Title:Neuropsychiatric Disturbances in Alzheimer’s Disease: What Have We Learned from Neuropathological Studies?
Volume: 13
Issue: 10
Author(s): Debby Van Dam, Yannick Vermeiren, Alain D. Dekker, Petrus J.W. Naudé and Peter P. De Deyn
Affiliation:
Keywords:
Aggression, amyloid, depression, neurofibrillary tangles, neuronal loss, psychosis, neurotransmitter.
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.