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.

Background

The association between omega-3 (ω-3) PUFAs and cognition, brain imaging and biomarkers is still not fully established.

Objectives

The aim was to analyze the cross-sectional and retrospective longitudinal associations between erythrocyte ω-3 index and cognition, brain imaging, and biomarkers among older adults.

Methods

A total of 832 Alzheimer's Disease Neuroimaging Initiative 3 (ADNI-3) participants, with a mean (SD) age of 74.0 (7.9) y, 50.8% female, 55.9% cognitively normal, 32.7% with mild cognitive impairment, and 11.4% with Alzheimer disease (AD) were included. A low ω-3 index (%EPA + %DHA) was defined as the lowest quartile (≤3.70%). Cognitive tests [composite score, AD Assessment Scale Cognitive (ADAS-Cog), Wechsler Memory Scale (WMS), Trail Making Test, Category Fluency, Mini-Mental State Examination, Montreal Cognitive Assessment] and brain variables [hippocampal volume, white matter hyperintensities (WMHs), positron emission tomography (PET) amyloid-β (Aβ) and tau] were considered as outcomes in regression models.

Results

Low ω-3 index was not associated with cognition, hippocampal, and WMH volume or brain Aβ and tau after adjustment for demographics, ApoEε4, cardiovascular disease, BMI, and total intracranial volume in the cross-sectional analysis. In the retrospective analysis, low ω-3 index was associated with greater Aβ accumulation (adjusted β = 0.02; 95% CI: 0.01, 0.03; P = 0.003). The composite cognitive score did not differ between groups; however, low ω-3 index was significantly associated with greater WMS-delayed recall cognitive decline (adjusted β = -1.18; 95% CI: -2.16, -0.19; P = 0.019), but unexpectedly lower total ADAS-Cog cognitive decline. Low ω-3 index was cross-sectionally associated with lower WMS performance (adjusted β = -1.81, SE = 0.73, P = 0.014) and higher tau accumulation among ApoE ε4 carriers.

Conclusions

Longitudinally, low ω-3 index was associated with greater Aβ accumulation and WMS cognitive decline but unexpectedly with lower total ADAS-Cog cognitive decline. Although no associations were cross-sectionally found in the whole population, low ω-3 index was associated with lower WMS cognition and higher tau accumulation among ApoE ε4 carriers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is registered at clinicaltrials.gov as NCT00106899.