Neuropsychiatric correlates of cerebral amyloid burden in a memory clinic sample

Abstract

AbstractBackgroundNeuropsychiatric symptoms (NPS) affect quality of life for both patients and caregivers, worsen cognitive and functional impairment in elderly, and are associated with the development of dementia. Manifestations of neurodegenerative and vascular pathologies including abnormal amyloid deposition and cerebrovascular disease (CeVD) often co‐exist in both cognitively normal and impaired elderly. However, the impact of co‐occurrence of amyloid and CeVD on major clinical outcomes, such as neurocognition and neuropsychiatric disorders, have not been extensively explored. Hence, the present study aimed to determine the neuropsychiatric correlates of cerebral amyloid burden amongst patients across a spectrum of cognitive impairment, adjusting for significant CeVD. We hypothesized that amyloid burden is independently associated with NPS severity.MethodParticipants with or without cognitive impairment from the memory clinic underwent [11C]PiB‐PET and MRI scans between April 2016 and September 2018. NPS were assessed using the 12‐item neuropsychiatric inventory. CeVD markers (cortical infarcts, stenosis, white matter hyperintensities, lacunes, and microbleeds) were graded and significant CeVD was defined following previously validated criteria. The association of NPS severity with global standardized uptake value ratio (SUVR) was analyzed using generalized linear models, controlling for demographics, diagnosis, cognitive function, depression status, and significant CeVD. Possible interactions between amyloid and CeVD were evaluated. The correlations between NPS subsyndromes and regional amyloid uptake were also explored. Holm‐Bonferroni correction was applied to adjust for multiple comparisons.ResultsData for 168 participants [age=75.6 (7.3); female=93 (55.4%); MMSE=22.3 (5.7)] were analyzed, including 24 cognitively normal, 89 MCI, and 55 with dementia. Global SUVR was associated with higher total NPS score [β (CI)=0.67 (0.15‐1.18), p=0.011], driven by hyperactivity subsyndrome [β (CI)=0.96 (0.15‐1.11), p=0.002] and apathy subsyndrome [β (CI)=0.90 (0.34‐1.45), p=0.002]. Apathy subsyndrome was positively correlated with amyloid uptake in the thalamus (r=0.25, p=0.002) and parietal region (r=0.224, p=0.002). There was no significant interaction between global SUVR and significant CeVD on NPS.ConclusionNeuropsychiatric manifestations reflect underlying neurodegenerative pathology independent of vascular burden, suggesting that amyloid and CeVD may exert their effects through different pathways. This finding contributes to the neuropathological understanding of neuropsychiatric disorders, thus informs future development of novel treatment and monitoring of disease progression.