White matter hyperintensities and neuropsychiatric symptoms in mild cognitive impairment and Alzheimer’s disease

Neuropsychiatric symptoms (NPS), such as apathy, irritability and depression, are frequently encountered in patients with Alzheimer’s disease (AD). Focal grey matter atrophy has been linked to NPS development. Cerebrovascular disease is common among AD patients and can be detected on MRI as white matter hyperintensities (WMH). In this longitudinal study, the relative contribution of WMH burden and GM atrophy to NPS was evaluated in a cohort of mild cognitive impairment (MCI), AD and normal controls. This study included 121 AD, 315 MCI and 225 normal control subjects from the Alzheimer’s Disease Neuroimaging Initiative. NPS were assessed using the Neuropsychiatric Inventory and grouped into hyperactivity, psychosis, affective and apathy subsyndromes. WMH were measured using an automatic segmentation technique and mean deformation-based morphometry (DBM) was used to measure atrophy of grey matter regions. Linear mixed-effects models found focal grey matter atrophy and WMH volume both contributed significantly to NPS subsyndromes in MCI and AD subjects, however, WMH burden played a greater role. This study could provide a better understanding of the pathophysiology of NPS in AD and support the monitoring and control of vascular risk factors.