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. 2022 Dec;9(12):1962-1973.
doi: 10.1002/acn3.51689. Epub 2022 Nov 17.

Early-onset Alzheimer's disease shows a distinct neuropsychological profile and more aggressive trajectories of cognitive decline than late-onset

Adrià Tort-Merino #  1 , Neus Falgàs #  1   2   3 , Isabel E Allen  3   4 , Mircea Balasa  1   3 , Jaume Olives  1 , José Contador  1 , Magdalena Castellví  1 , Jordi Juncà-Parella  1 , Núria Guillén  1 , Sergi Borrego-Écija  1 , Bea Bosch  1 , Guadalupe Fernández-Villullas  1 , Oscar Ramos-Campoy  1 , Anna Antonell  1 , Lorena Rami  1 , Raquel Sánchez-Valle  1   5 , Albert Lladó  1   5
Affiliations

Early-onset Alzheimer's disease shows a distinct neuropsychological profile and more aggressive trajectories of cognitive decline than late-onset

Adrià Tort-Merino et al. Ann Clin Transl Neurol. 2022 Dec.

Abstract

Objectives: Early- and late-onset Alzheimer's disease (EOAD and LOAD) share the same neuropathological traits but show distinct cognitive features. We aimed to explore baseline and longitudinal outcomes of global and domain-specific cognitive function in a well characterized cohort of patients with a biomarker-based diagnosis.

Methods: In this retrospective cohort study, 195 participants were included and classified according to their age, clinical status, and CSF AD biomarker profile: 89 EOAD, 37 LOAD, 46 young healthy controls (age ≤ 65 years), and 23 old healthy controls (>65 years). All subjects underwent clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture.

Results: We found distinct neuropsychological profiles between EOAD and LOAD at the time of diagnosis. Both groups showed similar performances on memory and language domains, but the EOAD patients displayed worsened deficits in visual perception, praxis, and executive tasks (p < 0.05). Longitudinally, cognitive decline in EOAD was more pronounced than LOAD in the global outcomes at the expense of these non-amnestic domains. We found that years of education significantly influenced the decline in most of the neuropsychological tests. Besides, the APOE ε4 status showed a significant effect on the decline of memory-related tasks within the EOAD cohort (p < 0.05).

Interpretation: Age of onset is a main factor shaping the cognitive trajectories in AD patients, with younger age driving to a steeper decline of the non-memory domains. Years of education are related to a transversal decline in all cognitive domains and APOE ε4 status to a specific decline in memory performance in EOAD.

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Conflict of interest statement

The authors do not have any competing financial or non‐financial interests related to the manuscript.

Figures

Figure 1
Figure 1
Baseline neuropsychological scores across the study groups. MMSE, Mini‐Mental State Examination; FCSRT, Free and Cued Selective Reminding Test; BDAE, Boston Diagnostic Aphasia Examination; WAB, Western Aphasia Battery; CERAD, Consortium to Establish a Registry for Alzheimer's Disease; VOSP, Visual Object and Space Perception Battery. Error bars represent SEM. TMTA z‐scores were inverted (sign change) for visualization purposes.
Figure 2
Figure 2
Neuropsychological progression of the study groups. MMSE, Mini‐Mental State Examination; FCSRT, Free and Cued Selective Reminding Test; BDAE, Boston Diagnostic Aphasia Examination; WAB, Western Aphasia Battery; CERAD, Consortium to Establish a Registry for Alzheimer's Disease; VOSP, Visual Object and Space Perception Battery. Error bars represent SEM. TMTA z‐scores were inverted (sign change) for visualization purposes.
Figure 3
Figure 3
Effect of the APOE genotype in memory decline. FCSRT, Free and Cued Selective Reminding Test.
See this image and copyright information in PMC

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References

    1. Garre‐Olmo J, Genis Batlle D, del Mar Fernandez M, et al. Incidence and subtypes of early‐onset dementia in a geographically defined general population. Neurology. 2010;75:1249‐1255. - PubMed
    1. Harvey R, Skelton‐Robinson M, Rossor M. The prevalence and causes of dementia in people under the age of 65 years. J Neurol Neurosurg Psychiatry. 2003;74:1206‐1209. - PMC - PubMed
    1. Lobo A, Launer LJ, Fratiglioni L, et al. Prevalence of dementia and major subtypes in Europe: a collaborative study of population‐based cohorts. Neurology. 2000;54:S4‐S9. - PubMed
    1. Apostolova LG, Aisen P, Eloyan A, et al. The longitudinal early‐onset Alzheimer's disease study (LEADS): framework and methodology. Alzheimers Dement. 2021;17(12):2043‐2055. - PMC - PubMed
    1. Graff‐Radford J, Yong KXX, Apostolova LG, et al. New insights into atypical Alzheimer's disease in the era of biomarkers. Lancet Neurol. 2021;20(3):222‐234. - PMC - PubMed