Abstract Details

Title One Hundred Centenarians: Brain Pathology and Relationship to Dementia in The 90+ Study

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 028

Objective To determine prevalence of dementia-related neuropathologic changes and examine their association with dementia risk and severity in centenarians, and compare findings with nonagenarians from the same cohort.

Background Centenarians worldwide are projected to increase 50-fold by 2100 with dementia incidence estimated ~40%. Brain autopsy studies in this population are highly limited.

Design/Methods Participants were individuals who agreed to autopsy from The 90+ Study, a longitudinal study of aging. Cognitive diagnoses were assigned during a multidisciplinary conference blinded to autopsy results. Using standardized protocols, dementia-related neuropathologic changes (NCs) were assessed blinded to clinical information and dichotomized for analyses: +Alzheimer’s disease (AD) neuropathologic change (ADNC;intermediate/high), +cerebral amyloid angiopathy (moderate/severe), +arteriosclerosis (moderate/severe), +Lewy body disease (limbic/neocortical), +TDP-43 (hippocampal/cortical), +age-related tau astrogliopathy (ARTAG;present), +microinfarcts (≥2), and +hippocampal sclerosis (present). Mini-Mental State Exam (MMSE) scores nearest to death were used to examine dementia severity. Prevalence and associated odds of dementia were determined for each NC and for the presence of multiple NCs.

Results 388 participants (100 centenarians and 288 nonagenarians) with completed brain autopsies were included. In centenarians, ADNC was most prevalent (75%; vs. 71% in nonagenarians), followed by arteriosclerosis (69%; vs. 55% in nonagenarians) and ARTAG (66%; vs. 60% in nonagenarians). In centenarians, arteriosclerosis (69%) and TDP-43 (39%) were significantly more prevalent compared to nonagenarians (55% and 28% respectively; P=0.01 and P=0.05 respectively). 83% centenarians had 2+NCs and number of NCs was strongly associated with dementia risk. Odds ratio increased from 2.9 (95% Confidence interval (CI):0.49-16.9) for 2NCs, to 12.7 (95%CI:2.34-68.31) for 3, and 63.8 (95%CI:8.78-463.67) for 4NCs. Number of NCs was also associated with dementia severity.

Conclusions Prevalence of dementia-related NCs is exceptionally high in centenarians and greater for arteriosclerosis and TDP-43 compared to nonagenarians. Multiple NCs are typical in centenarians and strongly associated with cognitive impairment, with risk and severity increasing with higher numbers of NCs.

Authors/Disclosures
Raumin S. Neuville, MD PRESENTER	Mr. Neuville has received research support from University of California, Irvine, School of Medicine.
	No disclosure on file
S. Ahmad Sajjadi, MD, PhD, MRCP, FAAN (University of California, Irvine)	Dr. Sajjadi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GUIDEPOINT. Dr. Sajjadi has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Alzheimer Research and Therapy. The institution of Dr. Sajjadi has received research support from NIH.
	No disclosure on file
Thomas J. Montine, MD, PhD	Dr. Montine has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Enable Medicine. Dr. Montine has stock in Enable Medicine. The institution of Dr. Montine has received research support from NIH. The institution of Dr. Montine has received research support from MJFF. Dr. Montine has received intellectual property interests from a discovery or technology relating to health care. Dr. Montine has received publishing royalties from a publication relating to health care.
Maria Corrada, PhD (University of California Irvine)	The institution of Dr. Corrada has received research support from NIH.
Claudia Kawas, MD (University of California, Irvine)	The institution of Dr. Kawas has received research support from NIH.

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