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. 2020 Dec 1;3(12):e2027472.
doi: 10.1001/jamanetworkopen.2020.27472.

Trajectory of Unawareness of Memory Decline in Individuals With Autosomal Dominant Alzheimer Disease

Patrizia Vannini  1   2   3   4   5 , Bernard J Hanseeuw  1   4   5   6   7 , Jennifer R Gatchel  4   8   9 , Sietske A M Sikkes  10 , Diana Alzate  11 , Yesica Zuluaga  11 , Sonia Moreno  11 , Luis Mendez  11 , Ana Baena  8   11 , Paula Ospina-Lopera  11 , Victoria Tirado  11 , Eliana Henao  11   12 , Natalia Acosta-Baena  11 , Margarita Giraldo  11 , Francisco Lopera  11 , Yakeel T Quiroz  1   2   4   8   11
Affiliations

Trajectory of Unawareness of Memory Decline in Individuals With Autosomal Dominant Alzheimer Disease

Patrizia Vannini et al. JAMA Netw Open. .

Abstract

Importance: Recent studies have suggested that unawareness, or anosognosia, of memory decline is present in predementia stages of Alzheimer disease (AD) and may serve as an early symptomatic indicator of AD.

Objective: To investigate the evolution of anosognosia of memory decline in individuals who carry the PSEN1 E280A variant for autosomal dominant AD compared with family members who do not carry the variant.

Design, setting, and participants: This cohort study investigated a total of 2379 members of a Colombian kindred with autosomal dominant AD who were part of the Alzheimer's Prevention Initiative Registry. Assessments were completed at the University of Antioquia, Colombia, with data collected between January 1, 2000, and July 31, 2019.

Main outcomes and measures: Awareness of memory function was operationalized using the discrepancy between self-report and study partner report on a memory complaint scale. Linear mixed effects models were used to assess memory self-awareness over age separately in variant carriers and noncarriers.

Results: This study included 396 variant carriers (mean [SD] age, 32.7 [11.9] years; 200 [50.5%] female), of whom 59 (14.9%) were cognitively impaired, and 1983 cognitively unimpaired noncarriers (mean [SD] age, 33.5 [12.5] years; 1129 [56.9%] female). The variant carriers demonstrated increased awareness until the mean (SD) age of 35.0 (2.0) years and had anosognosia at approximately 43 years of age, approximately 6 years before their estimated median age of dementia onset (49 years; 95% CI, 49-51 years). Cognitively unimpaired noncarriers reported more complaints than their study partners aged 20 and 60 years (10.1 points, P < .001). On the awareness index, a decrease with age (mean [SE] estimate, -0.04 [0.02] discrepant-points per years; t = -2.2; P = .03) in the noncarriers and in the variant carriers (mean [SE] estimate, -0.21 [0.04] discrepant-points per years; t = -5.1; P < .001) was observed.

Conclusions and relevance: 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. 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Vannini reported receiving grants from the National Institute on Aging (NIA), National Institutes of Health (NIH) during the conduct of the study. Dr Hanseeuw reported receiving grants from the Belgian National Fund for Scientific Research during the conduct of the study. Dr Gatchel reported receiving grant support from the NIA, NIH and the Alzheimer's Association (Alzheimer's Association Clinical Fellowship), receiving research support from Merck, and serving as a 1-time consultant for Huron Consulting. Dr Sikkes reported receiving grants from Zon-MW during the conduct of the study and license fees from Amsterdam IADL outside the submitted work. Dr Lopera reported receiving grants from the NIH, Banner Foundation, and Roche during the conduct of the study. Dr Quiroz reported receiving grants from the NIA, NIH, the Massachusetts General Hospital Executive Committee on Research, and the Alzheimer's Association during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Episodic Memory in Variant Carriers and Noncarriers
Shading represents 95% CIs.
Figure 2.
Figure 2.. Awareness in Variant Carriers and Noncarriers
Negative scores indicate an overestimation of memory functioning or low awareness of memory function, indicating that these individuals believed they were functioning at a higher level than their partners rated. In contrast, a positive awareness index score indicates underestimation of memory functioning or increased awareness of memory function, indicating that these individuals believed they were functioning worse than their partners rated. An awareness score of 0 indicates that the participant and the study partner judged memory similarly, suggesting that the participant had insight into their memory functioning. Shading represents 95% CIs.
Figure 3.
Figure 3.. Participant and Partner Complaints Among Variant Carriers and Noncarriers
The mean estimated age of dementia onset is 49 years. Shading represents 95% CIs.
See this image and copyright information in PMC

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