Contributions of amyloid beta and cerebral small vessel disease in clinical decline.

INTRODUCTION: We assessed whether co-morbid small vessel disease (SVD) has clinical predictive value in preclinical or prodromal Alzheimer's disease. METHODS: In 1090 non-demented participants (65.4 ± 10.7 years) SVD was assessed with magnetic resonance imaging and amyloid beta (Aß) with lumbar puncture and/or positron emission tomography scan (mean follow-up for cognitive function 3.1 ± 2.4 years). RESULTS: Thirty-nine percent had neither Aß nor SVD (A-V-), 21% had SVD only (A-V+), 23% Aß only (A+V-), and 17% had both (A+V+). Pooled cohort linear mixed model analyses demonstrated that compared to A-V- (reference), A+V- had a faster rate of cognitive decline. Co-morbid SVD (A+V+) did not further increase rate of decline. Cox regression showed that dementia risk was modestly increased in A-V+ (hazard ratio [95% confidence interval: 1.8 [1.0-3.2]) and most strongly in A+ groups. Also, mortality risk was increased in A+ groups. DISCUSSION: In non-demented persons Aß was predictive of cognitive decline, dementia, and mortality. SVD modestly predicts dementia in A-, but did not increase deleterious effects in A+. HIGHLIGHTS: Amyloid beta (Aß; A) was predictive for cognitive decline, dementia, and mortality. Small vessel disease (SVD) had no additional deleterious effects in A+. SVD modestly predicted dementia in A-. Aß should be assessed even when magnetic resonance imaging indicates vascular cognitive impairment.

The laser shoes: A new ambulatory device to alleviate freezing of gait in Parkinson disease.

OBJECTIVE: To assess, in a cross-sectional study, the feasibility and immediate efficacy of laser shoes, a new ambulatory visual cueing device with practical applicability for use in daily life, on freezing of gait (FOG) and gait measures in Parkinson disease (PD). METHODS: We tested 21 patients with PD and FOG, both "off" and "on" medication. In a controlled gait laboratory, we measured the number of FOG episodes and the percent time frozen occurring during a standardized walking protocol that included FOG provoking circumstances. Participants performed 10 trials with and 10 trials without cueing. FOG was assessed using offline video analysis by an independent rater. Gait measures were recorded in between FOG episodes with the use of accelerometry. RESULTS: Cueing using laser shoes was associated with a significant reduction in the number of FOG episodes, both "off" (45.9%) and "on" (37.7%) medication. Moreover, laser shoes significantly reduced the percent time frozen by 56.5% (95% confidence interval [CI] 32.5-85.8; p = 0.004) when "off" medication. The reduction while "on" medication was slightly smaller (51.4%, 95% CI -41.8 to 91.5; p = 0.075). These effects were paralleled by patients' positive subjective experience on laser shoes' efficacy. There were no clinically meaningful changes in the gait measures. CONCLUSIONS: These findings demonstrate the immediate efficacy of laser shoes in a controlled gait laboratory, and offer a promising intervention with potential to deliver in-home cueing for patients with FOG. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with PD, laser shoes significantly reduce FOG severity (both number and duration of FOG episodes).