The Longitudinal Assessment of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Alzheimer's Disease and Their Association With White Matter Hyperintensities in the National Alzheimer's Coordinating Center's Uniform Data Set

Abstract

Background: Neuropsychiatric symptoms (NPSs) are common in Alzheimer's disease (AD). NPSs contribute to patients' distress, caregiver burden, and institutionalization. White matter hyperintensities (WMHs) appear on magnetic resonance imaging, usually indicative of cerebrovascular disease. WMHs have been associated with certain NPSs. We aimed to assess the relationship between WMH and NPS severity in mild cognitive impairment (MCI) due to AD (MCI-AD) and in AD and to assess the ability of WMHs to predict NPS progression. Data were obtained from the National Alzheimer's Coordinating Center.

Methods: A total of 252 participants (114 with MCI-AD and 138 with AD) were used in this study. Baseline WMHs were quantified using an automated segmentation technique. NPSs were measured using the Neuropsychiatric Inventory. Mixed-effect models and correlations were used to determine the relationship between WMHs and NPSs.

Results: Longitudinal mixed-effect models revealed a significant relationship between increase in Neuropsychiatric Inventory total scores and baseline WMHs (p = .014). There was a significant relationship between baseline WMHs and an increase in delusions (p = .023), hallucinations (p = .040), agitation (p = .093), depression (p = .017), and irritability (p = .002). Correlation plot analysis showed that baseline whole-brain WMHs predicted change in future Neuropsychiatric Inventory total scores (r = .169, p = .008) and predicted change in future agitation severity scores (r = .165, p = .009). WMHs in the temporal lobes (r = .169, p = .008) and frontal lobes (r = .153, p = .016) contributed most to this change.

Conclusions: Depression, irritability, and agitation are common NPSs and very distressful to patients and caregivers. Our findings of increased NPS severity over time in MCI-AD and AD with increased WMHs have important implications for treatment, arguing for aggressive treatment of vascular risk factors in patients with MCI-AD or AD.

Keywords: Alzheimer’s disease; Cerebrovascular disease; Mild cognitive impairment; Neuroimaging; Neuropsychiatric symptoms; White matter hyperintensities.

Figure 1.

Correlation plot of baseline whole brain WMH load to predict the change in future NPI total scores over time

Figure 2.

Correlation plots of baseline whole brain WMH load to predict the annualized change in future NPI severity scores over time, correcting for age, sex and education (without meds). From left to right: DELSEV = delusion severity score, HALLSEV = hallucination severity score, AGITSEV = agitation severity score, DEPD = depression severity score, ANXSEV = anxiety severity score, ELATSEV = elation severity score, APASEV = apathy severity score, DISNSEV = disinhibition severity score, IRRSEV = irritability severity score, MOTSEV = aberrant motor behaviour severity score, NITESEV = Night-time behaviour severity score, APPSEV = appetite severity score

Figure 3.

Correlation plots of baseline temporal and frontal lobe WMH load to predict the change in future agitation severity scores over time. AGITSEV = agitation severity score