Abstract
Objective To identify the pathophysiologic mechanisms and clinical significance of anosognosia for cognitive decline in mild cognitive impairment.
Methods We stratified 468 patients with amnestic mild cognitive impairment into intact and impaired awareness groups, determined by the discrepancy between the patient and the informant score on the Everyday Cognition questionnaire. Voxel-based linear regression models evaluated the associations between self-awareness status and baseline β-amyloid load, measured by [18F]florbetapir, and the relationships between awareness status and regional brain glucose metabolism measured by [18F]fluorodeoxyglucose at baseline and at 24-month follow-up. Multivariate logistic regression tested the association of awareness status with conversion from amnestic mild cognitive impairment to dementia.
Results We found that participants with impaired awareness had lower [18F]fluorodeoxyglucose uptake and increased [18F]florbetapir uptake in the posterior cingulate cortex at baseline. In addition, impaired awareness in mild cognitive impairment predicted [18F]fluorodeoxyglucose hypometabolism in the posterior cingulate cortex, left basal forebrain, bilateral medial temporal lobes, and right lateral temporal lobe over 24 months. Furthermore, participants with impaired awareness had a nearly 3-fold increase in likelihood of conversion to dementia within a 2-year time frame.
Conclusions Our results suggest that anosognosia is linked to Alzheimer disease pathophysiology in vulnerable structures, and predicts subsequent hypometabolism in the default mode network, accompanied by an increased risk of progression to dementia. This highlights the importance of assessing awareness of cognitive decline in the clinical evaluation and management of individuals with amnestic mild cognitive impairment.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADAS-Cog=
- Alzheimer's Disease Assessment Scale–cognitive subscale;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- ANCOVA=
- analysis of covariance;
- CI=
- confidence interval;
- DMN=
- default mode network;
- ECog=
- everyday cognition;
- MCI=
- mild cognitive impairment;
- MMSE=
- Mini-Mental State Examination;
- OR=
- odds ratio;
- p-tau=
- phosphorylated tau;
- PCC=
- posterior cingulate cortex;
- RAVLT-D=
- Rey Auditory Verbal Learning Task–delayed recall;
- RAVLT-IM=
- Rey Auditory Verbal Learning Task–immediate recall memory;
- SUVR=
- standardized uptake value ratio;
- TMT-A=
- Trail-Making Test part A;
- TMT-B=
- Trail-Making Test part B
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Coinvestigators are listed at links.lww.com/WNL/A236.
Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.
The Article Processing Charge was funded by the authors.
- Received August 7, 2017.
- Accepted in final form December 5, 2017.
- Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
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