Effect of physical activity on progression of cerebrovascular disease in older adults at risk or alzheimer's disease

Abstract

Objective: Alzheimer's disease (AD) is a form of dementia without cure. Dementias are the only condition out of the top 10 causes of mortality worldwide without cure and represent a significant health burden. White matter hyperintensities (WMH) are a biomarker of brain white matter disease, and are associated with a number of neuropsychiatric disorders including dementia. WMH progression has been shown to be reduced by vascular risk factor (VRF) control. Physical activity (PA) has also been shown to slow the progression of WMH, control VRF related disease and has also been shown to reduce cognitive decline. It is therefore postulated that PA can slow WMH progression and could perhaps be a lifestyle related treatment that slows cognitive decline, which would have great public health implications. Conventional manual segmentation (CMS) is the current gold standard in WMH volumetry. Side-by-side (SBS) segmentation has shown promise in WMH visual rating scales and other areas in radiology but has not yet been applied to manual segmentation of WMH lesions.

We hypothesise that PA slows WMH progression, and this progression is slower in ApoE ε4 and PET Amyloid beta status negative patients. We also hypothesise that there is a concomitant positive association between baseline cognition measures and WMH progression. Finally, we hypothesise that side by side segmentation will give WMH volumes with more significant clinical associations than the traditional segmentation methods.

Method: Data was obtained as part of the AIBL Active trial. Participants are older adults at risk of AD with at least one VRF. Imaging data was obtained on a Siemens 3T Tim Trio scanner. Images were processed according to accepted standards, with FLAIR images used for WMH volumetry, and MPRAGE images used to obtain estimated total intracranial volume (ETIV). WMH were manually segmented under expert neuroradiologist guidance (A/Prof P. Phal), firstly obtaining CMS volumes and then SBS volumes. These volumes were corrected for ETIV and log transformed, then compared against age, gender, VRF, baseline functional fitness, Years of education, cognitive group (SMC/MCI) and baseline neurocognitive assessments using correlations, and subsequently general linear models.

Results: In older adults at risk of AD with at least one VRF, exercise over a 24 month period was not associated with a slowing of WMH progression. There was also no association between baseline functional fitness assessment and WMH progression. ApoE ε4 and PET Amyloid beta status were also not associated with a slowing of WMH progression. We did find correlations between WMH volume and age with both methods, with baseline WMH significantly predicting progression. Systolic blood pressure was also associated with WMH progression in correlations in the CMS general linear model. Anxiety was inversely associated with WMH progression while other cognitive measures were not. Side-by-side manual segmentation did not result in significant clinical differences compared to conventional manual segmentation.

Conclusion: Based on our results we were unable to show effectiveness of physical activity in older adults at risk of AD in slowing WMH progression. We also cannot conclude that SBS WMH segmentation is more effective than accepted methods.