ABSTRACT
INTRODUCTION: Motor function has correlated with longevity and functionality; however, there is limited research on those with Alzheimer's disease (AD). We studied the association between motor functionality and AD pathology in primary motor and medial temporal cortices. METHODS: A total of 206 participants with a clinical diagnosis of cognitively healthy, AD, or mild cognitive impairment (MCI) underwent imaging and motor assessment. Linear regressions and analyses of variance were applied to test the prediction from AD imaging biomarkers to motor performance and the diagnosis group differences in motor performance. RESULTS: Increased neurodegeneration was associated with worsening dexterity and lower walking speed, and increased amyloid and tau were associated with worsening dexterity. AD and MCI participants had lower motor performance than the cognitively healthy participants. DISCUSSION: Increased AD pathology is associated with worsening dexterity performance. The decline in dexterity in those with AD pathology may offer an opportunity for non-pharmacological therapy intervention. HIGHLIGHTS: Noted worsening dexterity performance was associated with greater Alzheimer's disease (AD) pathology (tau, amyloid beta, and neurodegeneration) in primary motor cortices. Similarly, increased neurodegeneration and tau pathology in parahippocampal, hippocampal, and entorhinal cortices is associated with worsening dexterity performance. Motor performance declined in those with clinical and preclinical AD among an array of motor assessments.
Subject(s)
Alzheimer Disease , Biomarkers , Cognitive Dysfunction , Motor Cortex , Humans , Alzheimer Disease/physiopathology , Male , Female , Aged , Motor Cortex/physiopathology , Motor Cortex/diagnostic imaging , Cognitive Dysfunction/physiopathology , tau Proteins/cerebrospinal fluid , Magnetic Resonance Imaging , Amyloid beta-Peptides/metabolism , Aged, 80 and over , Positron-Emission Tomography , Neuropsychological Tests/statistics & numerical dataABSTRACT
OBJECTIVE: Insulin regulates metabolism and influences neural health. Insulin resistance (IR) and type II diabetes have been identified as risk factors for Alzheimer disease (AD). Evidence has also suggested that myelinated white matter alterations may be involved in the pathophysiology of AD; however, it is unknown whether insulin or IR affect the underlying myelin microstructure. The relationships between insulin, IR, and myelin were examined, with the hypothesis that IR would be associated with reduced myelin. METHODS: Cognitively unimpaired adults enriched for risk factors for AD underwent multicomponent driven equilibrium single pulse observation of T1 and T2 imaging, a myelin-sensitive neuroimaging technique. Linear regressions were used to test the relationship between homeostatic model assessment of IR, insulin, and myelin water fraction (MWF) as well as interactions with APOE ε4. RESULTS: Both IR and insulin level were associated with altered myelin content, wherein a significant negative association with MWF was observed in white matter regions and a positive association with MWF was observed in gray matter. CONCLUSIONS: The results suggest that insulin and IR influence white matter myelination in a cognitively unimpaired population. Additional studies are needed to determine the extent to which this may contribute to cognitive decline or vulnerability to neurodegenerative disease.