Cited by 385Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsHistorical and Modern Theater Studies

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Distinguishing Alzheimer’s disease from other major forms of dementia

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Karantzoulis, Stella, Galvin, James E·2011·Expert Review of Neurotherapeutics

DOI 10.1586/ern.11.155PMC PMC3225285

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Abstract

Alzheimer's disease (AD) is the most common and most studied cause of dementia. Significant advances have been made since the first set of clinical criteria for AD were put forth in 1984 that are now captured in the new criteria for AD published in 2011. Key features include recognition of a broad AD spectrum (from preclinical to mild cognitive impairment to AD dementia) and requirement of AD biomarkers for diagnosis. Correctly diagnosing dementia type is increasingly important in an era when potential disease-modifying agents are soon to be marketed. The typical AD dementia syndrome has at its core, an amnestic syndrome of the hippocampal type, followed by associated deficits in word-finding, spatial cognition, executive functions and neuropsychiatric changes. Atypical presentations of AD have also been identified that are presumed to have a different disease course. It can be difficult to distinguish between the various dementia syndromes given the overlap in many common clinical features across the dementias. The clinical difficulty in diagnosis may reflect the underlying pathology, as AD often co-occurs with other pathologies at autopsy, such as cerebrovascular disease or Lewy bodies. Neuropsychological evaluation has provided clinicians and researchers with profiles of cognitive strengths and weaknesses that help to define the dementias. There is yet no single behavioral marker that can reliably discriminate AD from the other dementias. The combined investigation of cognitive and neurobehavioral symptoms coupled with imaging markers could provide a more accurate approach for differentiating between AD and other major dementia syndromes in the future.

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“, 2011), and other degenerative dementias (Karantzoulis and Galvin, 2011; Lopez et al., 2011).”
Background
Effect of Hypertension Duration and Blood Pressure Control During Early Adulthood on Cognitive Function in Middle Age
Zhou, H., Zhu, Z., Liu, C., Bai, Y., Zhan, Q., Huang, X., Zeng, Q., Ren, H., & Xu, D. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-215070 · Cited by 15
“…typical Alzheimer’s disease syndrome can be characterized by prominent episodic memory impairment, with secondary deﬁcits in executive functions, while vascular dementia is associated with primary deﬁcits in information processing speed and executive functions, and secondary deﬁcits in memory [28].”
The ecological validity of the Uniform Data Set 3.0 neuropsychological battery in individuals with mild cognitive impairment and dementia
Benge, J. F., Artz, J. D., & Kiselica, A. M. (2020) · The Clinical Neuropsychologist · doi:10.1080/13854046.2020.1837246 · Cited by 15
“…visual and verbal delayed free recall and rapid visuomotor search and sequencing as indexed by Trail Making Tests A&B. Individuals with presumed Alzheimer’s disease tend to demonstrate problems with memory and executive functions (Karantzoulis & Galvin, 2011; Saxton, Smith, & Boller, 1991).”
Method
Hypoglycemic TCM formulas (Huangqi-Gegen drug pair) have the potential as an Alzheimer's disease
Yang, H. T., Ren, K., Hou, W.-Q., Cao, H.-S., Zhang, Y.-R., Li, Z.-M., Wang, S., Yang, W., & Liu, D. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155723 · Cited by 14
Biomarcadores en la enfermedad de Alzheimer
Ribas, G. G., López-Sendón, J. L., & Caldentey, J. G. (2014) · Revista de Neurología · doi:10.33588/rn.5807.2013394 · Cited by 14
Exercise priming with transcranial direct current stimulation: a study protocol for a randomized, parallel-design, sham-controlled trial in mild cognitive impairment and Alzheimer’s disease
Liu, C. S., Herrmann, N., Song, B. X., Ba, J., Gallagher, D., OH, P. I., Marzolini, S., Rajji, T. K., Charles, J., Papneja, P., et al. (2021) · BMC Geriatrics · doi:10.1186/s12877-021-02636-6 · Cited by 15
“The earliest and most common clinical manifestation involves episodic memory impairment and a diminished ability to encode new material into long-term memory [4].”
Background
Predicting explainable dementia types with LLM-aided feature engineering
Kashyap, A. M., Rao, D., Boland, M. R., Shen, L., & Callison-Burch, C. (2025) · Bioinformatics · doi:10.1093/bioinformatics/btaf156 · Cited by 16
“Karantzoulis and Galvin (2011) mention that semantic fluency is comparatively better preserved in Vascular Dementia compared to Alzheimer’s Dementia, supporting our results for poor performance on semantically based tasks being a negative predictive feature for Vascular Dementia and profound loss…”
ROCK and PDE-5 Inhibitors for the Treatment of Dementia: Literature Review and Meta-Analysis
Lee, D.-H., Lee, J. Y., Hong, D.-Y., Lee, E. C., Park, S.-W., Jo, Y. N., Park, Y. J., Cho, J. Y., Cho, Y. J., Chae, S. H., et al. (2022) · Biomedicines · doi:10.3390/biomedicines10061348 · Cited by 13
“VD also exhibits mild cognitive impairment, acute or subacute progressive cognitive impairment, depending on severity, and is often accompanied by AD [12].”
Background
ACE Alzheimer’s: The Role of Vitamin A, C and E (ACE) in Oxidative Stress induced Alzheimer’s Disease
Mehta, V., Desai, N., Pervez, A., Nemade, D., Dawoodi, S. L., & Zaman, S. B. (2017) · Journal of Medical Research and Innovation · doi:10.15419/jmri.86 · Cited by 14
“It has been observed that Vitamin A prevents the formation of betaamyloid plaques!.([31]) Similarly, Vitamins C and E have also been proven to be beneficial in preventing/delaying the progression to irreversible neurocognitive decline.”
Background
Evaluation of an Aβ1–40-induced cognitive deficit in rat using a reward-directed instrumental learning task
Shi, Z., Sun, X., Liu, X., Chen, S., Chang, Q., Chen, L., Song, G., & Li, H. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.07.006 · Cited by 13
Behavioral and Psychological Symptoms of Dementia
Wu, S., & Yu, R. (2020) · Springer eBooks · doi:10.1007/978-3-319-69892-2_823-1 · Cited by 13
An in-silico insight into the predictive interaction of Apolipoprotein-E with Epstein-Barr virus proteins and their probable role in mediating Alzheimer’s disease
Tiwari, D., Srivastava, G., Indari, O., Tripathi, V. S., Siddiqi, M. I., & Jha, H. C. (2022) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2022.2138978 · Cited by 12
Advancements in nose-to-brain drug targeting for Alzheimer’s disease: a review of nanocarriers and clinical insights
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“In AD, neuronal degeneration causes significant cognitive impairment, thinking, and decision-making (Karantzoulis and Galvin 2011).”
Will Posttranslational Modifications of Brain Proteins Provide Novel Serological Markers for Dementias?
Wang, Y., Sørensen, M. G., Zheng, Q., Zhang, C., Karsdal, M. A., & Henriksen, K. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/209409 · Cited by 13
“Several types of dementia exist, with Alzheimer’s disease (AD) being the most prominent, followed by dementia with Lewy bodies (DLB), frontotemporal dementia (FTD) also known as frontotemporal lobar degeneration (FTLD), corticobasal degeneration (CBD), and vascular dementia (VaD) [1].”
Background
The role of the cellular prion protein in the uptake and toxic signaling of pathological neurodegenerative aggregates
Scialò, C., & Legname, G. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.08.008 · Cited by 12
Translating state-of-the-art brain magnetic resonance imaging (MRI) techniques into clinical practice: multimodal MRI differentiates dementia subtypes in a traditional clinical setting
Kuhn, T. P., Becerra, S. A., Duncan, J., Spivak, N. M., Dang, B. H., Habelhah, B., Mahdavi, K. D., Mamoun, M. S., Whitney, M., Pereles, F. S., et al. (2021) · Quantitative Imaging in Medicine and Surgery · doi:10.21037/qims-20-1355 · Cited by 12
“Differentiating the neurocognitive disorders that arise from these diseases is imprecise and confounded by overlapping pathological biomarkers (2,3).”
Background
Genetic Markers in Biological Fluids for Aging-Related Major Neurocognitive Disorder
Castro-Chavira, S. A., Fernández, T., Nicolini, H., Díaz-Cintra, S. Y., & Prado-Alcalá, R. A. (2015) · Current Alzheimer Research · doi:10.2174/1567205012666150302155138 · Cited by 13
“, hippocampus and entorhinal cortex) and, as the disease progresses, extend to association areas in temporal, parietal, and frontal cortices [11].”
Influential
Suicide and Lewy body dementia: Report of a Lewy body dementia association working group
Armstrong, M. J., Sullivan, J. L., Amodeo, K., Lunde, A. M., Tsuang, D. W., Reger, M. A., Conwell, Y., Ritter, A. R., Bang, J., Onyike, C. U., et al. (2020) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.5462 · Cited by 14
“atric comorbidities are common, and executive function is frequently affected.(48,49) Whether the method by which the dementia diagnosis was provided contributes to suicide risk is uncertain.”
Background
Quantitative Longitudinal Predictions of Alzheimer’s Disease by Multi-Modal Predictive Learning
Prakash, M., Abdelaziz, M., Zhang, L., Strange, B. A., Tohka, J., & Initiative, A. D. N. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-200906 · Cited by 11
“A clinical diagnosis of AD is currently a challenge due to a lack of clear diagnostic markers of AD and overlapping clinical features with other dementia types [13, 14].”
Exploring new 5‐Nitroimidazole Derivatives as Potent Acetylcholinesterase and Butyrylcholinesterase Enzyme Inhibitors
Gürsoy, Ş., Satici, D., Kuzu, B., Türkmenoğlu, B., Dilek, E., & Algül, Ö. (2024) · Chemistry & Biodiversity · doi:10.1002/cbdv.202400918 · Cited by 11
Chiral thioureas containing naphthalene moiety as selective butyrylcholinesterase inhibitors: Design, synthesis, cholinesterase inhibition activity and molecular docking studies
Karaküçük‐İyidoğan, A., Sıcak, Y., Uysal, D. B., Taşkın‐Tok, T., Öztürk, M., & Oruç‐Emre, E. E. (2024) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2024.139333 · Cited by 11
Artificial intelligence in drug development for delirium and Alzheimer’s disease
Ai, R., Xiao, X., Deng, S., Yang, N., Xing, X., Watne, L. O., Selbæk, G., Wedatilake, Y., Xie, C., Rubinsztein, D. C., et al. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.04.026 · Cited by 11
“Risk factors include a range of stressors, such as alcohol use, infection, depression, malnutrition, medications and environment changes, as well as conditions such as hip fracture and severe COVID-19 4-6 .”
Informant report of practical judgment ability in a clinical sample of older adults with subjective cognitive decline, mild cognitive impairment, and dementia
Rabin, L. A., Quinn, C. G., Nester, C. O., Ellis, L., & Paré, N. (2021) · Aging Neuropsychology and Cognition · doi:10.1080/13825585.2020.1859081 · Cited by 11
“…the lowest level of judgment problems reported for the SCD group, followed by MCI, AD/AD+VaD, VaD, and bvFTD, consistent with overall levels of objective impairment and specific deficits in executive functions in these patient groups (Elderkin-Thompson et al., 2004; Karantzoulis & Galvin, 2011).”
Result
Dimethyl Fumarate Alleviates Adult Neurogenesis Disruption in Hippocampus and Olfactory Bulb and Spatial Cognitive Deficits Induced by Intracerebroventricular Streptozotocin Injection in Young and Aged Rats
Kurowska, E., Ruciński, J., Myślińska, D., Grembecka, B., Wrona, D., & Majkutewicz, I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415449 · Cited by 12
“, frontotemporal dementia, vascular dementia), which significantly complicates and delays diagnosis [2,3].”
Background
Communication interventions for people with dementia and their communication partners
El‐Wahsh, S., Monroe, P., Kumfor, F., & Ballard, K. J. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818685-5.00003-9 · Cited by 11
Detection of plasma Aβ seeding activity by a newly developed analyzer for diagnosis of Alzheimer’s disease
Jia, J., Li, T., Yang, J., Chen, B., Qin, W., Wei, C., Song, Y., Wang, Q., Li, Y., & Jia, L. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-00964-2 · Cited by 10
“Note that the differential diagnosis of AD among other dementias is difficult using clinical testing [19].”
Background
Converging links between adult-onset neurodegenerative Alzheimer’s disease and early life neurodegenerative neuronal ceroid lipofuscinosis?
Hermey, G., & Klein, M. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.361544 · Cited by 10
“These are complex considering that other dementia syndromes can mimic AD at the time of the initial evaluation, there is yet no single behavioral marker that can reliably discriminate AD from other dementias and AD often co-occurs with other pathologies at autopsy (Karantzoulis and Galvin, 2011).”
Background
Investigation of Potential Drug Targets for Cholesterol Regulation to Treat Alzheimer’s Disease
Passero, M., Zhai, T., & Huang, Z. J. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20136217 · Cited by 10
“It is the most common cause of dementia and is difficult to diagnose due to the fact that many of the symptoms are similar to the normal effects of aging [3].”
Background
Mouse model of Alzheimer's disease demonstrates differential effects of early disease pathology on various brain regions
Deng, L., Gupta, V., Wu, Y., Pushpitha, K., Chitranshi, N., Gupta, V. B., Fitzhenry, M. J., Zabet‐Moghaddam, M., Karl, T., Salekdeh, G. H., et al. (2021) · PROTEOMICS · doi:10.1002/pmic.202000213 · Cited by 10
“The disease progressively affects memory formation and its retrieval processes in the brain which gradually extends to visuospatial, language, attention, logic, and executive function deficits [6].”
Background
Cerebral Blood Flow in Alzheimer’s Disease: A Meta-Analysis on Transcranial Doppler Investigations
Zuin, M., Vito, A. D., Romagnoli, T., Polastri, M., Capatti, E., Azzini, C., Brombo, G., & Zuliani, G. (2024) · Geriatrics · doi:10.3390/geriatrics9030058 · Cited by 9
“Alzheimer’s disease (AD) represents the most common type of dementia, affecting >45 million people worldwide [1].”
Background
A Framework for Best Practices and Readiness in the Advent of Anti-Amyloid Therapy for Early Alzheimer’s Disease in Asia
Lee, J. H., Jia, J., Ji, Y., Kandiah, N., Kim, S., Mok, V., Pai, M., Senanarong, V., Suh, C. H., & Chen, C. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-240684 · Cited by 9
Electroencephalography in young onset dementia
Brown, C. W., Chen, H.-Y., & Panegyres, P. K. (2023) · BMC Neurology · doi:10.1186/s12883-023-03248-w · Cited by 9
“This was an expected result, as Alzheimer’s disease typically begins as a decline in memory, and frontotemporal dementia as a change in behaviour or personality [61].”
Background
The Changing Profile of Patients in a Geriatric Medicine Led Memory Clinic over 12 Years
Chua, X. Y., Ha, N. H. L., Cheong, C. Y., Wee, S. L., & Yap, P. L. K. (2019) · The journal of nutrition health & aging · doi:10.1007/s12603-019-1161-6 · Cited by 9
An Overview of Existing Publications and Most Relevant Projects/Platforms on the Use of Blockchain in Medicine and Neurology
Hort, J., Vališ, M., Zhang, B., Kuča, K., & Angelucci, F. (2021) · Frontiers in Blockchain · doi:10.3389/fbloc.2021.580227 · Cited by 9
“There are various forms of dementia, which are in turn characterized by various states of illness (Karantzoulis and Galvin, 2011).”
Background
In vitro and in vivo biological evaluation of newly synthesized multi-target 20(R)-panaxadiol derivatives for treating Alzheimer's disease
Pang, L., Li, J., Liu, Z., Quan, Y., Sui, H., Jia, Y., Chen, F., Lee, J. J., Liu, P., Quan, Z., et al. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114825 · Cited by 9
Exploring the Regulatory Landscape of Dementia: Insights from Non-Coding RNAs
Kim, J.-M., Kim, W. R., Park, E. G., Lee, D. H., Lee, Y. J., Shin, H. J., Jeong, H.-S., Roh, H.-Y., & Kim, H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25116190 · Cited by 8
“In in vitro [126] N/A: not available.”
Evaluation of antioxidant, acetylcholinesterase, lipase, α-amylase, xanthine oxidase, and α-glucosidase enzyme inhibitory activities of Sri Lankan tea cultivars
Piyasena, K. G. N. P., Ranatunga, M. A. B., Napagoda, M. T., Amarasinghe, N. R., Abayarathne, A. A. B., & Jayasinghe, L. (2025) · Discover Plants. · doi:10.1007/s44372-025-00122-6 · Cited by 8
“Furthermore, the ability of tea polyphenolic compounds to impede the hydrolysis of disaccharides and regulate blood glucose has also been documented [30].”
Shared genes and pathways in dementia: Insights from genome‐wide association studies
Loi, K. J., Radtke, N., Kiriluk, C., Noureldein, M. H., Feldman, E. L., Bakulski, K. M., & Chen, K. S. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70845 · Cited by 8
“3,4 However, these dementia subtypes also share pathophysiologic pathways and overlapping clinical presentations, suggesting potential common or related underlying genetic cues that contribute to disease development.”
Molecular mechanisms of aging in the pathogenesis of Alzheimer’s disease
Kakkar, A., Singh, H., Singh, B. K., Chauhan, K., Chopra, S., Chopra, H., & Mishra, A. K. (2026) · Discover Neuroscience · doi:10.1186/s13064-026-00243-y · Cited by 9
“Historically, during the 1980s, dementias were largely regarded as clinical syndromes attributed to a single, prototypical manifestation of AD [43].”
Beneficial Effect of Brassica nigra Fixed Oil on The Changes in Memory Caused by Β-Amyloid in an Animal Model
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“Dementia can be caused by various factors, with Alzheimer’s disease (AD) being known as the most common reason.(1) Although there are a wide range of reasons for the onset and progression of AD,(2) the β-amyloid (Aβ) 42 cascade hypothesis has”
Background
The Relationship Between Prior Cancer Diagnosis and All-Cause Dementia Progression Among US Adults
Fowler, M. E., Wright, N. C., Triebel, K. L., Rocque, G. B., Irvin, M. R., & Kennedy, R. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220054 · Cited by 9
“However, chart notes provided clarity on underlying subtype, which is important given pathological and cognitive differences among dementia subtypes [1, 25].”
Centella asiatica, an Ayurvedic Medicinal Plant, Prevents the Major Neurodegenerative and Neurotoxic Mechanisms Associated with Cognitive Impairment
Ahuja, M., Patel, M., Majrashi, M., Mulabagal, V., & Dhanasekaran, M. (2017) · Medicinal and aromatic plants of the world · doi:10.1007/978-981-10-5978-0_1 · Cited by 9
The Role of Th17 Cells in Immunopathogenesis of Neuroinflammatory Disorders
Pourgholaminejad, A., & Tahmasebinia, F. (2019) · Contemporary clinical neuroscience · doi:10.1007/978-3-030-19515-1_3 · Cited by 8
Reducing safety risk among underserved caregivers with an Alzheimer's home safety program
Levy‐Storms, L., Cherry, D., Lee, L. J., & Wolf, S. M. (2016) · Aging & Mental Health · doi:10.1080/13607863.2016.1181710 · Cited by 8
“While other forms of dementia exist, they have different symptoms and timing of progression to later stages (Karantzoulis & Galvin, 2011).”
Background

Authors: Karantzoulis, S., & Galvin, J. E.
Affiliations: NYU Langone Health (US)
Corresponding author: Karantzoulis, Stella
ORCID: Karantzoulis, Stella
Galvin, James E
Venue: Expert Review of Neurotherapeutics
Publisher: Informa UK Limited
Published: 2011-11
Volume: 11
Issue: 11
Pages: 1579-1591
ISSN: 1473-7175 (ISSN-L)
1744-8360
DOI: 10.1586/ern.11.155
PMC: PMC3225285
OpenAlex: W2067203120
Cited by: 385
References: 118
Citations by year: 2026: 24 · 2025: 48 · 2024: 38 · 2023: 32 · 2022: 30 · 2021: 42 · 2020: 38 · 2019: 26 · 2018: 26 · 2017: 28 · 2016: 14 · 2015: 11 · 2014: 11 · 2013: 11 · 2012: 6
FWCI: 6.16
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Expert Review of Neurotherapeutics (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (AG008051, P30AG008051, R01AG040211)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Social Sciences › Psychology › Clinical Psychology › Historical and Modern Theater Studies
Keywords: Alzheimer's disease, dementia diagnosis, differential diagnosis of dementia, biomarkers, mild cognitive impairment, amnestic syndrome, atypical Alzheimer's disease, neuropsychological assessment, neuroimaging biomarkers, Lewy bodies, cerebrovascular disease, disease-modifying agents
MeSH terms: Alzheimer Disease, Dementia, Diagnosis, Differential, Humans, Neuropsychological Tests

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Distinguishing Alzheimer’s disease from other major forms of dementia

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