Key Points Question How does lack of awareness (anosognosia) of memory impairment evolve in the Alzheimer disease (AD) trajectory? Findings In this cohort study of 2379 members of the Alzheimer’s Prevention Initiative Registry with a presenilin ( PSEN1 E280A) variant for autosomal dominant AD, awareness of memory function was increased in carriers and noncarriers approximately 14 years before their estimated median age of dementia onset (49 years). In variant carriers only, awareness of memory function was reduced in the predementia stages, reaching anosognosia 6 years before dementia onset. Meaning The findings suggest that alteration of awareness of memory function in predementia stages may inform practitioners about AD progression.

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Background: Most presume the diagnosis of MCI or early dementia to be a negative experience, yet we know from studies of other chronic health conditions that "even the darkest cloud may have a silver lining". The Silver Lining Questionnaire was developed and has been validated to assess the psychological impact of chronic health conditions on positive wellbeing in affected individuals. The present study was undertaken to examine this phenomena in those diagnosed with MCI or early dementia. Methods: Observational study of the University of Kentucky Alzheimer's Disease Center cohort subjects with MCI and early dementia (n¼48). Participants were administered the Silver Lining Questionnaire. Standard descriptive statistical methods were used to evaluate neuropsychiatric symptom change in this preliminary study. Results: Subjects were 78.968.6 years of age, 38% male, with 16.463.2 years of education, MMSE 26.062.8, CDR global score 0.560.1, and CDR sum of boxes 1.761.1. Forty seven percent of subjects surveyed reported positive scores on the Silver Lining Questionnaire. Greater than 50% positive response rates were seen for questions regarding 1) appreciation and acceptance of life, 2) less concerns about failure, 3) self-reflection, tolerance of others, and courage to face problems in life, 4) strengthened relationships and new opportunities to meet people. No differences were seen between subjects on basic demographic or clinical variables based on diagnosis or scores on the Silver Lining Questionnaire. Conclusions: These data demonstrate that positive changes in outlook on life are not only possible, but are as common as negative changes. Further studies of variables or interventions that could enhance life satisfaction in dementia could have a positive impact on the more than 50% of patients that cannot find their "silver lining" yet.

Background While loss of insight of cognitive deficits, anosognosia, is a common symptom in Alzheimer's disease (AD) dementia, there is a lack of consensus regarding the presence of altered awareness of memory function in the pre‐dementia stages of the disease. Here, we investigated the evolution of memory awareness in the AD‐course in a large cohort of individuals who carry mutations for autosomal dominant AD (ADAD; a population that are genetically determined to develop early‐onset dementia, and have a well‐characterized disease trajectory from pre‐symptomatic to clinical stages) and compared it with family members who do not carry the mutation. Methods Pseudo‐longitudinal analyses using linear mixed‐effect models was used to predict self‐awareness (assessed using an awareness index based on the discrepancy score between participant and study‐partner report on the Memory Complaint Scale (Spanish version),in a total of 2,379 members of a Colombian kindred including 396 ADAD (14.9% impaired) and 1,983 non‐carrier family members (Table 1). Age was entered as a fixed and random factor in the models. Results The mutation carriers complained significantly more than their study‐partner until the mean age of 35, and complained significantly less (unawareness/anosognosia) than their study‐partner around the age of 43 (Figure 1A), approximately 6 years prior to their estimated median age of dementia onset (49yo). Cognitively‐unimpaired non‐carriers complained significantly more than their study‐partners (heightened awareness/hypernosognosia) between ages 20‐60 (Figure 1B). Using the awareness index (Figure 2) we observed a decrease with age (est.=‐0.04 discrepant‐points/year,se=0.02,t=‐2.2,p=0.03) in the non‐carriers and an even steeper decline in the mutation carriers (est.=‐0.21 discrepant‐points/year,se=0.04,t=‐5.1,p=2.8*e‐7). The awareness index was significantly different between groups from age 22.5, indicating less awareness of memory in the mutation carriers as compared to the non‐carriers. Conclusion Hypernosognosia was observed in both groups, indicating that heightened awareness of memory function is common and non‐specific in this cohort. In mutation‐carriers, awareness of memory decreased in the pre‐dementia stages, reaching anosognosia 6 years before dementia onset. These findings provide further support for the usefulness of informant‐reported cognitive decline and add to the sporadic AD literature suggesting that individuals who become unaware of cognitive change in preclinical stages may represent a specific risk group to develop AD dementia.