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Distinguishing Alzheimer’s disease from other major forms of dementia
Open accessAbstract
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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“Clinicians face considerable difficulties identifying and differentiating between similar conditions, especially when symptoms frequently appear across many common diseases [124,125].”
From Toward Safer Diagnoses: A SEIPS-Based Narrative Review of Diagnostic Errors (2026) · cites this paper as [125]
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“While bvFTD patients may have mild difficulty with free recall early in the disease, recognition memory is typically intact and thus patients are able to recognize items with cueing, consistent with a retrieval-predominant deficit [24].”
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“…impact, first, word-finding abilities, category fluency, and verbal comprehension and, later as the disease progresses, speech content, and prosody (Karantzoulis & Galvin, 2011; Weiner & Lipton, 2009), which can lead to communication breakdowns during a variety of ADLs (Small, Geldart, & Gutman,…”
BackgroundSodhi, R. K., & Singh, N. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070487 · Cited by 49
“The typical dementia of AD type is characterized by prominent episodic memory impairment, with secondary deficits in word-finding skills, spatial cognition, executive functions and neuropsychiatric changes [1].”
BackgroundCause of Death and End‐of‐Life Experiences in Individuals with Dementia with Lewy Bodies
Armstrong, M. J., Slande Alliance, Corsentino, P., DeKosky, S. T., & Taylor, A. (2018) · Journal of the American Geriatrics Society · doi:10.1111/jgs.15608 · Cited by 48
Computational modelling of fluid and solute transport in the brain
Martinac, A. D., & Bilston, L. E. (2019) · Biomechanics and Modeling in Mechanobiology · doi:10.1007/s10237-019-01253-y · Cited by 49
“…in neurodegenerative disorders, such as the peptide amyloid beta ( Aβ ) (Bacyinski et al. 2017), a compound whose accumulation in the brain is associated with the most prevalent form of dementia, Alzheimer’s disease (Karantzoulis and Galvin 2011; Tarasoff-Conway et al. 2015; Simon and Iliff 2016).”
BackgroundThe Association Between Trace Elements Exposure and the Cognition in the Elderly in China
Gu, L., Yu, J., Fan, Y., Wang, S., Yang, L., Liu, K., Wang, Q., Chen, G., Zhang, D., Ma, Y., et al. (2020) · Biological Trace Element Research · doi:10.1007/s12011-020-02154-3 · Cited by 47
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Galetta, K. M., Chapman, K. R., Essis, M. D., Alosco, M. L., Gillard, D. M., Steinberg, E. G., Dixon, D. B., Martin, B. M., Chaisson, C. E., Kowall, N. W., et al. (2016) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000157 · Cited by 46
Chakraborty, A., Mohapatra, S. S., Barik, S., Roy, I., Gupta, B., & Biswas, A. (2023) · Bioscience Reports · doi:10.1042/bsr20220324 · Cited by 47
Galvin, J. E., Chrisphonte, S., Cohen, I., Greenfield, K. K., Kleiman, M. J., Moore, C., Riccio, M. L., Rosenfeld, A., Shkolnik, N., Walker, M. I., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12334 · Cited by 45
Self-citationA Review of Application of Aβ42/40 Ratio in Diagnosis and Prognosis of Alzheimer’s Disease
Xu, C., Zhao, L., & Dong, C. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220673 · Cited by 46
“As FTD and DLB overlap with AD in terms of clinical symptoms, cognitive test performance, and neuropathological features [109–113], it is relatively easy to detect dementia, but it remains challenging and critical to diagnose disease subtypes later [114].”
Aghdam, M. A., Bozdag, S., Saeed, F., & Initiative, A. D. N. (2025) · Brain Informatics · doi:10.1186/s40708-025-00252-3 · Cited by 52
“…related dementias (ADRD) is a growing public health crisis, affecting about 50 million people around the world, and 6 million people in the US (expected to rise to 14 million by 2050), leading to huge burden to patients, caretakers, and the healthcare sector ($250 Billion in the US alone) [1, 2].”
Vaccination strategies in tauopathies and synucleinopathies
Braczynski, A. K., Schulz, J. B., & Bach, J. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14207 · Cited by 44
Yoo, S.-H., Woo, S.-W., Shin, M., Yoon, J. A., Shin, Y., & Hong, K. (2021) · Current Alzheimer Research · doi:10.2174/1567205018666210212154941 · Cited by 43
Ma, Y., Bland, J. K. S., & Fujinami, T. (2024) · Diagnostics · doi:10.3390/diagnostics14192189 · Cited by 43
“The differential diagnosis of dementia subtypes, particularly the most prevalent forms, Alzheimer’s disease (AD) and frontotemporal dementia (FTD), is receiving increasing attention [1,2].”
BackgroundHaj, E., Losev, Y., KrishnaKumar, V. G., Pichinuk, E., Engel, H., Raveh, A., Gazit, E., & Segal, D. (2018) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2018.04.001 · Cited by 41
Wang, S., Liu, H., Cheng, Y.-C., & Su, C.-H. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph182413331 · Cited by 47
“It is a neurodegenerative disease in which nerve cells in the brain are damaged [5].”
BackgroundDiagnosing the frontal variant of Alzheimer’s disease: a clinician’s yellow brick road
Sawyer, R. P., Rodriguez-Porcel, F., Hagen, M., Shatz, R., & Espay, A. J. (2017) · Journal of Clinical Movement Disorders · doi:10.1186/s40734-017-0052-4 · Cited by 40
“While bvFTD patients may have mild difficulty with free recall early in the disease, recognition memory is typically intact and thus patients are able to recognize items with cueing, consistent with a retrievalpredominant deficit [24].”
BackgroundRigby, T., Johnson, D. K., Taylor, A., & Galvin, J. E. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201326 · Cited by 40
“The clinical features of AD, DLB, and PDD have both unique and overlapping aspects, with more overlap between disorders in the latter stages of disease [7].”
Self-citationKokkinou, M., Beishon, L., Smailagic, N., Noel-Storr, A. H., Hyde, C., Ukoumunne, O. C., Worrall, R., Hayen, A., Desai, M., Ashok, A. H., et al. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010945.pub2 · Cited by 43
Lok, K., Hong, Z., Zhang, C. M., He, N., Shen, H., Wang, Z., Zhao, W., & Yin, M. (2013) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2013.09.018 · Cited by 40
“Elevated open arm exploration is a sign of behavioral disinhibition, as seen in those AD patients with inappropriate hilarity and fugal states [25].”
BackgroundThe Role of IL-17A in Mediating Inflammatory Responses and Progression of Neurodegenerative Diseases
Zheng, M., & Luo, L. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26062505 · Cited by 43
“AD is the most common neurodegenerative disease causing cognitive impairment in the elderly [92,93].”
Kim, J. S., Han, J. W., Bae, J. B., Moon, D. G., Shin, J. Y., Kong, J. E., Lee, H., Yang, H. W., Lim, E., Kim, J. Y., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-22917-3 · Cited by 40
Olivari, B. S., Baumgart, M., Taylor, C. A., & McGuire, L. C. (2021) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12142 · Cited by 38
β‐Amyloid pathogenesis: Chemical properties versus cellular levels
Tiwari, M. K., & Kepp, K. P. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.06.1895 · Cited by 37
“It manifests in adult age as a gradual decline of cognitive, behavioral, and physical capabilities, and of identity, mood, and activity, ultimately leading to death [3,4].”
BackgroundNutrition: Review on the Possible Treatment for Alzheimer’s Disease
Botchway, B. O. A., Moore, M. K., Akinleye, F. O., Iyer, I. C., & Fang, M. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170874 · Cited by 38
“In some quarters, curcumin, vitamins, and Mediterranean diet have been postulated to possibly have a preventative role in AD [1, 7–9].”
Budgett, R. F., Bakker, G., Sergeev, E., Bennett, K. A., & Bradley, S. J. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.893422 · Cited by 38
“These diseases give rise to behavioral changes and cognitive decline (Karantzoulis and Galvin, 2011).”
BackgroundCousins, K. A. Q., Phillips, J. S., Irwin, D. J., Lee, E. B., Wolk, D. A., Shaw, L. M. J., Zetterberg, H., Blennow, K., Burke, S., Kinney, N. G., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12233 · Cited by 38
Yang, E.-J., Kim, H.-J., Choi, Y., Kim, H. J., Kim, J. H., Yoon, J., Seo, Y.-S., & Kim, H.-S. (2021) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2021.06.012 · Cited by 36
Neurocognitive Changes in Spinocerebellar Ataxia Type 3: A Systematic Review with a Narrative Design
Yap, K. H., Kessels, R. P. C., Azmin, S., van de Warrenburg, B. P. C., & Ibrahim, N. M. (2021) · The Cerebellum · doi:10.1007/s12311-021-01282-3 · Cited by 36
“Owing to the ruminative component of depression [83], depressive symptoms may exacerbate attention and EF impairment [83, 84].”
BackgroundMachine learning for the life-time risk prediction of Alzheimer’s disease: a systematic review
Rowe, T. W., Katzourou, I. K., Stevenson‐Hoare, J. O., Bracher‐Smith, M., Ivanov, D. K., & Escott‐Price, V. (2021) · Brain Communications · doi:10.1093/braincomms/fcab246 · Cited by 36
“Diagnosing the correct form of dementia has long proven difficult due to different forms sharing phenotypic characteristics.(4) Currently, the only method to confirm a diagnosis of a specific type of dementia, is post-mortem brain biopsy.”
John, S. E., Gurnani, A. S., Bussell, C. A., Saurman, J. L., Griffin, J. W., & Gavett, B. E. (2016) · Neuropsychology · doi:10.1037/neu0000315 · Cited by 36
“%) than in any other neurodegenerative disease, and these continue to be a good indicator for clinical diagnosis (Karantzoulis & Galvin, 2011), in addition to measured declines and impairment in visuospatial processing and processing speed.”
BackgroundVitamin Supplementation as an Adjuvant Treatment for Alzheimer’s Disease
Bhatti, A. B. (2016) · JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH · doi:10.7860/jcdr/2016/20273.8261 · Cited by 36
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“Alzheimer’s disease (AD) is a global public health concern [6] in part because executive function deficits often occur in concert with progressive learning and memory deficits [7].”
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Palliative Care in Advanced Dementia
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“5%).(2,3) These types of dementia have different neuropathologies and variable”
Obstructive sleep apnea may increase the risk of Alzheimer's disease
Przybylska-Kuć, S., Zakrzewski, M., Dybała, A., Kiciński, P., Dzida, G., Myśliński, W., Prystupa, A., Mosiewicz-Madejska, B., & Mosiewicz, J. (2019) · PLoS ONE · doi:10.1371/journal.pone.0221255 · Cited by 29
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Fania, C., Arosio, B., Capitanio, D., Torretta, E., Gussago, C., Ferri, E., Mari, D., & Gelfi, C. (2017) · PLoS ONE · doi:10.1371/journal.pone.0179280 · Cited by 25
Neural Substrates of Semantic Prospection – Evidence from the Dementias
Irish, M., Eyre, N., Dermody, N., O’Callaghan, C., Hodges, J. R., Hornberger, M., & Piguet, O. (2016) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2016.00096 · Cited by 33
“Keywords: episodic memory, semantic memory, imagination, hippocampus, prefrontal cortex, Alzheimer’s disease, frontotemporal dementia, future thinking Frontiers in Behavioral Neuroscience | www.frontiersin.org 1 May 2016 | Volume 10 | Article 96”
Background
Metadata
- Authors
- Karantzoulis, S., & Galvin, J. E.
- Affiliations
- NYU Langone Health (US)
- Corresponding author
- Karantzoulis, Stella
- 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
- 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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