Behavioral and Psychological Symptoms of Dementia (BPSD): Clinical Characterization and Genetic Correlates in an Italian Alzheimer’s Disease Cohort

Abstract

Background: The occurrence of Behavioral and Psychological Symptoms of Dementia (BPSD) in Alzheimer’s Disease (AD) patients hampers the clinical management and exacerbates the burden for caregivers. The definition of the clinical distribution of BPSD symptoms, and the extent to which symptoms are genetically determined, are still open to debate. Moreover, genetic factors that underline BPSD symptoms still need to be identified. Purpose. To characterize our Italian AD cohort according to specific BPSD symptoms as well as to endophenotypes. To evaluate the associations between the considered BPSD traits and COMT, MTHFR, and APOE genetic variants. Methods. AD patients (n = 362) underwent neuropsychological examination and genotyping. BPSD were assessed with the Neuropsychiatric Inventory scale. Results. APOE and MTHFR variants were significantly associated with specific single BPSD symptoms. Furthermore, “Psychosis” and “Hyperactivity” resulted in the most severe endophenotypes, with APOE and MTHFR implicated as both single risk factors and “genexgene” interactions. Conclusions. We strongly suggest the combined use of both BPSD single symptoms/endophenotypes and the “genexgene” interactions as valid strategies for expanding the knowledge about the BPSD aetiopathogenetic mechanisms.

Personalizing the Care and Treatment of Alzheimer’s Disease: An Overview

“…Besides memory and learning impairments, as well as other cognitive disturbances, 84 AD patients also show “non-cognitive” symptoms, known as behavioral and psychological symptoms of dementia (BPSD). BPSD are heterogeneous group of behaviors, psychiatric symptoms and mood disorders, 85 diagnosed in approximately 90% of AD patients.…”

“…BPSD are heterogeneous group of behaviors, psychiatric symptoms and mood disorders, 85 diagnosed in approximately 90% of AD patients. BPSD encompass symptoms such as sleep disturbances, anxiety, aggression, depression, wandering, delusion, hallucinations, and disinhibition, 84–87 which are clustered as 1) apathy; 2) affective (anxiety, depression); 3) psychosis (paranoia, delusions, hallucinations); and 4) disinhibition (motor hyperactivity, impulsivity, aggression). 84 , 86 More than 50% of AD patients show more than four neuropsychiatric symptoms at the same time.…”

“…BPSD encompass symptoms such as sleep disturbances, anxiety, aggression, depression, wandering, delusion, hallucinations, and disinhibition, 84–87 which are clustered as 1) apathy; 2) affective (anxiety, depression); 3) psychosis (paranoia, delusions, hallucinations); and 4) disinhibition (motor hyperactivity, impulsivity, aggression). 84 , 86 More than 50% of AD patients show more than four neuropsychiatric symptoms at the same time. Therefore, the presence of such symptoms affects normal functioning, as well as further cognitive decline, 88 and represents one of the main reasons for the institutionalization of AD patients.…”

Integrative Base Ontology for the Research Analysis of Alzheimer’s Disease-Related Mild Cognitive Impairment

“…Psychological testing and NT lack these problems while maintaining comparable reliability to biomarkers testing (Klages et al, 2005 ; García-Herranz et al, 2020 ). Psychological testing focuses on detecting depressions, anxiety, apathy, and other behavioral and psychological symptoms of dementia (Scassellati et al, 2020 ), while neuropsychological testing is capable of measuring cognitive domains, such as memory, executive function, or attention (Hastings et al, 2014 ), and detecting their alterations. Both psychological and neuropsychological testing should be considered when assessing a subject’s cognitive status because behavioral changes can influence NT scores (García-Herranz et al, 2020 ; Wasserman et al, 2020 ).…”

Biomarkers for Alzheimer’s Disease: Where Do We Stand and Where Are We Going?

“…Therefore, understanding the molecular mechanisms of this interaction could allow the development of new personalized therapeutic approaches for treating AD [ 13 ]. Focusing on the occurrence of behavioral and psychological symptoms of dementia in AD (BPSD), other authors have found an interesting association between APOE and MTHFR genetic variants and BPSD, expanding the knowledge about the BPSD etiopathogenetic mechanisms, which in turn, leads not only improve the clinical/diagnostic assessment, but also to better definite suitable treatments [ 14 ].…”