Subtle cognitive difficulties increase risk of neurodegeneration, incident mild cognitive impairment, and dementia in older women.

Abstract

AbstractBackgroundIdentifying individuals with preclinical Alzheimer’s disease and related disorders (ADRD) is important for prevention and eventual treatment. Here we aimed to integrate overall test performance with episodic memory process scores in a cohort of older women to identify those with subtle cognitive difficulties (SCD; e.g., individuals with the earliest declines in cognitive ability preceding a diagnosis of mild cognitive impairment (MCI) or dementia) and determine subsequent risk of MCI, dementia, and neuroimaging indices of neurodegeneration.MethodParticipants included 2,186 community‐dwelling older women without MCI or dementia (Mage = 73.4±3.8 years) who completed a comprehensive neuropsychological assessment as part of the Women’s Health Initiative Study of Cognitive Aging (WHISCA: 1999‐2000). Women were assessed annually for MCI and dementia until 2021, and 1,024 women underwent structural magnetic resonance imaging (sMRI) of the brain in 2005‐6. Women were classified as cognitively normal (CN), early SCD (e‐SCD; two episodic memory process scores 1 SD below normative means or one process score and one performance score 1 SD below normative means), or late SCD (l‐SCD; two overall performance scores 1 SD below normative means) at WHISCA baseline using validated criteria from the Alzheimer’s Disease Neuroimaging Cohort (Thomas et al., 2018 Journal of Alzheimer’s Disease). We used Cox proportional hazards to examine associations between SCD status and risk of developing MCI/dementia. Linear regressions were used to examine associations between SCD status and MRI indices of AD‐related neurodegeneration, global cerebrovascular damage, and brain volumes of structures that make up the medial temporal lobe. All associations were adjusted for sociodemographic, lifestyle, and clinical characteristics.ResultWomen with e‐SCD and l‐SCD were 1.58 (p<0.001) and 3.01 (p<0.001) times as likely to develop MCI/dementia compared to CN women, respectively (Figure 1). Women with l‐SCD (β = 0.20; p<0.001) had more AD‐related neurodegeneration compared to CN women (Table 1). Women with e‐SCD had marginally significantly greater AD‐related neurodegeneration (β = 0.14; p = 0.073) and had smaller volumes in the entorhinal cortex (β = ‐0.22; p = 0.009) compared to CN women.ConclusionOur study demonstrates the usefulness of the SCD criteria for the early identification of cognitively normal women who are at increased risk of MCI, dementia, and neurodegeneration.