Neuropsychiatric Symptoms of Alzheimer Disease, Parkinson Disease and Lewy Body Dementia: Genetic, Clinical and Therapeutic Overlaps

Background: Parkinson Disease (PD) as well as other parkinsonisms such as Lewy Body Dementia (DLB), are often associated with neuropsychiatric symptoms. Hallucinations, apathy, dysphoria, anxiety, and aberrant motor behaviors are common neuropsychiatric features of both PD and DLB. The overlapping between Alzheimer disease (AD), PD, and DLB seems to be genetic, biological, clinical, and pharmacological. Methods: In this review, a literature search was carried out to analyze the correlation between genetic, molecular, neurophysiological aspects, and neuropsychiatric symptoms of the above-mentioned diseases. Results: Apolipoprotein E-4 (APOE-4), serotonin transporter gene (SLC6A4), and single nucleotide polymorphisms (SNPs) of glucocerebrosidase (GBA) are some of the main altered genes in AD, PDD and DLB. From a molecular point of view, α-synuclein and β/τ-amyloid are the main-altered proteins whose alteration has been implicated in neuropsychiatric symptoms of the diseases, while the entorhinal and parahippocampal regions, medial temporal lobes, limbic regions, and brain stem are the main impaired cerebral regions. Electrophysiological studies provided some insights into the prevalence of neuropsychiatric alterations, including visual hallucinations and poorer cognitive performance, especially in DLB, and pointed out an hypometabolism in frontal, parietal, and temporal lobes in AD. Conclusions: Overall, AD, PD, and DLB may share clinical, neurochemical, and morphological characteristics, thus leading some authors to conceive a Lewy body disease spectrum. Further studies are warranted to find out clinical and neuropathological elements helping differential diagnosis between AD, PD dementia (PDD) and DLB.