Impact of hyperactive neuropsychiatric symptoms on brain morphology in mild cognitive impairment and Alzheimer's disease

BackgroundThe neuroanatomy of hyperactive neuropsychiatric symptoms (NPS) is poorly understood, and it is unclear whether these symptoms result from the same pathogenic processes responsible for cognitive decline or if they have an independent etiology to the neurodegeneration due to Alzheimers disease (AD). ObjectiveWe aim to investigate how the severity of hyperactive NPS (i.e., agitation, disinhibition, and irritability) can impact brain structures at different stages of cognitive decline. MethodsNeuropsychiatric and 3T MRI data from 223 cognitively normal (CN) participants, 367 participants with mild cognitive impairment (MCI) and 175 participants with AD were extracted from the Alzheimer Disease Neuroimaging Initiative (ADNI) database. Statistical analyses based on the general linear model (GLM) were performed to define the effects of neuropsychiatric variables on brain structures in a two-by-two comparison (AD-MCI, CN-MCI and CN-AD). Linear regression analysis was also performed to investigate cortical changes as a function of NPS severity. ResultsIn the AD group, the frontal dorsolateral is the most influenced region receiving an impact from more severe agitation, disinhibition and irritability. In AD, agitation and irritability influence some temporal inferior and parietal superior regions. Furthermore, severe disinhibition seems to have a stronger influence on CN participants compared to the other two groups, particularly in the occipital lingual, frontal middle rostral and frontal pars triangularis regions. ConclusionOur study shows that hyperactive NPS influence differently the brain morphology at different stages of cognitive performance. This might imply that their severity should be evaluated in relation to results of cognitive evaluations.