Amyloid PET predicts longitudinal functional and cognitive trajectories in a heterogeneous cohort

Author:

Younes Kyan1,Johns Emily1,Young Christina B.1,Kennedy Gabriel1,Mukherjee Shubhabrata2,Vossler Hillary A.1,Winer Joseph1,Cody Karly1,Henderson Victor W.13,Poston Kathleen L.1,Betthauser Tobey J.4,Bevis Bill4,Brooks William M.5,Burns Jeffrey M.5,Coombes Stephen A.6,DeCarli Charles7,DiFilippo Frank P.8,Duara Ranjan6,Fan Audrey P.7,Gibbons Laura E.2,Golde Todd6,Johnson Sterling C.4,Lepping Rebecca J.5,Leverenz James8,McDougall Sean7,Rogalski Emily9,Sanders Elizabeth2,Pasaye Joshua10,Sridhar Jaiashre10,Saykin Andrew J.11,Sridharan Anjali4,Swerdlow Russell5,Trittschuh Emily H.1213,Vaillancourt David6,Vidoni Eric5,Wang Wei‐en5,Mez Jesse14,Hohman Timothy J.15,Tosun Duygu16,Biber Sarah17,Kukull Walter A.17,Crane Paul K.2,Mormino Elizabeth C.118

Affiliation:

1. Department of Neurology and Neurological Sciences Stanford University Palo Alto California USA

2. Department of Medicine The University of Washington Seattle Washington USA

3. Department of Epidemiology and Population Health Stanford University Palo Alto California USA

4. Wisconsin Alzheimer's Disease Research Center University of Wisconsin School of Medicine and Public Health Madison Wisconsin USA

5. University of Kansas Alzheimer's Disease Center University of Kansas Medical Center Kansas City Kansas USA

6. Florida Alzheimer's Disease Research Center University of Florida Gainesville Florida USA

7. Alzheimer's Disease Research Center University of California Davis Health Davis California USA

8. Cleveland Alzheimer's Disease Research Center Cleveland Ohio USA

9. Healthy Aging & Alzheimer's Research Care (HAARC) Center, Department of Neurology University of Chicago Chicago Illinois USA

10. Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine Northwestern University Chicago Illinois USA

11. Indiana Alzheimer's Disease Research Center Indiana University School of Medicine Indianapolis Indiana USA

12. Department of Psychiatry and Behavioral Science University of Washington Seattle Washington USA

13. Geriatric Research Education and Clinical Center VA Puget Sound Health Care System Seattle Washington USA

14. Department of Neurology Boston University Boston Massachusetts USA

15. Vanderbilt Memory and Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USA

16. Department of Radiology and Biomedical Imaging University of California San Francisco California USA

17. Department of Epidemiology, National Alzheimer's Coordinating Center University of Washington Seattle Washington USA

18. Wu Tsai Neuroscience Institute Stanford California USA

Abstract

AbstractINTRODUCTIONAmyloid positron emission tomography (PET) is increasingly available for diagnosis of Alzheimer`s disease (AD); however, its practical implications in heterogenous cohorts are debated.METHODSAmyloid PET from 890 National Alzheimer`s Coordinating Center participants with up to 10 years post‐PET follow up was analyzed. Cox proportional hazards and linear mixed models were used to investigate amyloid burden prediction of etiology and prospective functional status and cognitive decline.RESULTSAmyloid positivity was associated with progression from unimpaired to mild cognitive impairment and dementia. Amyloid burden in the unimpaired group was associated with lower initial memory levels and faster decline in memory, language, and global cognition. In the Impaired group, amyloid was associated with lower initial levels and faster decline for memory, language, executive function, and global cognition.DISCUSSIONAmyloid burden is an important prognostic marker in a clinically heterogeneous cohort. Future work is needed to establish the proportion of decline driven by AD versus non‐AD processes in the context of mixed pathology.Highlights Our findings highlight the importance of amyloid positron emission tomography (PET) in heterogenous cohorts, including diverse demographics, clinical syndromes, and underlying etiologies. The results also provide evidence that higher amyloid levels were linked to functional progression from unimpaired cognition to mild cognitive impairment (MCI) and from MCI to dementia. In cognitively unimpaired individuals, higher amyloid burden was associated with poorer memory at baseline and subsequent declines in memory, language, and global cognition. Among individuals with cognitive impairment, amyloid burden was associated with worse initial memory, language, executive function, and global cognition, and faster declines over time.

Funder

National Institutes of Health

National Institute on Aging

National Institute of Nursing Research

Alzheimer's Association

Publisher

Wiley

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