Mary M. Machulda, United States of America
Mayo Clinic Psychiatry and PsychologyAuthor Of 1 Presentation
ASSOCIATION BETWEEN TDP-43 STAGE AND RATE OF MEMORY, FUNCTIONAL AND GLOBAL COGNITIVE DECLINE
Abstract
Aims
To determine whether cross-sectional and longitudinal cognitive and functional decline are associated with spread of transactive response DNA-binding protein of 43kDa (TDP-43) in the brain.
Methods
Longitudinal clinical-neuropathologic autopsy cohort study of 385 initially cognitively normal/mildly impaired older adults prospectively followed until death. Associations between TDP-43, amyloid-beta, tau neurofibrillary tangles (NFT), age, sex, genetics and clinical and neuropsychological scores and rates of their decline were investigated.
Results
Of 385 participants, 260 (68%) had no TDP-43 depoistion, 32(8%) had TDP-43 limited to amygdala, and 93(24%) had TDP-43 in the hippocampus and beyond. TDP-43-positive patients had higher frequency of APOE ε4 allele, neuritic plaque score and Braak NFT stage compared to TDP-43 negative patients; they were also less likely to remain cognitively normal at last examination, p<0.0001. Higher TDP-43 and Braak NFT stages independently were associated with faster decline in global cognition, functional performance, naming and episodic memory, whereas older age was associated with slower rates of cognitive, and functional decline. Cross-sectionally, higher TDP-43 and Braak NFT stages were associated with worse performance in the same measures as longitudinally observed (Figure 1). We also found higher amyloid-beta burden to be associated with worse global cognition and a higher frequency of behavioral changes. There were no associations with the APOE ε4 allele (Figure 1).
Conclusions
The associations between TDP-43 and faster rates of cognitive and functional performance over time suggests that TDP-43 is likely playing a role in the clinical progression to dementia, as is the case for tau.