Hippocampal neurons in pre-clinical Alzheimer's disease.

In the paper

“The validity of the concept of a preclinical stage in AD is supported by longitudinal clinical studies of mild memory changes followed by an accelerated decline [6,15,19,33] and by clinical-pathological studies that report the presence of the characteristic lesions of AD in cognitively normal individuals [1,23,35,36].”

What the sources say

• ?Not checked — no full text of the sourcecites [6] Elias, 2000, The preclinical phase of Alzheimer disease: a 22-year prospective study of the Framingham Cohort, Arch. Neurol. source
• ?Not checked — no full text of the sourcecites [15] Jacobs, 1995, Neuropsychological detection and characterization of preclinical Alzheimer’s disease, Neurology source
• ?Not checked — no full text of the sourcecites [19] Masur, 1994, Neuropsychological prediction of dementia and the absence of dementia in healthy elderly persons, Neurology source
• ?Not checked — no full text of the sourcecites [33] Small, 2000, The course of cognitive impairment in preclinical Alzheimer disease: 3- and 6-year follow-up of a population-based sample, Arch. Neurol. source
• ?Not checked — no full text of the sourcecites [1] Arriagada, 1992, Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer’s disease, Neurology source
• ?Not checked — no full text of the sourcecites [23] Morris, 1996, Cerebral amyloid deposition and diffuse plaques in “normal” aging: evidence for presymptomatic and very mild Alzheimer’s disease, Neurology source
• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [35] Troncoso, 1996, Neuropathology in controls and demented subjects from the Baltimore Longitudinal Study of Aging, Neurobiol. Aging source
• Partly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [36] Troncoso, 1998, Neuropathology of preclinical and clinical late-onset Alzheimer’s disease, Ann. Neurol. sourceExperimental — accuracy not yet measured

In the paper

“Some of these studies suggest that the A␤ deposits in the brain may precede the onset of cognitive decline by a decade or more [27,36], indicating the presence of a wide temporal window for neuronal protective therapeutic intervention.”

What the sources say

• ?Not checked — no full text of the sourcecites [27] Sandberg, 2001, The prevalence of the neuropathological lesions of Alzheimer’s disease is independent of race and gender, Neurobiol. Aging source
• Supported

  The Discussion (page not specified in our copy) says that perineuronal Aβ deposition is an early event that precedes clinical onset by several decades. It also identifies these early abnormalities as having therapeutic implications, supporting the citing sentence’s proposed intervention window. (LLM, conf=0.89)

  cites [36] Troncoso, 1998, Neuropathology of preclinical and clinical late-onset Alzheimer’s disease, Ann. Neurol. source

In the paper

“However, no differences in neuron number were present between these two groups in either the granule or the CA2-3 subdivision.”

In the paper

“With regard to gender composition and severity of disease, the AD group examined in the present study differs from the sample used in our previous study.”

In the paper

“Whereas in our original study, all the AD cases were males and in the later stages of the disease, in the present study half of the cases were females and 5 out of 14 cases were of mild to moderate severity, i.e., with MMSE > 16.”

In the paper

“Although our study had limited power to detect a difference in the number of hippocampal neurons between controls and preclinical AD cases, it should be underscored that the agreement of our observations with those of a previous study [26], also with limited statistical power, strengthens the findings in both.”

What the sources say

• ?Not checked — no full text of the sourcecites [26] Price, 2001, Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer’s disease, Arch. Neurol. source

In the paper

“The optical fractionator was chosen for the present study in order to reduce potential biases related to defining the anatomical borders of regions of interest.”

In the paper

“This is a distinct possibility since the clinical data in that report was retrospective and it is not clear if the clinical evaluations were designed to detect changes in mental status or cognitive decline.”

In the paper

“The AD (n = 14) subjects had clinical histories of dementia and their brains contained a sufficient number of neuritic A␤ plaques (CERAD plaques scores B or C) to meet the CERAD criteria for definite AD [21].”

What the sources say

• ?Not checked — no full text of the sourcecites [21] Mirra, 1991, The consortium to establish a registry for Alzheimer’s disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease, Neurology source

In the paper

“The clinical diagnosis was made without knowledge of the pathologic diagnosis.”

In the paper

“The relatively mild clinical severity of the disease in the male AD cases, together with the large variability in the preclinical group and the reduction in the size of the groups when making comparisons among the males, may also be responsible for our inability to demonstrate significant differences in the number of hippocampal neurons between preclinical AD and AD groups (Table 4).”

In the paper

“The optical fractionator method [38] was used to estimate the total number of neurons in each hippocampal subdivision of each individual used in the study.”

What the sources say

• ?Not checked — no full text of the sourcecites [38] West, 1991, Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator, Anat. Rec. source

In the paper

“The neuropathological diagnosis of AD followed CERAD [21] guidelines.”

What the sources say

• ?Not checked — no full text of the sourcecites [21] Mirra, 1991, The consortium to establish a registry for Alzheimer’s disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease, Neurology source

In the paper

“In a previous study we described the pattern of loss of hippocampal neurons in normal aging and AD [39] and concluded that the most distinctive lesion of AD was the loss of neurons in the CA1 region.”

What the sources say

• ?Not checked — no full text of the sourcecites [39] West, 1994, Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease, Lancet source

In the paper

“However, another study [32] failed to show AD-related changes in CA1.”

What the sources say

• ?Not checked — no full text of the sourcecites [32] Simic, 1997, Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer’s disease, J. Comp. Neurol. source

In the paper

“This result may be explained by contamination of the age-matched control group with mild AD cases.”

In the paper

“The preclinical AD subjects (n = 8) were cognitively intact and their MMSE scores were ≥26, but their brains contained substantial numbers of neuritic A␤ plaques (CERAD plaque scores B or C) [21].”

What the sources say

• ?Not checked — no full text of the sourcecites [21] Mirra, 1991, The consortium to establish a registry for Alzheimer’s disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease, Neurology source

In the paper

“Silver stains were used to determine Braak neurofibrillary scores [4].”

What the sources say

• ?Not checked — no full text of the sourcecites [4] Braak, 1991, Neuropathological stageing of Alzheimer-related changes, Acta Neuropathol. source

In the paper

“The mean CEs, for the individual estimates made in each subdivision, were less than 0.10, indicating that the precision of the estimates derived with this sampling scheme were adequate for the stereological analysis described here [38].”

What the sources say

• ?Not checked — no full text of the sourcecites [38] West, 1991, Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator, Anat. Rec. source

In the paper

“The development of NFT and SP has been described in preclinical AD [25], but there is only a single stereological study of the number of neurons in the hippocampus in preclinical AD [26].”

What the sources say

• ?Not checked — no full text of the sourcecites [25] Price, 1999, Tangles and plaques in nondemented aging and “preclinical” Alzheimer’s disease, Ann. Neurol. source
• ?Not checked — no full text of the sourcecites [26] Price, 2001, Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer’s disease, Arch. Neurol. source

In the paper

“Moreover, we found that the degeneration in CA1 was disease-specific and not related to aging, per se.”

What the sources say

• ?Not checked — no full text of the sourcecites [39] West, 1994, Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease, Lancet source

In the paper

“The age-matched controls (n = 11) were cognitively intact and their MMSE were ≥26, and their brains had no or minimal pathologic changes that ranged from no A␤ deposits, to a few diffuse A␤ plaques, to sparse neuritic A␤ plaques (CERAD neuritic plaque score 0 or A).”

What the sources say

• ?Not checked — no full text of the sourcecites [21] Mirra, 1991, The consortium to establish a registry for Alzheimer’s disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease, Neurology source