Editors' ChoiceNeurodegenerative Disease

No longer aware of what cannot be remembered

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Science Translational Medicine  16 Sep 2015:
Vol. 7, Issue 305, pp. 305ec158
DOI: 10.1126/scitranslmed.aad3615

How does awareness of memory loss relate to dementia? Wilson and colleagues used three ongoing longitudinal natural history studies of older adults without dementia at enrollment to show that lack of awareness of memory loss precedes dementia, and this lack of awareness is reflected in classic dementia brain pathology in post-mortem tissue.

Data was derived from three studies (the national Religious Orders study and two Chicago-area studies), and included 2092 older adults followed for an average of 7.7 years. Outcomes were collected annually and included a self-assessment of memory and a battery of 19 standard cognitive memory tests. Lack of awareness was defined as the degree to which a person’s self-assessment of memory underestimated their true memory impairment, and was derived from residuals of a mixed model comparing annual observed memory performance to annual subjective memory rating. Both subjective memory ratings and objective memory performance declined over time, and the slopes of decline were correlated. At baseline, there was no systematic tendency for people to over or underestimate their level of memory impairment. The change in memory awareness was evaluated in two additional cohorts: 239 incident cases of dementia (average follow up of 7.5 years before dementia onset and 3.3 years after diagnosis), and 385 participants who died with subsequent post-mortem brain pathology available (mean age of death 89.1 years). A decline in awareness of objective memory impairment started on average 2.6 years prior to dementia diagnosis, even after adjusting for gender and education. This decreased awareness of memory decline was associated with post-mortem brain pathology— in particular, inclusions containing TDP-43 (transactive response DNA-binding protein 43), tau tangle density, and number of cerebral infarctions.

The authors conclude that lack of awareness of cognitive decline is part of the natural history of late-life dementia and is related to accumulation of characteristic dementia pathologies. The main limitations to the study are related to participant selection for the ongoing longitudinal cohorts.

R. S. Wilson et al., Temporal course and pathologic basis of unawareness of memory loss in dementia. Neurology 10.1212/WNL.0000000000001935 (2015). [Abstract]

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