Self-reported memory complaints: implications from a longitudinal cohort with autopsies

Abstract

Objective: We assessed salience of subjective memory complaints (SMCs) by older individuals as a predictor of subsequent cognitive impairment while accounting for risk factors and eventual neuropathologies.

Methods: Subjects (n = 531) enrolled while cognitively intact at the University of Kentucky were asked annually if they perceived changes in memory since their last visit. A multistate model estimated when transition to impairment occurred while adjusting for intervening death. Risk factors affecting the timing and probability of an impairment were identified. The association between SMCs and Alzheimer-type neuropathology was assessed from autopsies (n = 243).

Results: SMCs were reported by more than half (55.7%) of the cohort, and were associated with increased risk of impairment (unadjusted odds ratio = 2.8, p < 0.0001). Mild cognitive impairment (dementia) occurred 9.2 (12.1) years after SMC. Multistate modeling showed that SMC reporters with an APOE ε4 allele had double the odds of impairment (adjusted odds ratio = 2.2, p = 0.036). SMC smokers took less time to transition to mild cognitive impairment, while SMC hormone-replaced women took longer to transition directly to dementia. Among participants (n = 176) who died without a diagnosed clinical impairment, SMCs were associated with elevated neuritic amyloid plaques in the neocortex and medial temporal lobe.

Conclusion: SMC reporters are at a higher risk of future cognitive impairment and have higher levels of Alzheimer-type brain pathology even when impairment does not occur. As potential harbingers of future cognitive decline, physicians should query and monitor SMCs from their older patients.

Figure 1. Flow diagram and frequency of transitions among states

Figure 2. Boxplots of neuritic plaque counts and neurofibrillary tangle counts in 2 brain regions

The boxplots provide neuritic plaque (NP) (A) and neurofibrillary tangle (NFT) (B) counts for each of 4 groups (in order and shaded light to dark): subjective memory complaint (SMC) negative and impaired negative; SMC positive and impaired negative; SMC negative and impaired positive; and SMC positive and impaired positive. *p < 0.05, ***p < 0.001.