive decline seems to be”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Circadian rhythm and sleep disruptions
What the sources say
- Not checked yetcites Huitron-Resendiz et al., 2002
- Not checked yetcites Huitron-Resendiz et al., 2005
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
The quote only partly states this claim.
In the paper
“in the TG2576 mouse increased aggressive behaviors display themselves in both the frequency of attacks on other home cage mice as well as on the latency to first attack when interacting with a novel mouse”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Aggressive behaviors
What the sources say
- Not checked yetcites Alexander et al., 2011 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“in some models the behavioral disturbances start early at 1–2 months of age or 3–6 months of age for the J20 and the APP/PS1 models, respectively”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Anxiety disturbances
What the sources say
- Not checked yetcites Lalonde et al., 2004
- Not checked yetcites Reiserer et al., 2007
- Not checked yetcites Harris et al., 2010
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“NFTs spread to the limbic and medial temporal lobe (Braak stage III-IV), and this stage correlates with early AD symptoms related to memory (Schmitt et al., 2000; Riley et al., 2011).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Overview of neuropathological changes in AD
What the sources say
- Not checked yetcites Schmitt et al., 2000
- Not checked yetcites Riley et al., 2011
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“Because the ADAS-cog has an excellent test-retest reliability and is considered to be one of the most sensitive scales for assessing cognitive changes related to AD (Emilien et al., 2004), this test is extensively used in AD clinical trials as an outcome measure of cognitive change (Schmitt and Wichems, 2006; Connor and Sabbagh, 2008).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Mental status exams
What the sources say
- Not checked yetcites Emilien et al., 2004
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Because the ADAS-cog has an excellent test-retest reliability and is considered to be one of the most sensitive scales for assessing cognitive changes related to AD (Emilien et al., 2004), this test is extensively used in AD clinical trials as an outcome measure of cognitive change (Schmitt and Wichems, 2006; Connor and Sabbagh, 2008).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Mental status exams
What the sources say
- Not checked yetcites Schmitt and Wichems, 2006
- Not checked yetcites Connor and Sabbagh, 2008
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The MMSE has excellent reproducibility that lends itself well to longitudinal use in tracking the progression of the cognitive impairments associated with AD (Jacqmin-Gadda et al., 1997; Aevarsson and Skoog, 2000; Chatfield et al., 2007).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Mental status exams
What the sources say
- Not checked yetcites Jacqmin-Gadda et al., 1997
- Not checked yetcites Aevarsson and Skoog, 2000 source
- Not checked yetcites Chatfield et al., 2007
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Another commonly used test battery is that of the Short Blessed Test (SBT) which consists of a six-item test designed to identify the cognitive dysfunction seen in AD (Katzman et al., 1983).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Mental status exams
What the sources say
- Not checked yetcites Katzman et al., 1983
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Despite the simplicity and brevity of the SBT, the results that it produces have demonstrated excellent reliability (Fuld, 1978).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Mental status exams
What the sources say
- Not checked yetcites Fuld, 1978
Strength:boosted· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Similarly, the SBT was the first mental status examination to be correlated with amyloid plaque burden at autopsy (Carpenter et al., 2011).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Mental status exams
What the sources say
- Not checked yetcites Carpenter et al., 2011
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The Mini-Mental Status Examination (MMSE) is one of the most commonly used neuropsychological screening tools for cognitive impairments seen in AD (Simard and Van Reekum, 1999; Snyderman and Rovner, 2009).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Mental status exams
What the sources say
- Not checked yetcites Simard and Van Reekum, 1999
- Not checked yetcites Snyderman and Rovner, 2009
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The data also support the “Amyloid Cascade Hypothesis”(Karran et al., 2011), a deceptively complex hypothesis which posits that beta-amyloid/plaque pathology kindles widespread tau/NFT pathology, with the tau/NFT pathology constituting the more direct cause of the cell loss and synapse elimination underlying clinical disease (Nelson et al., 2009b, 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Overview of neuropathological changes in AD
What the sources say
- Not checked yetcites Karran et al., 2011
- Not checked yetcites Nelson et al., 2009b
- Not checked yetcites Nelson et al., 2012
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: Outside of frontotemporal lobar degeneration (FTLD), one does not see widespread cortical NFTs without abundant plaque pathology.
In the paper
“The Alzheimer's Disease Assessment Scale (ADAS) was specifically developed to measure the severity of symptoms commonly seen in AD (Rosen et al., 1984).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Mental status exams
What the sources say
- Not checked yetcites Rosen et al., 1984
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“These tasks rely on the natural exploratory behavior (tendency to choose an alternative arm over an arm which has been previously explored) of rodents and are considered the most rudimentary tasks to assess spatial working memory (Dudchenko, 2004).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling working memory
What the sources say
- Not checked yetcites Dudchenko, 2004
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Once the AD patient progresses past MCI and into dementia, general cognition continues to decline with deficits appearing in all respective cognitive domains (Huff et al., 1987; Locascio et al., 1995; Lambon Ralph et al., 2003; Mckhann et al., 2011).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Huff et al., 1987
- Not checked yetcites Locascio et al., 1995
- Not checked yetcites Lambon Ralph et al., 2003
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“Large numbers of AD mouse models have been tested in the MWM and most show AD related cognitive deficits (Webster et al., 2013).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling working memory
What the sources say
- Not checked yetcites Webster et al., 2013
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Instead, spatial based working memory tasks are heavily employed in murine working memory testing and likely are more depictive of the visuospatial working memory tasks used clinically (Benton, 1992; Benedict and Groninger, 1994).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling working memory
What the sources say
- Not checked yetcites Benton, 1992
- Not checked yetcites Benedict and Groninger, 1994
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: Working memory is perhaps one of the most well modeled aspects of the memory deficits in AD.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Some cognitive domains disrupted in AD have been extensively modeled (reference memory, working memory and executive function), some less so (attention), and some nearly not at all (episodic memory).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD?
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: Other cognitive domains impaired in human AD such as those involving language (i.e., verbal acuity tasks and verbal recall tasks) simply cannot be modeled in rodent models.
None of the sources cited for this claim have been checked yet.
In the paper
“Clinically, many of the neuropsychological tests that assess working memory rely heavily on the use of verbal tasks (Kaplan et al., 1978; Benedict et al., 1998; Spreen and Strauss, 1998; Delis et al., 2000), employing language as a core construct and thus are not feasible to model using mice.”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling working memory
What the sources say
- Not checked yetcites Kaplan et al., 1978
- Not checked yetcites Benedict et al., 1998 source
- Not checked yetcites Spreen and Strauss, 1998
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
- Rests on an assumption: Other cognitive domains impaired in human AD such as those involving language (i.e., verbal acuity tasks and verbal recall tasks) simply cannot be modeled in rodent models.
In the paper
“Composite scores encompassing multiple neuropsychological tests are often used and can provide some of the most reliable assessments of global cognitive status relating to AD as well as serving as efficacy outcome measures in clinical trials (Bernick et al., 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Bernick et al., 2012 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“These early deficits in episodic memory are followed closely by deficits in semantic memory, and both are developed before other deficits in cognitive domains such as attention, visuospatial memory, or executive function (Bondi et al., 2008).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Cognitive neuropsychological assessments used in the AD field > Cognitive neuropsychological assessment summary
What the sources say
- Not checked yetcites Bondi et al., 2008
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“Perhaps the most widely employed spatial working memory task is that of the Morris Water Maze (MWM) (Morris et al., 1982).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling working memory
What the sources say
- Not checked yetcites Morris et al., 1982
Strength:hedged· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Other common tasks of murine spatial working memory are the Radial Arm Water Maze (RAWM) and the Barnes Maze (Barnes, 1979; Diamond et al., 1999; Alamed et al., 2006).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling working memory
What the sources say
- Not checked yetcites Barnes, 1979 source
- Not checked yetcites Diamond et al., 1999
- Not checked yetcites Alamed et al., 2006 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Depending on the baiting paradigm, unimpaired rats and mice will quickly learn where the food reward is and which arms have previously been visited, and will avoid re-entering a previously entered arm.”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling working memory
What the sources say
- Not checked yetcites Olton and Samuelson, 1976
- Not checked yetcites Olton et al., 1979
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Response inhibition is required for the appropriate control of an individual's behavioral actions in response to a stimulus (Robbins, 1996; Humby et al., 1999; Perry and Hodges, 1999; Romberg et al., 2013a).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling executive function
What the sources say
- Not checked yetcites Robbins, 1996
- Not checked yetcites Humby et al., 1999
- Not checked yetcites Perry and Hodges, 1999
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“In many ways, set-shifting tasks are similar to the Wisconsin Card Sorting Task in that they form the gold standard for assessing executive function (Drewe, 1974; Robinson et al., 1980; Arnett et al., 1994).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling executive function
What the sources say
- Not checked yetcites Drewe, 1974
- Not checked yetcites Robinson et al., 1980
- Not checked yetcites Arnett et al., 1994 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Cognitive decline is a defining feature of AD, and many mouse models have been developed that recapitulate aspects of the cognitive impairments seen in AD (Elder et al., 2010; Hochgrafe et al., 2013; Platt et al., 2013).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models
What the sources say
- Not checked yetcites Elder et al., 2010
- Not checked yetcites Hochgrafe et al., 2013
- Not checked yetcites Platt et al., 2013
Load-bearingStrength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, work over the past few decades on episodic-like memory across a number of animal species has suggested otherwise, and several mouse behavioral tasks designed at assessing episodic-like memory have been developed (Clayton and Dickinson, 1998; Clayton et al., 2001; Griffiths and Clayton, 2001; Morris, 2001; Davis et al., 2013a,b).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling episodic memory
What the sources say
- Not checked yetcites Clayton and Dickinson, 1998
- Not checked yetcites Clayton et al., 2001
- Not checked yetcites Griffiths and Clayton, 2001
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“Historically, episodic memory was thought to be unique to humans (Tulving and Markowitsch, 1998).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling episodic memory
What the sources say
- Not checked yetcites Tulving and Markowitsch, 1998
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Touchscreen versions of this task are also available in which the nose poke holes and stimulus lights are replaced with an LCD screen (Romberg et al., 2011; Bussey et al., 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > How commonly used preclinical mouse behavioral tasks relate to the clinical neuropsychological assessment tests in human AD? > Modeling attention
What the sources say
- Not checked yetcites Romberg et al., 2011
- Not checked yetcites Bussey et al., 2012
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Deficits in recognition memory appear to develop after the working memory deficits in this model, as the first reported deficits in the NOR task are at 6 months old (Dodart et al., 1999).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > PDAPP
What the sources say
- Not checked yetcites Dodart et al., 1999
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“TgCRND8 are impaired on spatial working memory tasks starting at 3 months of age. These deficits are seen in the MWM and progress with age of the animal (Janus et al., 2000; Chishti et al., 2001; Gortz et al., 2008; Richter et al., 2008; Ambree et al., 2009).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > TgCRND8
What the sources say
- Not checked yetcites Janus et al., 2000
- Not checked yetcites Chishti et al., 2001
- Not checked yetcites Gortz et al., 2008
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“The deficits appear to be progressive with age, and at 12 months old the animals also show cognitive deficits in a reference memory version of the Barnes maze (Prut et al., 2007).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP23
What the sources say
- Not checked yetcites Prut et al., 2007
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The cognitive deficits in recognition memory do not appear as robust as those in working memory in this model as there are inconsistent reports in the literature (Dodart et al., 1999, 2002; Chen et al., 2000).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > PDAPP
What the sources say
- Not checked yetcites Dodart et al., 1999, 2002
- Not checked yetcites Chen et al., 2000
Strength:hedged· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“It should be noted that most of the AD mouse models are representative of the familial form of AD (FAD) which accounts for only a small percentage of the total AD cases each year (Campion et al., 1999).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models
What the sources say
- Not checked yetcites Campion et al., 1999
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Impairments in reference memory develop by 6 months and persist through the rest of the life of this model (Reiserer et al., 2007; Bernardo et al., 2009; O'leary and Brown, 2009).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP/PS1
What the sources say
- Not checked yetcites Reiserer et al., 2007
- Not checked yetcites Bernardo et al., 2009 source
- Not checked yetcites O'leary and Brown, 2009
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Cognitive deficits are first seen at 3 months of age in the RAWM spatial working memory task and are also reported by 6 months of age in the MWM (Cao et al., 2007; Ding et al., 2008).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP/PS1
What the sources say
- Not checked yetcites Cao et al., 2007
- Not checked yetcites Ding et al., 2008
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“However, they do not appear to progress with the age of the animal and there has even been a report of no recognition memory deficits in old animals in advanced stages of the disease (Karl et al., 2012).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > J20
What the sources say
- Not checked yetcites Karl et al., 2012
Strength:hedged· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These working memory deficits are followed temporally with the development of associative learning impairment in fear conditioning (Ohno et al., 2006; Devi and Ohno, 2010) as well as the development of deficits in a working memory version of the Y-maze (Oakley et al., 2006; Devi and Ohno, 2012; Shukla et al., 2013).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > 5×FAD
What the sources say
- Not checked yetcites Ohno et al., 2006
- Not checked yetcites Devi and Ohno, 2010
- Not checked yetcites Oakley et al., 2006
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“The APP/PS1 knock-in mouse model (first described in Flood et al., 2002) uses endogenous promoters to drive the expression of humanized amyloid beta sequence, and AD-like pathology and cognitive deficits develop in the absence of APP or PS1 overexpression (Flood et al., 2002).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP/PS1 KI
What the sources say
- Not checked yetcites Flood et al., 2002
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“The first observable deficits in this model are shown in associative learning and present themselves between 4 and 5 months of age (Dineley et al., 2002).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP + PS1
What the sources say
- Not checked yetcites Dineley et al., 2002
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These deficits are followed by impairments in associative memory (appearing by 14 months of age Thibault et al., 2012) and in recognition memory (not developing until 15 months of age Webster et al., 2013).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of the cognitive deficits seen in the commonly used AD mouse models > APP/PS1 KI
What the sources say
- Not checked yetcites Thibault et al., 2012
- Not checked yetcites Webster et al., 2013
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“Indeed, these non-cognitive symptoms are seen as a very important concern among the family members of the patients and caregivers alike (Tan et al., 2005).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models
What the sources say
- Not checked yetcites Tan et al., 2005
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These non-cognitive symptoms are often more difficult to deal with, as they compose important sources of distress and psychological burden on the family members/caregivers and can drastically affect the quality of life of patients by leading to institutionalization (Hope et al., 1998; Shin et al., 2005).”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models
What the sources say
- Not checked yetcites Hope et al., 1998
- Not checked yetcites Shin et al., 2005
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“This suggests that perhaps aggressive deficits correlate best with moderate to severe stages of the disease, which is also what is observed clinically in human AD”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Aggressive behaviors
What the sources say
- Not checked yetcites Senanarong et al., 2004
Strength:hedged· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Numerous meta-analysis studies have linked depression and AD”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Depressive symptoms
What the sources say
- Not checked yetcites Chen et al., 1999
- Not checked yetcites Charlson and Peterson, 2002
- Not checked yetcites Ownby et al., 2006
Strength:boosted· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“These disturbances are characterized by the AD patient's propensity to frequently awaken during the nighttime and to increase the amount of time slept during the day”
§ Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models > Temporal progression of AD-like non-cognitive behavioral abnormalities seen in the commonly used mouse models > Circadian rhythm and sleep disruptions
What the sources say
- Not checked yetcites Ancoli-Israel et al., 1989 source
- Not checked yetcites Okawa et al., 1991
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.

61 of 61

The paper relies on this without support.
No animal model recapitulates the entirety of AD in humans.
“However, no animal model recapitulates the entirety of AD in humans, and therefore it is important to understand both the utility and limitations of particular animal models.”
The paper relies on this without support.
Outside of frontotemporal lobar degeneration (FTLD), one does not see widespread cortical NFTs without abundant plaque pathology.
“It should be noted that outside of frontotemporal lobar degeneration (FTLD), one does not see widespread cortical NFTs without abundant plaque pathology.”
The paper relies on this without support.
During late stages (Braak stage V–VI), NFTs increase in number and manifest in neocortical areas responsible for higher cognitive domains such as executive function, visuospatial capacities, and speech in synchrony with observed AD-related cognitive deficits in these respective cognitive domains.
“During the late stages (Braak stage V–VI), NFTs increase in number and manifest in neocortical areas responsible for higher cognitive domains such as executive function, visuospatial capacities, and speech in synchrony with observed AD-related cognitive deficits in these respective cognitive domains.”
The paper relies on this without support.
Some of the earliest neuropathological changes in AD are in the hippocampus and entorhinal cortex, followed by changes in the medial temporal lobe.
“Some of the earliest neuropathological changes in AD are in the hippocampus and entorhinal cortex, followed by changes in the medial temporal lobe.”
The paper relies on this without support.
Neuropsychological assessment is the most reliable means to clinically evaluate the cognitive deficits seen in humans.
“Neuropsychological assessment is the most reliable means to clinically evaluate the cognitive deficits seen in humans.”
The paper relies on this without support.
Other cognitive domains impaired in human AD such as those involving language (i.e., verbal acuity tasks and verbal recall tasks) simply cannot be modeled in rodent models.
“Other cognitive domains impaired in human AD such as those involving language (i.e., verbal acuity tasks and verbal recall tasks) simply cannot be modeled in rodent models.”
The paper relies on this without support.
Working memory is perhaps one of the most well modeled aspects of the memory deficits in AD.
“Working memory is perhaps one of the most well modeled aspects of the memory deficits in AD.”
The paper relies on this without support.
As the patient moves from the preclinical phase of AD into MCI, more cognitive domains begin to be affected.
“As the patient moves from the preclinical phase of AD into MCI, more cognitive domains begin to be affected.”

8 of 8

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

“Mini-mental state”
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282
The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment
Nasreddine, Z. S., Phillips, N. A., Bédirian, V., Charbonneau, S., Whitehead, V., Collin, I., Cummings, J. L., & Chertkow, H. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.53221.x · Cited by 25,553
The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657 · cited 1×
“Once the AD patient progresses past MCI and into dementia, general cognition continues to decline with deﬁcits appearing in all respective cognitive domains (Huff et al., 1987; Locascio et al., 1995; Lambon Ralph et al., 2003; Mckhann et al., 2011).”
Background
Place navigation impaired in rats with hippocampal lesions
Morris, R. G. M., Garrud, P., Rawlins, J. N. P., & O'Keefe, J. (1982) · Nature · doi:10.1038/297681a0 · Cited by 6,340 · cited 8×
“In this model, the cognitive deﬁcits ﬁrst present themselves in spatial working memory at 4 months of age when assessed by MWM testing (Hartman et al., 2005).”
MethodInfluential
Boston Naming Test
Kaplan, E., Goodglass, H., Weıntraub, S., & Segal, O. (2001) · Medical Entomology and Zoology · Cited by 4,378
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210 · cited 6×
“(Promoter: Hamster PrP Promoter, Symbol: Tg (APPSWE) 2576Kha, MGI ID: 2385631) In the Tg2576 mouse (Hsiao et al., 1996), the ﬁrst presentation of cognitive deﬁcits is seen at 5 months of age in spatial working memory (Arendash et al., 2004).”
BackgroundMethodInfluential
A new rating scale for Alzheimer's disease
(1984) · American Journal of Psychiatry · doi:10.1176/ajp.141.11.1356 · Cited by 4,175 · cited 1×
“The Alzheimer’s Disease Assessment Scale (ADAS) was specifically developed to measure the severity of symptoms commonly seen in AD (Rosen et al., 1984).”
Method
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part I. Clinical and neuropsychological assesment of Alzheimer's disease
Moms, J. C., Heyman, A., Mohs, R. C., Hughes, J. P., van Belle, G., Fillenbaum, G., Mellits, E. D., & Clark, C. (1989) · Neurology · doi:10.1212/wnl.39.9.1159 · Cited by 4,130 · cited 1×
“…tests are extensively used as clinical diagnostic tools (Schmitt, 1994) as well as to track the progression of the disease (Flicker et al., 1984; Morris et al., 1989; Storandt and Hill, 1989; Storandt, 1991; Welsh et al., 1991, 1992; Locascio et al., 1995; Albert, 1996; Storandt et al., 1998;…”
Method
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126 · cited 1×
“…2006), 25: (Ohno et al., 2006), 26: (Shukla et al., 2013), 27: (Devi and Ohno, 2010), 28:(Devi and Ohno, 2012), 29: (Urano and Tohda, 2010), 30: (Oddo et al., 2003), 31: (Clinton et al., 2007), 32: (Carroll et al., 2007), 33: (Gimenez-Llort et al., 2007), 34: (Billings et al., 2005), 35:…”
The Association Between Quantitative Measures of Dementia and of Senile Change in the Cerebral Grey Matter of Elderly Subjects
Blessed, G., Tomlinson, B. E., & Roth, M. (1968) · British Journal of Psychiatry · doi:10.1192/bjp.114.512.797 · Cited by 4,117 · cited 1×
“There have been numerous clinicopathological studies attempting to correlate amyloid plaques with the cognitive deﬁcits seen in AD (Blessed et al., 1968; Tomlinson et al., 1970; Duyckaerts et al., 1990, 1998; Berg et al., 1998; Gold et al., 2000; Mungas et al., 2001; Tiraboschi et al., 2002, 2004;…”
Background

Flagged first, then by citations

Show all 365 references

Research works printed but not linked: 2

Benedict, 1994, Preliminary standardization and validation of a multiple-form test for the assessment of visuospatial memory, Arch. Clin. Neuropsychol, 9, 109
Benton, 1992, Benton Visual Retention Test, 5th Edn

Sorted by citations

Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,312
The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice
Kraeuter, A.-K., Guest, P. C., & Sarnyai, Z. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8994-2_10 · Cited by 1,451
Alzheimer's disease: experimental models and reality
Drummond, E., & Wisniewski, T. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1662-x · Cited by 810
“There have been many clinicopathological studies that have correlated amyloid plaques with cognitive deficits in AD, with an emerging picture that the strongest correlation exists in the earliest stages of the disease and this association greatly weakens as NFTs and neocortical degeneration become more widespread [9,…”
Background
APP mouse models for Alzheimer’s disease preclinical studies.
Sasaguri, H., Nilsson, P., Hashimoto, S., Nagata, K., Saito, T., De Strooper, B., Hardy, J., Vassar, R., Winblad, B., & Saido, T. C. (2017) · The EMBO Journal · doi:10.15252/embj.201797397 · Cited by 793
“Apart from potential overexpression artifacts, it has been difficult to standardize the phenotypes of the various models because of their construction with different promoters, transgene constructs, and mouse strains (Webster et al , 2014; Foley et al , 2015).”
The case for rejecting the amyloid cascade hypothesis
Herrup, K. (2015) · Nature Neuroscience · doi:10.1038/nn.4017 · Cited by 768

See all 755

Authors: Webster, S. J., Bachstetter, A. D., Nelson, P. T., Schmitt, F. A., & Van Eldik, L. J.
Affiliations: University of Kentucky (US)
ORCID: Bachstetter, Adam D.
Nelson, Peter T.
Schmitt, Frederick A.
Venue: Frontiers in Genetics
Publisher: Frontiers Media SA
Published: 2014-04-23
Volume: 5
Pages: 88-88
ISSN: 1664-8021 (ISSN-L)
DOI: 10.3389/fgene.2014.00088
PMC: PMC4005958
OpenAlex: W1982313782
Semantic Scholar: 6bbaedb9f24f173e0fcdb0d6b5b0bfe9eb3f4679
Cited by: 755
References: 365
Citations by year: 2026: 36 · 2025: 51 · 2024: 60 · 2023: 72 · 2022: 64 · 2021: 57 · 2020: 63 · 2019: 63 · 2018: 79 · 2017: 71 · 2016: 76 · 2015: 48 · 2014: 14
FWCI: 8.15
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Genetics (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institutes of Health
National Institute on Aging (P30AG028383)
National Institute of Nursing Research
National Institute of Child Health and Human Development
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: Alzheimer's disease, mouse models of Alzheimer's disease, amyloid precursor protein mutations, APP/PS1 mice, PDAPP mice, Tg2576 mice, APP23 mice, TgCRND8 mice, 5xFAD mice, 3xTg-AD mice, behavioral tests, cognitive impairment, spatial memory, recognition memory, associative learning, attention, set-shifting, reversal learning, neuropsychological assessment

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

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Using mice to model Alzheimer's dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models

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