Relationship of regional brain β-amyloid to gait speed

Abstract

Objective: To investigate in vivo the relationship of regional brain β-amyloid (Aβ) to gait speed in a group of elderly individuals at high risk for dementia.

Methods: Cross-sectional associations between brain Aβ as measured with [18F]florbetapir PET and gait speed were examined in 128 elderly participants. Subjects ranged from healthy to mildly cognitively impaired enrolled in the control arm of the multidomain intervention in the Multidomain Alzheimer Preventive Trial (MAPT). Nearly all participants presented spontaneous memory complaints. Regional [18F]florbetapir (AV45) standardized uptake volume ratios were obtained via semiautomated quantitative analysis using the cerebellum as reference region. Gait speed was measured by timing participants while they walked 4 meters. Associations were explored with linear regression, correcting for age, sex, education, body mass index (BMI), and APOE genotype.

Results: We found a significant association between Aβ in the posterior and anterior putamen, occipital cortex, precuneus, and anterior cingulate and slow gait speed (all corrected p < 0.05). A multivariate model emphasized the locations of the posterior putamen and the precuneus. Aβ burden explained up to 9% of the variance in gait speed, and significantly improved regression models already containing demographic variables, BMI, and APOE status.

Conclusions: The present PET study confirms, in vivo, previous postmortem evidence showing an association between Alzheimer disease (AD) pathology and gait speed, and provides additional evidence on potential regional effects of brain Aβ on motor function. More research is needed to elucidate the neural mechanisms underlying these regional associations, which may involve motor and sensorimotor circuits hitherto largely neglected in the pathophysiology of AD.

Figure 1. Flowchart describing the participants/excluded in the current study

MAPT = Multidomain Alzheimer Preventive Trial.

Figure 2. Regression coefficients (B) of regional amyloid levels on gait speed

Error bars represent 95% confidence intervals (CI). Results are corrected for age, sex, education, body mass index, APOE status, time of enrollment in study at PET visit, and time between PET visit and closest gait speed assessment. Striatal regions are indicated with darker markers. The right column provides means and SDs of regional florbetapir standard uptake value ratios (SUVRs). Associations that remained significant after multiple comparisons are indicated with an asterisk (all corrected p < 0.05).