Skeletal muscle mitochondrial function predicts cognitive impairment and is associated with biomarkers of Alzheimer's disease and neurodegeneration
Qu Tian, Murat Bilgel, Keenan A. Walker, Abhay R. Moghekar, Kenneth W. Fishbein, Richard G. Spencer, Susan M. Resnick, Luigi Ferrucci- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
INTRODUCTION
Mitochondrial dysfunction is implicated in the pathophysiology of many chronic diseases. Whether it is related to cognitive impairment and pathological markers is unknown.
METHODS
We examined the associations of in vivo skeletal muscle mitochondrial function (post‐exercise recovery rate of phosphocreatine [kPCr] via magnetic resonance [MR] spectroscopy with future mild cognitive impairment (MCI) or dementia, and with positron emission tomography (PET) and blood biomarkers of Alzheimer's disease [AD] and neurodegeneration (i.e., Pittsburgh Compound‐B [PiB] distribution volume ratio [DVR] for amyloid beta [Aβ], flortaucipir (FTP) standardized uptake value ratio [SUVR] for tau, Aβ42/40 ratio, phosphorylated tau 181 [p‐tau181], neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]).
RESULTS
After covariate adjustment, each standard deviation (SD) higher kPCr level was associated with 52% lower hazards of developing MCI/dementia, and with 59% lower odds of being PiB positive with specific associations in DVR of frontal, parietal, and temporal regions, and cingulate cortex and pallidum. Higher kPCr level was also associated with lower plasma GFAP.
DISCUSSION
In aging, mitochondrial dysfunction may play a vital role in AD pathological changes and neuroinflammation.
Highlights
Higher in vivo mitochondrial function is related to lower risk of mild cognitive impairment (MCI)/dementia. Higher in vivo mitochondrial function is related to lower amyloid tracer uptake. Higher in vivo mitochondrial function is related to lower plasma neuroinflammation. Mitochondrial dysfunction may play a key role in Alzheimer's disease (AD) and neurodegeneration.