Cognition and hippocampal volume in amyloid positive clinically normal adults: Results from the A4 study. (December 2021)

• Record Type: Journal Article
• Authors: Petersen, Kellen; Grober, Ellen; Lipton, Richard B.; Sperling, Reisa A.; Buckley, Rachel F.; Ezzati, Ali
• Is Part Of: Alzheimer's & dementia. Volume 17(2021)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.053102
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Recent studies suggests that sex and genomic differences influence the earliest neuropsychological and pathologic manifestations of Alzheimer's disease (AD). The relationship between individual cognitive status and the degree of neurodegeneration, and the influence of sex and APOE4 status on these relationships, remains uncertain. Using cross‐sectional data, we investigate the association between cognition in preclinical AD and adjusted hippocampal volume (HVa), a proxy for neurodegeneration related to memory. Method: Participants included 1169 cognitively unimpaired individuals aged 65 to 85 screened in the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's (A4) Study, who were amyloid positive, completed neuropsychological evaluations, and had APOE4 genotyping and structural MRIs. HVa was obtained by residual correction to account for sex differences in hippocampal and intracranial volumes. Association between HVa and cognition was evaluated using a two‐sample t‐test for the whole sample and subsamples stratified by sex and APOE4 status. Result: In the whole sample, lower HVa was linked with worse performance on measures of memory (Free Recall (FR): p=0.030; Total Recall 96 (TR96): p= 0.032), mental status (Mini‐Mental State Examination (MMSE): p= 0.048), executive functioning (Digit Symbol Substitution (DSS): p<0.001), and the Preclinical Alzheimer's Cognitive Composite (PACC: p<0.001) (Figure 1, Table 1). Based on comparison of effect sizes between groups, DSS and PACC were the most impacted measures to early neurodegeneration‐related cognitive decline while PACC and TR96 were the most impacted tests to advanced neurodegeneration‐related cognitive decline (Table 1). In multiple regression, adjusting for age and education, all cognitive measures except MMSE were associated with HVa among women (FR: p=0.012; TR96: p=0.007; Delayed Logical Memory (DLM): p=0.014; DSS: p<0.001; PACC: p<0.001), but not men. Among APOE4 positive individuals, all cognitive measures except MMSE were associated with HVa (FR: p=0.016; TR96: p=0.006; DLM: p=0.009; DSS: p=0.002; PACC: p<0.001), however, there was no association between cognition and HVa in APOE4 negative individuals. Conclusion: While all cognitive measures were significantly associated with neurodegeneration in amyloid positive individuals, cognitive tests show different sensitivities in detecting early or late signs of neurodegeneration as measured by HVa. There are clear differences in association between cognition and neurodegeneration based on sex and APOE4 status.