Abstract Details

Title TDP-43 Is as Important as Alzheimer’s Disease Neuropathology in the Oldest Old

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) S23 - Aging and Dementia: Biomarkers and Clinical Trials (4:18 PM-4:30 PM)

Poster/Presentation
Number 005

Objective

To highlight the high prevalence of TDP-43 pathology, also known as limbic predominant age related TDP-43 encephalopathy (LATE), and its strong association with dementia in the oldest old.

Background The oldest old are the fastest growing segment of our population with the highest prevalence of dementia. By year 2050, more than 50% of dementia sufferers in the US will belong to this age group. TDP-43 pathology is a frequent but less studied pathology in this age. We describe findings from The 90+ Study, a longitudinal clinical and autopsy study of participants aged 90 years and older, that shows TDP-43 pathology might be as important as Alzheimer's disease (AD) in this age.

Design/Methods 241 participants of the 90+ study with comprehensive clinical, neuropsychology, and neuropathology data were included. Dementia status, clinical syndrome, and impaired cognitive domains were determined at multi-disciplinary post-mortem conferences blind to autopsy data. AD neuropathology (ADNP) was defined as CERAD score for neuritic plaques ≥2 and Braak stage for neurofibrillary tangles ≥5. TDP-43 pathology was considered present in those with at least amygdala and hippocampal TDP-43. Logistic regression analyses adjusting for age, sex, and education, explored the association between ADNP, TDP-43, and dementia, clinical diagnosis of AD, and memory impairment.

Results 125 participants (52%) died with dementia (Mean age at death: 98.1, 75% female). Of these, 33% had TDP-43 and 40% had ADNP. TDP-43 was as important a predictor of dementia and clinical diagnosis of AD at death as ADNP (For dementia outcome: TDP-43 OR: 3.0 vs. ADNP OR: 2.6; For clinical AD outcome: TDP OR: 3.5 vs. ADNP OR: 3.4). Both pathologies independently predicted memory impairment (TDP-43 OR: 4.7; ADNP OR: 4.1).

Conclusions

Our results suggest TDP-43 pathology is as important as ADNP in people over 90, the age group that will have the greatest number of dementia sufferers.

Authors/Disclosures
S. Ahmad Sajjadi, MD, PhD, MRCP, FAAN (University of California, Irvine) PRESENTER	The institution of Dr. Sajjadi has received research support from NIH.
Maria Corrada, PhD (University of California Irvine)	The institution of Dr. Corrada has received research support from NIH.
	No disclosure on file
Claudia Kawas, MD (University of California, Irvine)	The institution of Dr. Kawas has received research support from NIH.

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