lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

Autopsy Findings of Cerebral β-Amyloidosis, Tauopathy, and Neurodegeneration (A,T, and (N)) in a Community-Based Sample: Implications for Dementia Mitigation Strategies

54 Pages Posted: 20 Feb 2019

See all articles by Bridget Burke

Bridget Burke

Kaiser Permanente Washington Health Research Institute

Caitlin Latimer

affiliation not provided to SSRN

C. Dirk Keene

University of Washington - Department of Pathology

Thomas J. Montine

affiliation not provided to SSRN

Joshua A. Sonnen

affiliation not provided to SSRN

Wayne McCormick

affiliation not provided to SSRN

James D. Bowen

affiliation not provided to SSRN

Susan M. McCurry

affiliation not provided to SSRN

Eric B. Larson

affiliation not provided to SSRN

Paul K. Crane

affiliation not provided to SSRN

More...

Abstract

Background: A recent Alzheimer's disease research diagnosis framework groups amyloid (A), tauopathy (T), and neurodegeneration (N) biomarkers into eight AT(N) profiles. We determined prevalence at death of each profile in the Adult Changes in Thought (ACT) community-based cohort. Within each profile, we determined dementia prevalence at death and incident dementia among those dementia free 5-7 years antemortem.

Methods: Setting: prospective study of individuals ≥65 years; 25-30% consented to autopsy. Cognition was prospectively evaluated every 2 years and dementia determined using research criteria. At autopsy, A used CERAD levels (none/sparse vs. moderate/frequent), T used Braak staging (0-III vs. IV-VI), and N used absence vs. presence of lateral ventricular dilation at the temporal tip. We compared prevalent and incident dementia for each AT(N) profile. We used inverse-probability weighting to address potential selection bias, and considered the relevance of seven additional autopsy findings in predicting dementia status.

Findings: Of 5,236 ACT participants, 2,870 died, and 603 had known dementia status and autopsy. The two most common profiles were A+T+(N)+ (31%) and A-T-(N)+ (22%). Dementia prevalence ranged from 14% (A-T-(N)-) to 79% (A+T+(N)+). Dementia incidence ranged from 8% (A+T-(N)-) to 67% (A+T+(N)+) and 68% (A+T+(N)-). Each additional neuropathological finding was associated with 7% (prevalence) to 9% (incidence) higher dementia risk independent of A,T and (N) (prevalence RR 1·07 (95% CI: 1·05-1·10); incidence RR 1·09 (95% CI: 1·05-1·14)).

Interpretation: Dementia rates varied across AT(N) categories. Costs of determining AT(N) status may be considerable. That >30% of dementia-free people with the highest risk AT(N) categories did not develop incident dementia before death suggests restraint in population-based settings for treatments with more than trivial toxicity.

Funding Statement: National Institute on Aging (US National Institutes of Health). (AG006781)

Declaration of Interests: PKC reports grants from the US National Institutes of Health (NIH) and prior funding from the Alzheimer’s Association.

Ethics Approval Statement: Study procedures were approved by KPW and UW institutional review boards. Participants provided written informed consent.

Suggested Citation

Burke, Bridget and Latimer, Caitlin and Keene, C. Dirk and Montine, Thomas J. and Sonnen, Joshua A. and McCormick, Wayne and Bowen, James D. and McCurry, Susan M. and Larson, Eric B. and Crane, Paul K., Autopsy Findings of Cerebral β-Amyloidosis, Tauopathy, and Neurodegeneration (A,T, and (N)) in a Community-Based Sample: Implications for Dementia Mitigation Strategies (April 2, 2019). Available at SSRN: https://ssrn.com/abstract=3335065 or http://dx.doi.org/10.2139/ssrn.3335065

Bridget Burke (Contact Author)

Kaiser Permanente Washington Health Research Institute ( email )

1730 Minor Ave
Seattle, WA 98195
United States

Caitlin Latimer

affiliation not provided to SSRN

C. Dirk Keene

University of Washington - Department of Pathology

Seattle, WA 98115
United States

Thomas J. Montine

affiliation not provided to SSRN

Joshua A. Sonnen

affiliation not provided to SSRN

Wayne McCormick

affiliation not provided to SSRN

James D. Bowen

affiliation not provided to SSRN

Susan M. McCurry

affiliation not provided to SSRN

Eric B. Larson

affiliation not provided to SSRN

Paul K. Crane

affiliation not provided to SSRN

Click here to go to TheLancet.com

Paper statistics

Abstract Views
119
Downloads
8