Subjective memory complaints in preclinical autosomal dominant Alzheimer disease

Abstract

Objective: To cross-sectionally study subjective memory complaints (SMC) in autosomal dominant Alzheimer disease (ADAD).

Methods: We examined self-reported and study partner-based SMC in 52 young, cognitively unimpaired individuals from a Colombian kindred with early-onset ADAD. Twenty-six carried the PSEN-1 E280A mutation, averaging 7 years of age younger than the kindred's expected clinical onset. Twenty-six were age-matched noncarriers. Participants also underwent structural MRI and cognitive testing.

Results: Self-reported SMC were greater in carriers than noncarriers (p = 0.02). Study partner-based SMC did not differ between groups (p = 0.21), but in carriers increased with age (r = 0.66, p < 0.001) and decreased with hippocampal volume (r = -0.35, p = 0.08).

Conclusions: Cognitively unimpaired PSEN-1 carriers have elevated SMC. Self-reported SMC may be a relatively early indicator of preclinical AD, while partner- reported SMC increases later in preclinical AD, closer to clinical onset.

Figure 1. Subjective memory complaints (SMC) as a function of age in autosomal dominant Alzheimer disease

Regression lines are shown for the best fitting function out of the 3 that were tested: sigmoidal, linear, and quadratic. For carriers, study partner–based SMC were best fit by a sigmoidal function (r² = 0.45) (A), while self-reported SMC did not vary significantly as a function of age for any of the 3 models used (r² < 0.06) (B), and a linear model is shown. For noncarriers, none of the 3 functions fit the data significantly, and linear models are shown.

Figure 2. Subjective memory complaint changes relative to objective cognitive and brain structural changes

Age-associated curves for PSEN1 mutation carriers shown for subjective memory complaints (study partner–based memory complaints), Consortium to Establish a Registry for Alzheimer's Disease (CERAD) word delayed recall scores, and hippocampal volume. Ages at which carriers and noncarriers began to reliably differ are also shown on each metric.