Unawareness (anosognosia) of memory decline in individuals who carry the PSEN1 E280A variant for autosomal-dominant Alzheimer’s disease may serve as an indicator of cognitive impairment, according to a study published in JAMA Network Open

Because of the risk of a person putting themselves in dangerous situations, awareness of memory decline is important to ensure individuals with Alzheimer’s make “healthy and safe” everyday life decisions. For this study, the researchers wanted to assess the change in awareness of memory function in early stages of Alzheimer’s disease.

The cohort study used participants enrolled in the Columbia Alzheimer’s Prevention Initiative Registry. The study included 2,379 participants — 396 of them carried the presenilin (PSEN1 E280A) variant. Of those that carried the variant, 59 were cognitively impaired. The researchers used a memory complaint scale to measure self-awareness of memory performance.

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The awareness index significantly decreased with age (mean [SE] estimate, −0.04 [0.02] discrepant-points per years; t = −2.2; P = .03) in noncarriers of the variant. In the variant carriers, awareness index decreased compared with the noncarriers (mean [SE] estimate, −0.21 [0.04] discrepant points per years; t = −5.1; P < .001).

Variant carriers complained significantly more than non-variant carriers until the mean age of 35. They complained significantly less (anosognosia) than non-variant carriers at the mean age of 43. The estimated median age of dementia onset in these groups was 49 years. Cognitively unimpaired noncarriers complained significantly more than non-variant age 20 and 60. In other words, variant carriers reached anosognosia about 6 years before the estimated median dementia onset.

Limitations include that this was a pseudo-longitudinal study. Awareness was assessed by memory reports, with no assessment of language or executive function.

“New biobehavioral preventive research that focuses on identifying individuals in a preclinical state when independent functioning and decision-making are preserved and when strategies to bolster self-awareness may have the greatest impact appears to be needed,” the researchers concluded.


Vannini P, Hanseeuw BJ, Gatchel JR, et al. Trajectory of unawareness of memory decline in individuals with autosomal dominant Alzheimer disease. JAMA Netw Open. Published online December 2, 2020. doi:10.1001/jamanetworkopen.2020.27472