Early-Versus Late-Onset Alzheimer's Disease: More than Age Alone
Abstract
Alzheimer's disease (AD) is the most common cause of dementia at older age. Although less prevalent before the age of 65 years, it is still the most frequent cause of early-onset dementia followed by frontotemporal dementia. The typical presentation of AD is memory dysfunction, however, presentations with prominent cognitive impairment in other domains besides memory, like prominent apraxia, language problems, or executive dysfunction, may occur and are relatively more common in early-onset AD. In this retrospective descriptive study, we determined the prevalence of non-memory presentations in a large sample of early-onset AD patients compared to late-onset AD. The clinical files of 270 patients with AD starting before the age of 65 years and 90 patients with late-onset AD ( 65 years) were reviewed to assess clinical characteristics. Patients were classified as memory presentation and non-memory presentation according to their clinical presentation. The mean age of the early-onset group was 56 +/- 5 years and 74 +/- 6 years for the late-onset group. A third of the early-onset AD group presented with non-memory symptoms compared to only 6% in the late-onset group (p < 0.001). Within the group with non-memory presentations, apraxia/visuospatial dysfunction was the most prevalent presenting symptom (12%). Patients with early-onset AD often present with a non-memory phenotype, of which apraxia/visuospatial dysfunction is the most common presenting symptom. Atypical presentations of AD should be considered in the clinical differential diagnosis of early-onset dementia.
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Early-onset Alzheimer's disease is marked mainly by severe praxis, executive, and language impairment rather than memory loss.
“Regarding Alzheimer's disease, the most common variety found at a younger age (followed by frontotemporal dementia), earlyonset forms are characterized at the neuropsychological level primarily by severe praxis and executive and language impairment rather than memory loss.11”
From The Unique Experience of Spouses in Early-Onset Dementia (2013) · cites this paper as [11]
Cites
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 · see citing works
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
Studies of interference in serial verbal reactions
Stroop, J. R. (1935) · Journal of Experimental Psychology · doi:10.1037/h0054651 · Cited by 18,622 · see citing works
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
VALIDITY OF THE TRAIL MAKING TEST AS AN INDICATOR OF ORGANIC BRAIN DAMAGE
Reitan, R. M. (1958) · Perceptual and Motor Skills · doi:10.2466/pms.1958.8.3.271 · Cited by 7,925 · see citing works
Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria
Neary, D., Snowden, J. S., Gustafson, L., Passant, U., Stuss, D., Black, S., Freedman, M., Kertesz, A., Robert, P. H., Albert, M., et al. (1998) · Neurology · doi:10.1212/wnl.51.6.1546 · Cited by 5,047 · see citing works
Román, G. C., Tatemichi, T. K., Erkinjuntti, T., Cummings, J. L., Masdeu, J. C., Garcia, J. H., Amaducci, L., Orgogozo, J.-M., Brun, A., Hofman, A., et al. (1993) · Neurology · doi:10.1212/wnl.43.2.250 · Cited by 4,921 · see citing works
Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria
Dubois, B., Feldman, H. H., Jacova, C., DeKosky, S. T., Barberger-Gateau, P., Cummings, J., Delacourte, A., Galasko, D., Gauthier, S., Jicha, G., et al. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70178-3 · Cited by 4,411 · see citing works
Self-citationKaplan, E., Goodglass, H., Weıntraub, S., & Segal, O. (2001) · Medical Entomology and Zoology · Cited by 4,378 · see citing works
McKeith, I. G., Galasko, D., Kosaka, K., Perry, E. K., Dickson, D. W., Hansen, L. A., Salmon, D. P., Lowe, J., Mirra, S. S., Byrne, E. J., et al. (1996) · Neurology · doi:10.1212/wnl.47.5.1113 · Cited by 3,960 · see citing works
Le test de copie d'une figure complexe
Osterrieth, P. M. (1944) · Medical Entomology and Zoology · Cited by 1,617 · see citing works
An english translation of alzheimer’s 1907 paper, “über eine eigenartige erkankung der hirnrinde”
Stelzmann, R. A., Norman Schnitzlein, H., & Reed Murtagh, F. (1995) · Clinical Anatomy · doi:10.1002/ca.980080612 · Cited by 1,455 · see citing works
Mesulam, M. ‐. (2001) · Annals of Neurology · doi:10.1002/ana.91 · Cited by 1,001 · see citing works
Benson, D. F., Davis, R. J., & Snyder, B. D. (1988) · Archives of Neurology · doi:10.1001/archneur.1988.00520310107024 · Cited by 754 · see citing works
The logopenic/phonological variant of primary progressive aphasia
Gorno‐Tempini, M., Brambati, S. M., Ginex, V., Ogar, J., Dronkers, N. F., Marcone, A., Perani, D., Garibotto, V., Cappa, S. F., & Miller, B. L. (2008) · Neurology · doi:10.1212/01.wnl.0000320506.79811.da · Cited by 700 · see citing works
Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech
Josephs, K. A. (2006) · Brain · doi:10.1093/brain/awl078 · Cited by 679 · see citing works
The prevalence and causes of dementia in people under the age of 65 years
Harvey, R. J. (2003) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.74.9.1206 · Cited by 650 · see citing works
Galton, C. J. (2000) · Brain · doi:10.1093/brain/123.3.484 · Cited by 613 · see citing works
Focal cortical presentations of Alzheimer's disease
Alladi, S., Xuereb, J., Bak, T., Nestor, P., Knibb, J., Patterson, K., & Hodges, J. R. (2007) · Brain · doi:10.1093/brain/awm213 · Cited by 581 · cited 1× · see citing works
“The pathology causing PPA is most often of the non-Alzheimer type, including frontotemporal lobar degen-1406 eration, although underlying AD pathology has also been reported [10,14,15,38,44].”
Clinical and Pathological Evidence for a Frontal Variant of Alzheimer Disease
Johnson, J. K., Head, E., Kim, R., Starr, A., & Cotman, C. W. (1999) · Archives of Neurology · doi:10.1001/archneur.56.10.1233 · Cited by 414 · see citing works
A Comparison of Clinical Features in Early- and Late-Onset Primary Degenerative Dementia
Seltzer, B. (1983) · Archives of Neurology · doi:10.1001/archneur.1983.04050030037006 · Cited by 365 · see citing works
Posterior Cortical Atrophy: Clinical Characteristics and Differences Compared to Alzheimer’s Disease
Mendez, M. F., Ghajarania, M., & Perryman, K. M. (2002) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000058331 · Cited by 364 · see citing works
Visual association test to detect early dementia of the Alzheimer type
Lindeboom, J. (2002) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.73.2.126 · Cited by 359 · see citing works
Clinical and pathological characterization of progressive aphasia
Knibb, J., Xuereb, J., Patterson, K., & Hodges, J. R. (2006) · Annals of Neurology · doi:10.1002/ana.20700 · Cited by 346 · see citing works
Hof, P. R., Vogt, B. A., Bouras, C., & Morrison, J. H. (1997) · Vision Research · doi:10.1016/s0042-6989(96)00240-4 · Cited by 246 · see citing works
Neuropathology of Alzheimer’s disease: a critical update
Jellinger, K. A., & Bancher, C. (1998) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-7508-8_8 · Cited by 231 · see citing works
Clinical subtypes of Alzheimer’s disease
Petersen, R. C. (1998) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000051199 · Cited by 223 · see citing works
Hodges, J. R. (2006) · Brain · doi:10.1093/brain/awl275 · Cited by 210 · see citing works
Word-finding difficulty: a clinical analysis of the progressive aphasias
Rohrer, J. D., Knight, W. D., Warren, J. D., Fox, N. C., Rossor, M. N., & Warren, J. D. (2007) · Brain · doi:10.1093/brain/awm251 · Cited by 190 · see citing works
The Accurate Diagnosis of Early-Onset Dementia
Mendez, M. F. (2006) · The International Journal of Psychiatry in Medicine · doi:10.2190/q6j4-r143-p630-kw41 · Cited by 181 · see citing works
Progressive biparietal atrophy: an atypical presentation of Alzheimer's disease.
Ross, S. J., Graham, N. L., Stuart-Green, L., Prins, M., Xuereb, J. H., Patterson, K. E., & Hodges, J. R. (1996) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.61.4.388 · Cited by 177 · see citing works
Progressive aphasia secondary to Alzheimer disease vs FTLD pathology
Josephs, K. A., Whitwell, J. L., Duffy, J. R., VanVoorst, W. A., Strand, E. A., Hu, W. T., Boeve, B. F., Graff‐Radford, N. R., Parisi, J. E., Knopman, D. S., et al. (2007) · Neurology · doi:10.1212/01.wnl.0000287073.12737.35 · Cited by 153 · see citing works
Neuropsychologic Features of Early- and Late-Onset Alzheimer's Disease
Filley, C. M., Kelly, J., & Heaton, R. K. (1986) · Archives of Neurology · doi:10.1001/archneur.1986.00520060038014 · Cited by 138 · see citing works
Variability in cognitive presentation of Alzheimer's disease
Stopford, C. L., Snowden, J. S., Thompson, J. C., & Neary, D. (2007) · Cortex · doi:10.1016/j.cortex.2005.11.002 · Cited by 133 · see citing works
The effect of APOE genotype on clinical phenotype in Alzheimer disease
van der Flier, W. M., Schoonenboom, S. N. M., Pijnenburg, Y. A. L., Fox, N. C., & Scheltens, P. (2006) · Neurology · doi:10.1212/01.wnl.0000228222.17111.2a · Cited by 98 · see citing works
Self-citationPresenile dementia syndromes: an update on taxonomy and diagnosis
Greicius, M. D. (2002) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.72.6.691 · Cited by 85 · see citing works
Neural substrates of cognitive and behavioral deficits in atypical Alzheimer's disease
von Gunten, A., Bouras, C., Kövari, E., Giannakopoulos, P., & Hof, P. R. (2006) · Brain Research Reviews · doi:10.1016/j.brainresrev.2005.11.003 · Cited by 75 · see citing works
Cognitive Differences between Early- and Late-Onset Alzheimer's Disease
Licht, E. A., McMurtray, A. M., Saul, R. E., & Mendez, M. F. (2007) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317506299156 · Cited by 68 · see citing works
Shinagawa, S., Ikeda, M., Toyota, Y., Matsumoto, T., Matsumoto, N., Mori, T., Ishikawa, T., Fukuhara, R., Komori, K., Hokoishi, K., et al. (2007) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000102596 · Cited by 66 · see citing works
Posterior Cortical Atrophy: A Review of the Literature
Caine, D. (2004) · Neurocase · doi:10.1080/13554790490892239 · Cited by 63 · see citing works
Suribhatla, S., Baillon, S. F., Dennis, M., Marudkar, M., Muhammad, S., Munro, D., Spreadbury, C., & Lindesay, J. E. B. (2004) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.1196 · Cited by 44 · see citing works
Cognitive Deficits in Familial Alzheimer’s Disease Associated with M239V Mutation of Presenilin 2
Gıovagnolı, A. R., Marcon, G., Giaccone, G., Confaloni, A., & Tagliavini, F. (2006) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000094972 · Cited by 11 · see citing works
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Graff-Radford, J., Yong, K. X. X., Apostolova, L. G., Bouwman, F. H., Carrillo, M., Dickerson, B. C., Rabinovici, G. D., Schott, J. M., Jones, D. T., & Murray, M. E. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30440-3 · Cited by 706 · see citing works
Babulal, G. M., Quiroz, Y. T., Albensi, B. C., Arenaza‐Urquijo, E., Astell, A. J., Babiloni, C., Bahar‐Fuchs, A., Bell, J., Bowman, G. L., Brickman, A. M., et al. (2019) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.09.009 · Cited by 528 · see citing works
Hamelin, L., Lagarde, J., Dorothée, G., Leroy, C., Labit, M., Comley, R. A., de Souza, L. C., Corne, H., Dauphinot, L., Bertoux, M., et al. (2016) · Brain · doi:10.1093/brain/aww017 · Cited by 519 · see citing works
Inconsistencies and Controversies Surrounding the Amyloid Hypothesis of Alzheimer's Disease
Morris, G. P., Clark, I. A., & Vissel, B. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0135-5 · Cited by 522 · see citing works
Clinical, imaging, and pathological heterogeneity of the Alzheimer's disease syndrome
Lam, B., Masellis, M., Freedman, M., Stuss, D. T., & Black, S. E. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt155 · Cited by 386 · see citing works
Lehmann, M., Ghosh, P. M., Madison, C., Laforce, R., Corbetta-Rastelli, C., Weiner, M. W., Greicius, M. D., Seeley, W. W., Gorno-Tempini, M. L., Rosen, H. J., et al. (2013) · Brain · doi:10.1093/brain/aws327 · Cited by 325 · see citing works
Functional cognitive disorder: dementia’s blind spot
Ball, H. A., McWhirter, L., Ballard, C., Bhome, R., Blackburn, D. J., Edwards, M. J., Fleming, S. M., Fox, N. C., Howard, R., Huntley, J., et al. (2020) · Brain · doi:10.1093/brain/awaa224 · Cited by 203 · see citing works
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Smits, L. L., Pijnenburg, Y. A. L., Koedam, E. L. G. E., van der Vlies, A. E., Reuling, I. E. W., Koene, T., Teunissen, C. E., Scheltens, P., & van der Flier, W. M. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-111934 · Cited by 182 · see citing works
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Slattery, C. F., Beck, J. A., Harper, L., Adamson, G., Abdi, Z., Uphill, J., Campbell, T., Druyeh, R., Mahoney, C. J., Rohrer, J. D., et al. (2014) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.05.1751 · Cited by 119 · see citing works
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Falgàs, N., Sánchez-Valle, R., Bargalló, N., Balasa, M., Fernández-Villullas, G., Bosch, B., Olives, J., Tort-Merino, A., Antonell, A., Muñoz-García, C., et al. (2019) · NeuroImage: Clinical · doi:10.1016/j.nicl.2019.101927 · Cited by 47 · see citing works
Falgàs, N., Ruiz‐Peris, M., Pérez‐Millan, A., Sala‐Llonch, R., Antonell, A., Balasa, M., Borrego‐Écija, S., Ramos‐Campoy, O., Augé, J. M., Castellví, M., et al. (2020) · Human Brain Mapping · doi:10.1002/hbm.24925 · Cited by 32 · see citing works
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“atrophy patterns depend mostly on the age of onset of AD [27], the AD group was separated into Early-onset”
Functional cognitive disorders: identification and management
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- Authors
- Koedam, E. L. G. E., Lauffer, V., van der Vlies, A. E., van der Flier, W. M., Scheltens, P., & Pijnenburg, Y. A. L.
- Affiliations
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- GGZ inGeest (NL)
- Alzheimer Centre and Department of Neurology, VU University Medical Centre, Amsterdam, The Netherlands
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2010-03-11
- Volume
- 19
- Issue
- 4
- Pages
- 1401-1408
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1486380975
- Cited by
- 452
- References
- 42
- Citations by year
- 2026: 20 · 2025: 26 · 2024: 38 · 2023: 29 · 2022: 35 · 2021: 44 · 2020: 37 · 2019: 29 · 2018: 17 · 2017: 32 · 2016: 23 · 2015: 34 · 2014: 21 · 2013: 30 · 2012: 22
- FWCI
- 14.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Vanderbilt University Medical Center
- Stichting Dioraphte
- Alzheimer Nederland
- FONDATION ALZHEIMER
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Social Sciences › Psychology › Clinical Psychology › Historical and Modern Theater Studies
- Keywords
- early-onset Alzheimer's disease, late-onset Alzheimer's disease
- MeSH terms
- Age Factors, Aged, Alzheimer Disease, Brain, Female, Humans, Male, Memory Disorders, Middle Aged, Neuropsychological Tests, Severity of Illness Index, Age of Onset
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