Clinical and anatomical correlates of gait dysfunction in Alzheimer's disease

We conducted a cross-sectional study to investigate the clinical and anatomical correlates of gait dysfunction in advanced Alzheimer's disease (AD). A comprehensive clinical protocol that included cognitive, functional, behavioral, and motor variables was administered to patients with probable AD (n = 100), possible AD (n = 17), and AD with cerebrovascular disease (AD + CVD) (n = 27). Gait dysfunction was evaluated with the Rating Scale for Gait Evaluation in Cognitive Deterioration and magnetic resonance imaging was analyzed in 94 patients (volumetry study) and 78 patients (diffusion tensor imaging study). Univariate correlations, multivariate regression, and statistical parametric mapping analyses were conducted in the total sample and in the subsample of patients with probable AD. Mean age was 82.5 (SD 6.3, range 56 to 98), 83.3% were female patients, and 95.1% displayed moderate to severe dementia. Parkinsonism, patient setting (nursing home), dementia severity, apathy, and (worse) cognitive performance significantly predicted gait dysfunction in the total sample (p < 0.05, R(2) = 0.58), whereas parkinsonism, patient setting, and limb weakness due to non-AD conditions predicted gait dysfunction in probable AD (p < 0.05, R(2) = 0.57). Gait dysfunction was related to atrophy in the motor cortex, the middle cingulate, the anterior insula, the right caudate (total sample only), and the anterior lobe of the cerebellum (p < 0.01, corrected). Significant correlations were also observed between gait dysfunction and damage in several white matter locations (p < 0.001, uncorrected). The present results are congruent with a model of multi-system gray matter degeneration, with progressive damage to critical regions (i.e., motor cortex, cingulate, insula, and cerebellum) producing gait dysfunction and, eventually, gait loss in AD.