Degree of cognitive impairment does not signify early versus late mild cognitive impairment: confirmation based on Alzheimer's disease polygenic risk

NEUROBIOLOGY OF AGING

卷:94

Article

Elman, Jeremy A.^1,2  Vuoksimaa, Eero³  Franz, Carol E.^1,2  Kremen, William S.^1,2,4 

[1] Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,MC 0738, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Ctr Behav Genet Aging, La Jolla, CA 92093 USA

[3] Univ Helsinki, Inst Mol Med Finland FIMM, HiLIFE, Helsinki, Finland

[4] VA San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, La Jolla, CA USA

关键词: Alzheimer's disease (AD);    Mild cognitive impairment (MCI);    Polygenic risk scores (PRS);    Diagnostic criteria;   

DOI  :  10.1016/j.neurobiolaging.2020.05.015

来源: Elsevier

【 摘 要 】

Degree of memory impairment is often used to infer early versus late amnestic mild cognitive impairment (aMCI). Previously, 318 Alzheimer's Disease Neuroimaging Initiative participants with aMCIddetermined by a single memory testdwere divided based on Rey Auditory Verbal Learning Task (AVLT) delayed recall: AVLT-impaired (n = 225) and AVLT-normal (n = 93). Equally consistent with differential progression or differential diagnosis, the AVLT-impaired group had more abnormal Alzheimer's disease (AD) biomarkers, more neurodegeneration over time, and was more likely to develop AD. In the present study, higher AD polygenic risk scores were associated with increased odds of being AVLT-impaired (odds ratio 1.8, p < 0.001). Thus, impairment severity does not necessarily reflect early versus late aMCI because disease progression cannot alter polygenic risk. Presumed early MCI is likely a heterogeneous category that includes excess false-positives. The additional cognitive test improved diagnostic precision by reducing false positives. Impairment severity may reflect differences in underlying disease risk but cannot be used to infer early versus late MCI based on cross-sectional data alone. (C) 2020 Elsevier Inc. All rights reserved.

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