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

ABSTRACTIntroductionNeuropsychiatric symptoms (NPS) are common in all dementias, including those with Alzheimer’s disease (AD). NPS contribute to patients’ distress, caregiver burden, and can lead to institutionalization. White matter hyperintensities (WMH) are a common finding on MRI usually indicative of cerebrovascular disease and have been associated with certain NPS. The aim of this study was two-fold. Firstly, we assessed the relationship between WMH load and NPS severity in MCI due to AD (MCI-AD) and AD. Secondly, we assessed the ability of WMH to predict the development and progression of NPS in these participants. Data was obtained from the National Alzheimer’s Coordinating Center.MethodsWMH were obtained from baseline MRIs and quantified using an automated segmentation technique. NPS were measured using the Neuropsychiatric Inventory (NPI). Mixed effect models and correlations were used to determine the relationship between WMH load and NPS severity scores.ResultsCross-sectional analysis showed no significant association between NPS and WMH at baseline. Longitudinal mixed effect models, however, revealed a significant relationship between increase in NPI total scores and baseline WMH load (p=0.014). There was also a significant relationship between increase in irritability severity scores over time and baseline WMH load (p= 0.009). Trends were observed for a relationship between increase in agitation severity scores and baseline WMH load (p=0.058). No other NPS severity scores were significantly associated with baseline WMH load. The correlation plot analysis showed that baseline whole brain WMH predicted change in future NPI total scores (r=0.169, p=0.008). Baseline whole brain WMH also predicted change in future agitation severity scores (r= 0.165, p= 0.009). The temporal lobe WMH (r=0.169, p=0.008) and frontal lobe WMH (r=0.153, p=0.016) contributed most to this this change.ConclusionIrritability and agitation are common NPS and very distressful to patients and caregivers. Our findings of an increase in irritability severity over time as well as higher agitation severity scores at follow-up in participants with MCI-AD and AD with increased WMH loads have important implications for treatment, arguing for aggressive treatment of vascular risk factors in patients with MCI-AD and AD.