Awareness of memory decline decreases in predementia stages among AD variant carriers

Carriers of a variant for autosomal dominant Alzheimer’s disease and family members who did not carry the variant both experienced awareness of memory decline, but awareness of memory function decreased in carriers in predementia stages.

Researchers published their findings in JAMA Network Open.

“A consensus is lacking regarding the presence and evolution of altered awareness of memory function across the preclinical and prodromal stages of AD,” Patrizia Vannini, PhD, of the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Brigham and Women’s Hospital and Harvard Medical School, and colleagues wrote. “The present study aimed to characterize alterations in awareness of memory function in a large cohort of descendants of individuals from the Colombian kindred with a variant in presenilin (PSEN1 [OMIM 104311] E280A that causes early-onset dementia (estimated median age of dementia onset, 49 years; 95% CI, 49-51 years).”

Vannini and colleagues conducted a cohort study of 2,379 participants from the Alzheimer’s Prevention Initiative Registry. This included 396 carriers of the PSEN1 E28OA variant (mean age, 32.7 years; 50.5% female), 14.9% of whom were cognitively impaired, and 1,983 participants who were not carriers of the variant and who did not have cognitive impairment (mean age, 33.5 years; 56.9% female).

Researchers collected data from 2000 through 2019 and examined changes in anosognosia, or unawareness, of memory decline in participants with the PSEN1 E28OA variant compared with family members who did not carry the variant. The main outcome measure was awareness of memory function, which researchers defined as “the discrepancy between self-report and study partner report on a memory complaint scale.”

Variant carriers demonstrated greater awareness until a mean age of 35 years that progressed to anosognosia by a mean age of approximately 43 years. Estimated median age of dementia onset was 49 years for these participants (95% CI, 49-51 years). Variant carriers with cognitive impairment (n = 59) reported more memory complaints than carriers without cognitive impairment (n = 337) and noncarriers (n = 1,983).

Mean awareness index scores declined with participant age (mean estimate, -0.04 discrepant-points per year; P < .001).

“In this cohort study, increased participant complaints were observed in both groups, suggesting that increased awareness of memory function was common and nonspecific to AD in this cohort,” researchers wrote. “In variant carriers, awareness of memory function decreased in the predementia stages, reaching anosognosia close to the age of mild cognitive impairment onset, providing support for the usefulness of awareness of memory decline.”