Â鶹´«Ã½Ó³»­

Â鶹´«Ã½Ó³»­

Explore the latest content from across our publications
Join The Â鶹´«Ã½Ó³»­

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Amyloid, Tau and Metabolic Correlates of Cognition in Early and Late-Onset Alzheimer’s Disease
Aging, Dementia, and Behavioral Neurology
Aging and Dementia Posters (7:00 AM-5:00 PM)
041
To characterize and compare the associations between PET-based molecular pathology and domain-specific cognitive performance in early-onset(EOAD, age<65) versus late-onset Alzheimer’s disease(LOAD, age≥65).
Tau, amyloid and neurodegeneration have different associations with cognition in AD. These associations may differ between EOAD and LOAD.
Amyloid-positive participants with mild cognitive impairment or AD dementia(EOAD n=60, mean age 58±4, MMSE 21±6, 58% female; LOAD n=53, mean age 74±6, MMSE 23±5, 45% female) underwent 18F-flortaucipir(FTP-PET, tau, n=113), 11C-PIB-PET(PIB-PET, amyloid-β, n=113), and 18F-fluorodeoxyglucose-PET(FDG-PET, glucose metabolism, n=84). Composite scores for episodic memory, semantic memory, language, executive function and visuospatial domains were calculated based on neuropsychological testing. Voxelwise regressions evaluated correlations between PET modalities and cognitive scores in each age group and the total sample, including PET x age group interaction in the model(all thresholded at uncorrected p<0.001 voxel-level, FWE p<0.05 cluster-level). Mediation analyses estimated direct and indirect(FDG-PET mediated) associations between FTP-PET and cognitive scores in regions-of-interest. 
EOAD had higher FTP-PET binding in parietal, lateral temporal, and lateral frontal cortex; more severe FDG-PET hypometabolism in the precuneus and angular gyrus; and greater PIB-PET binding in occipital lobes compared to LOAD. FTP-PET and FDG-PET, but not PIB-PET, were significantly associated with cognition in expected domain-specific patterns in both age groups(e.g., perisylvian/language, frontal/executive, occipital/visuospatial). In the entire cohort, there was no significant interaction between age and PET modalities. Mediation analysis revealed FDG-PET mediated the relationship between FTP-PET and cognition in both age groups across all domains except LOAD episodic memory. In EOAD, additional direct effects of FTP-PET were observed in semantic memory(p=0.046) and language(p=0.02). 
Tau and neurodegeneration, but not amyloid, were associated with cognition in EOAD and LOAD. Tau had a greater association with cognition independent of neurodegeneration in EOAD, suggesting greater tau neurotoxicity and/or fewer co-pathologies contributing to symptoms. Anti-tau therapeutics may slow cognitive decline in both EOAD and LOAD. 
Authors/Disclosures
Jeremy Tanner, MD (UTHSA - Neurology)
PRESENTER 		An immediate family member of Dr. Tanner has received personal compensation for serving as an employee of Channeling Hope Foundation. The institution of Dr. Tanner has received research support from NIA, NINDS. Dr. Tanner has a non-compensated relationship as a Chief Scientific Officer with Channeling Hope Foundation that is relevant to Â鶹´«Ã½Ó³»­ interests or activities.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
David N. Soleimani-Meigooni, MD (University of California, San Francisco) Dr. Soleimani-Meigooni has nothing to disclose.
Howard J. Rosen, MD (UCSF) Dr. Rosen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly . Dr. Rosen has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alector. The institution of Dr. Rosen has received research support from NIH. The institution of Dr. Rosen has received research support from State of CA. Dr. Rosen has a non-compensated relationship as a Consultant with Prevail Therapeutics that is relevant to Â鶹´«Ã½Ó³»­ interests or activities. Dr. Rosen has a non-compensated relationship as a consultant with Alchemab that is relevant to Â鶹´«Ã½Ó³»­ interests or activities.
Joel Kramer, PhD (UCSF Medical Center) The institution of Dr. Kramer has received research support from tau consortium. Dr. Kramer has received publishing royalties from a publication relating to health care.
Bruce L. Miller, MD, FÂ鶹´«Ã½Ó³»­ (University of California, San Francisco) Dr. Miller has nothing to disclose.
Gil D. Rabinovici, MD, FÂ鶹´«Ã½Ó³»­ (UCSF Memory & Aging Center) Dr. Rabinovici has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alector. Dr. Rabinovici has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novo Norodisk. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for C2N. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Johnson & Joihnson. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Peerview. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medscape. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA. The institution of Dr. Rabinovici has received research support from NIH. The institution of Dr. Rabinovici has received research support from American College of Radiology. The institution of Dr. Rabinovici has received research support from Alzheimer's Association. The institution of Dr. Rabinovici has received research support from Rainwater Charitable Foundation. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Topic Chair, Course Director and teacher with Â鶹´«Ã½Ó³»­. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Grant reviewer with NIH. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Invited speaker with ANA.