title: Neuropsychiatric Disturbances in Alzheimer's Disease: What Have We Learned from Neuropathological Studies?
abstract: Neuropsychiatric symptoms (NPS) are an integral part of the dementia syndrome and were therefore recently included in the core diagnostic criteria of dementia. The near universal prevalence of NPS in Alzheimer's disease (AD), combined with their disabling effects on patients and caregivers, is contrasted by the fact that few effective and safe treatments exist, which is in part to be attributed to our incomplete understanding of the neurobiology of NPS. In this review, we describe the pathological alterations typical for AD, including spreading and evolution of burden, effect on the molecular and cellular integrity, functional consequences and atrophy of NPS-relevant brain regions and circuits in correlation with specific NPS assessments. It is thereby clearly established that NPS are fundamental expressions of the underlying neurodegenerative brain disease and not simply reflect the patients' secondary response to their illness. Neuropathological studies, moreover, include a majority of end-stage patient samples, which may not correctly represent the pathophysiological environment responsible for particular NPS that may already be present in an early stage, or even prior to AD diagnosis. The burdensome nature and high prevalence of NPS, in combination with the absence of effective and safe pharmacotherapies, provide a strong incentive to continue neuropathological and neurochemical, as well as imaging and other relevant approaches to further improve our apprehension of the neurobiology of NPS.
authors.forename: Debby
authors.initials: D
authors.lastname: Van Dam
authors.forename: Yannick
authors.initials: Y
authors.lastname: Vermeiren
authors.forename: Alain D
authors.initials: AD
authors.lastname: Dekker
authors.forename: Petrus J W
authors.initials: PJ
authors.lastname: Naudé
authors.affiliation: Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, Department of Biomedical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, and, Faculty of Medical and Health Care Sciences, University of Antwerp, Universiteitsplein 1, BE-2610 Wilrijk (Antwerp), Belgium.
authors.forename: Peter P De
authors.initials: PP
authors.lastname: Deyn
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000473:pathology*; D001526:Behavioral Symptoms / Q000209:etiology* / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D017028:Caregivers / Q000523:psychology; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology; D004660:Encephalitis / Q000209:etiology; D006801:Humans