Cerebral white matter disease is independently associated with BPSD in Alzheimer's disease

Objectives: To study the association between cerebral white matter disease and burden of behavioral and psychological symptoms (BPSD) among patients with moderate to severe AD.

Methods: Patients with moderate to severe AD having undergone MRI brain, cognitive and behavioral evaluations were studied. BPSD was diagnosed based on established clinical guidelines. White matter hyperintensity (WMH) and medial temporal lobe atrophy (MTA) were quantified by a blinded rater.

Results: 122 AD patients were studied. Age [76.84 vs. 72.70, p = 0.014] and MMSE [11.69 vs. 15.16, p < 0.001] was significantly higher in patients with BPSD. BPSD patients demonstrated higher periventricular [5.44 vs. 4.21, p < 0.001], deep subcortical [5.07 vs. 3.43, p < 0.001], and total WMH [10.51 vs. 7.65, p < 0.001] compared to non-BPSD patients. Higher proportion of BPSD patients had WMH in the highest tertile of severity (82.22% vs. 45.45%, p < 0.001). After correcting for age, baseline cognition and degree of MTA, total WMH remained significantly associated with a diagnosis of BPSD [odds ratio: 1.45 (1.14-1.85; p = 0.002)]. With severe WMH, the association is significantly increased [odds ratio: 4.3 (1.3-12.5); p = 0.016].

Conclusion: WMH is independently associated with BPSD in moderate to severe AD. Optimizing vascular risk factors may be a strategy to reduce the severity of BPSD in AD.