The effects of amyloid and tau on small vessel diseases across Alzheimer's Disease spectrum
Poster No:
248
Submission Type:
Late-Breaking Abstract Submission
Authors:
Keshuo Lin1, Wei Wen2, Perminder Sachdev1, Jiyang Jiang3
Institutions:
1University of New South Wales, Sydney, NSW, 2Centre for Healthy Brain Ageing, University of New South Wales, Sydney, NSW, 3Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales (UNSW), Sydney, New South Wales
First Author:
Co-Author(s):
Jiyang Jiang, PhD
Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales (UNSW)
Sydney, New South Wales
Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales (UNSW)
Sydney, New South Wales
Introduction:
Vascular contributions to cognitive impairment and dementia are increasingly recognized (Kapasi & Schneider, 2016; Zlokovic et al., 2020), yet the impact of amyloid and tau on this relationship remains unclear. This study investigates both cross-sectional and longitudinal associations of amyloid and tau with cerebral blood flow (CBF) and volumes of white matter hyperintensities (WMH) in a cohort spanning cognitive normal (CN), mild cognitive impairment (MCI), and Alzheimer's Disease (AD).
Methods:
The current study included baseline data of 180 participants (97 CN, 63 MCI, 20 AD) from Alzheimer's Disease Neuroimaging Initiative 3 (ADNI3; (Weiner et al., 2017)), who have T1-weighted, T2-weighted FLAIR, and arterial spin labelling (ASL) acquired from GE scanners, as well as amyloid and tau PET data. Cerebral blood flow was quantified from ASL data after calibrating with M0 scans. WMH were automatically extracted by using UBO Detector (Jiang et al., 2018). Amyloid (cut-off SUVR: 1.11 for 18F-florbetapir, 1.08 for 18F-florbetaben) and tau (cut-off SUVR = 1.27) status were determined via PET imaging.
Results:
Amyloid and tau effects
Amyloid- and tau-positive individuals had higher WBWMH, PVWMH, and DWMH (p ≤ 0.008) than their negative counterparts. After adjusting for age, sex, and tau status, amyloid-positive individuals still showed higher DWMH volumes (mean difference = 2.42, p = 0.031). There were no significant differences in total GM CBF between amyloid-positive and amyloid-negative, or between tau-positive and tau-negative, participants. Higher CBF in temporal lobe was associated to lower tau in temporal lobe (β = -0.252, p = 0.027) after adjusting for age and sex.
Longitudinal analyses
WBWMH volumes increased over time (β = 0.098, p = 0.003), Changes in PVWMH and DWMH were not statistically significant (p = 0.054 and p = 0.147, respectively). A marginally significant interaction term between changes in WBWMH volumes and tau status (β = -0.089, p = 0.091) was found. When stratifying data by tau status, WBWMH volumes significantly increased over time in tau-negative (β = 0.091, p = 0.005), but not tau-positive (β = -0.005, p = 0.936), individuals.
Total GM CBF decreased across all lobes except for the frontal lobe (β = -0.101 - -0.069, p = 0.004 - 0.046), while no significant longitudinal change was observed for total WM CBF (including WMH and NAWM). Higher baseline tau was associated with a greater decrease in total GM CBF across all lobar regions (β = -0.285 - -0.137, p < 0.046). In contrast, higher baseline tau (β = 0.122 - 0.195, p = 0.002 - 0.008) and 18F-florbetapir amyloid (β = 0.277 - 0.321, p = 0.003 – 0.008) was associated with a greater increase in WBWMH, PVWMH, and DWMH volumes. Higher baseline WBWMH volumes were associated with a greater decline in total GM CBF (β = -0.123, p = 0.014), while lower baseline total GM CBF was associated with a greater increase in WBWMH (β = -0.114, p = 0.021).
Amyloid- and tau-positive individuals had higher WBWMH, PVWMH, and DWMH (p ≤ 0.008) than their negative counterparts. After adjusting for age, sex, and tau status, amyloid-positive individuals still showed higher DWMH volumes (mean difference = 2.42, p = 0.031). There were no significant differences in total GM CBF between amyloid-positive and amyloid-negative, or between tau-positive and tau-negative, participants. Higher CBF in temporal lobe was associated to lower tau in temporal lobe (β = -0.252, p = 0.027) after adjusting for age and sex.
Longitudinal analyses
WBWMH volumes increased over time (β = 0.098, p = 0.003), Changes in PVWMH and DWMH were not statistically significant (p = 0.054 and p = 0.147, respectively). A marginally significant interaction term between changes in WBWMH volumes and tau status (β = -0.089, p = 0.091) was found. When stratifying data by tau status, WBWMH volumes significantly increased over time in tau-negative (β = 0.091, p = 0.005), but not tau-positive (β = -0.005, p = 0.936), individuals.
Total GM CBF decreased across all lobes except for the frontal lobe (β = -0.101 - -0.069, p = 0.004 - 0.046), while no significant longitudinal change was observed for total WM CBF (including WMH and NAWM). Higher baseline tau was associated with a greater decrease in total GM CBF across all lobar regions (β = -0.285 - -0.137, p < 0.046). In contrast, higher baseline tau (β = 0.122 - 0.195, p = 0.002 - 0.008) and 18F-florbetapir amyloid (β = 0.277 - 0.321, p = 0.003 – 0.008) was associated with a greater increase in WBWMH, PVWMH, and DWMH volumes. Higher baseline WBWMH volumes were associated with a greater decline in total GM CBF (β = -0.123, p = 0.014), while lower baseline total GM CBF was associated with a greater increase in WBWMH (β = -0.114, p = 0.021).
Conclusions:
Cross-sectional results showed that CBF was associated with classification, which is mainly determined by cognitive performance. However, WMH burden was associated with amyloid and tau pathology. Tau-negative individuals had lower WBWMH volumes at baseline, but greater increase over time, compared to tau-positive counterparts. These findings highlight the interaction between amyloid, tau, and small vessel diseases in AD spectrum.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Modeling and Analysis Methods:
Task-Independent and Resting-State Analysis 2
Keywords:
Other - White Matter Hyperintensities, Cerebral Blood Flow, Tau, Amyloid
1|2Indicates the priority used for review
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Provide references using APA citation style.
Kapasi, A. (2016). Vascular contributions to cognitive impairment, clinical Alzheimer's disease, and dementia in older persons. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1862(5), 878-886. https://doi.org/10.1016/j.bbadis.2015.12.023
Weiner, M. W. (2017). The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 13(5), 561-571. https://doi.org/10.1016/j.jalz.2016.10.006
Zlokovic, B. V. (2020). Vascular contributions to cognitive impairment and dementia (VCID): A report from the 2018 National Heart, Lung, and Blood Institute and National Institute of Neurological Disorders and Stroke Workshop. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 16(12), 1714-1733. https://doi.org/10.1002/alz.12157