Association of Subjective Memory Complaints With Neuropathologic Changes at Age 90 or Older: The 90+ Study

Subjective memory complaints (SMCs), defined as perception of one's own memory problems, have been associated with Alzheimer disease (AD) neuropathologic changes. Yet, whether SMC is associated with non-AD neuropathologic changes and whether this association is present in both those with normal cognition and those with cognitive impairment is not known. We examined the association of SMC with neurodegenerative and vascular neuropathologic changes in individuals aged 90 and older (oldest old) without dementia at death.

We analyzed data from The 90+ Study, an ongoing longitudinal study of aging in Southern California. The study enrolled individuals older than 90 years with evaluations every 6 months and followed until death. Cross-sectional analyses included participants with an SMC evaluation, no dementia at death, and a neuropathologic examination. The predictor, SMC, was defined as a "yes" response to the question from the Geriatric Depression Questionnaire (GDS), "Do you feel you have more problems with memory than most?" at any time during the follow-up. The outcomes were 12 neuropathologic changes, both vascular and neurodegenerative, dichotomized as present/absent. We estimated odds ratio (OR) and 95% CI in the entire group and separately for individuals classified with normal cognition and Cognitive Impairment No Dementia (CIND) at a postmortem case conference using logistic regression adjusted for demographics, GDS minus the SMC item, and Mini-Mental State Examination.

In the 238 participants (mean age at autopsy = 97.5 years, 62% women), 51% had normal cognition at death and 28% reported SMC at some point during follow-up. In the entire group, individuals with SMC had higher odds of atherosclerosis (OR 2.07; 95% CI 1.12-2.83) compared with those without SMC. Among individuals with normal cognition, those with SMC had higher odds of AD neuropathologic change (OR 2.88; 95% CI 1.05-7.92), Lewy Body Disease (OR 3.56; 95% CI 1.07-11.83), and atherosclerosis (OR 3.13; 95% CI 1.21-8.09) compared with no SMC. In individuals with CIND, SMC were not associated with neuropathologic changes.

In the oldest old with normal cognition at death SMC were associated with neurodegenerative and vascular neuropathologic changes, suggesting that underlying pathology of SMC is multifactorial.