Neuropsychiatric Symptoms In Older Adults Research Articles

Salience network segregation mediates the effect of tau pathology on mild behavioral impairment.

A recently developed mild behavioral impairment (MBI) diagnostic framework standardizes the early characterization of neuropsychiatric symptoms in older adults. However, the joint contributions of Alzheimer's disease (AD) pathology and brain function to MBI remain unclear. We test a novel model assessing direct relationships between AD biomarker status and MBI symptoms, as well as mediated effects through segregation of the salience and default-mode networks, using data from 128 participants with diagnosis of amnestic mild cognitive impairment or mild dementia-AD type. We identified a mediated effect of tau positivity on MBI through functional segregation of the salience network from the other high-level, association networks. There were no direct effects of AD biomarkers status on MBI. Our findings suggest that tau pathology contributes to MBI primarily by disrupting salience network function and emphasize the role of the salience network in mediating relationships between neuropathological changes and behavioral manifestations. Network segregation mediates Alzheimer's disease (AD) pathology impact on mild behavioral impairment (MBI). The salience network is pivotal in linking tau pathology and MBI. This study used path analysis with AD biomarkers and network integrity. The study evaluated the roles of salience, default mode, and frontoparietal networks. This is the first study to integrate MBI with AD biomarkers and network functionality.

Pimavanserin's Safety Profile: Insights from a Phase 3b Clinical Trial.

The recent Alva et al. Phase 3b study on pimavanserin use in older adults with neurodegenerative diseases (NDDs), specifically including Alzheimer's disease, vascular dementia, Parkinson's disease (with or without dementia), frontotemporal dementia, and dementia with Lewy bodies, provides important new data on its safety for managing neuropsychiatric symptoms in this population. This commentary on the study further examines the findings within the broader context of antipsychotic therapy as it has evolved from chlorpromazine to pimavanserin in a continuous search for greater safety. Comparing pimavanserin's safety and efficacy profile with historical data and regulatory milestones provides a nuanced perspective for clinicians regarding the significance of the drug's known advantages over prior antipsychotic treatments. More research is needed to determine the full potential of pimavanserin to improve neuropsychiatric symptoms in older adults with NDDs.

Salience Network Segregation Mediates the Effect of Tau Pathology on Mild Behavioral Impairment.

A recently developed mild behavioral impairment (MBI) diagnostic framework standardizes the early characterization of neuropsychiatric symptoms in older adults. However, the links between MBI, brain function, and Alzheimer's disease (AD) biomarkers are unclear. Using data from 128 participants with diagnosis of amnestic mild cognitive impairment and mild dementia - Alzheimer's type, we test a novel model assessing direct relationships between AD biomarker status and MBI symptoms, as well as mediated effects through segregation of the salience and default-mode networks. We identified a mediated effect of tau positivity on MBI through functional segregation of the salience network from the other high-level, association networks. There were no direct effects of AD biomarkers status on MBI. Our findings suggest an indirect role of tau pathology in MBI through brain network dysfunction and emphasize the role of the salience network in mediating relationships between neuropathological changes and behavioral manifestations.

Neuropsychiatric Profiles and Cerebral Amyloid Burden in Adults without Dementia

Plain Language SummaryThis study examines how patients’ and their caregivers’ report of neuropsychiatric symptoms are associated with amyloid burden, of the primary markers of risk for amyloid burden, in older adults without dementia. Amyloid burden was measured using a PET-CT scan, and neuropsychological symptoms were measured with a self-reported and an informant-reported questionnaire. We found that neuropsychiatric symptoms were associated with amyloid burden in older adults without dementia, and these relationships were stronger in older adults with greater cognitive and functional impairment. In particular, caregivers’ report of anxiety, depression, and irritability and patients’ report of cognitive concerns were associated with greater amyloid burden. Neuropsychiatric symptoms, observed by both the patient and the informant, may be promising first identifiers of the neuropathology associated with Alzheimer’s disease and related dementias. Although neuropsychiatric symptoms have been characterized in persons with dementia, we do not yet have a clear understanding of how neuropsychiatric symptoms appear in non-dementia stages or which instruments may be the most sensitive screening tools for neuropsychiatric symptoms in older adults without dementia. These older adults without dementia may exist in a window of opportunity for behavioral and pharmacologic interventions that may prevent or slow clinical progression.

Neuropsychiatric symptoms and ApoE genotype in older adults without dementia: a cross-sectional study.

The ApoE genotype and neuropsychiatric symptoms (NPS) are known risk factors for cognitive decline in older adults. However, the interaction between these variables is still unclear. The aim of this study was to determine the association between the presence of the ApoE ε4 allele and the occurrence of NPS in older adults without dementia. In this cross-sectional investigation we determined the apolipoprotein E (ApoE) genotype of 74 older adults who were either cognitively normal (20.3% / Clinician Dementia Rating Scale (CDR): 0) or had mild cognitive impairment (MCI: 79.7% / CDR: 0.5). We used a comprehensive cognitive assessment protocol, and NPS were estimated by the Neuropsychiatric Inventory-Clinician Rating Scale (NPI-C), Mild Behavioural Impairment-Checklist (MBI-C), Hamilton Rating Scale for Depression (HAM-D), and Apathy Inventory. ApoE ε4 carriers had higher MBI-C total scores than ApoE ε4 noncarriers. Correlations between NPS and ApoE genotype were observed for two NPI-C domains, although in opposite directions: the ApoE ε4 allele was associated with a 1.8 unit decrease in the estimated aberrant motor disturbance score and with a 1.3 unit increase in the estimated appetite/eating disorders score. All fitted models were significant, except for the one fitted for the domain delusions from the NPI-C. Among individuals with amnestic MCI, ε4 carriers presented higher depression score (HAM-D) than noncarriers; in turn, ε4 noncarriers exhibited higher aggression score (NPI-C) than ε4 carriers. Our analyses showed associations between NPS and the presence of the ApoE ε4 allele in two NPI-C domains, despite the sample size. Furthermore, compared to noncarriers, the presence of the ApoE ε4 correlated positively with appetite/eating disorders and negatively with aberrant motor disturbance domain. Examination of the amnestic MCI group displayed significant, although weak, associations. Therefore, ε4 carriers exhibited higher depression scores according to the HAM-D scale compared to ε4 noncarriers. Conversely, ε4 noncarriers had higher scores in the aggression domain of the NPI-C than ε4 carriers.

Mild behavioral impairment as an indicator of early dementia neurodegeneration: Evidence from structural neuroimaging

AbstractBackgroundMild behavioral impairment (MBI) refers to the de novo emergence of persistent neuropsychiatric symptoms in older adults and has been associated with cognitive decline and incident dementia. The purpose of this study was to identify the structural neural correlates of MBI using a hypothesis‐driven region‐of‐interest (ROI) approach.MethodThe study cohort consisted of 744 participants (60.3% female; mean and SD of age = 71.0 ± 9.7 years; mean and SD of education: 15.8 ± 5.3 years) without dementia from the National Alzheimer’s Coordinating Centre dataset. Structural T1‐weighted images for each participant were processed and segmented using FreeSurfer and then normalized by age, sex, intracranial volume, scanner characteristics, and image quality to generate adjusted measures of grey matter volume (GMV) for each ROI. Our primary ROIs included five regions, each representing one Braak stage: entorhinal cortex (stage I), hippocampus (stage II), fusiform gyrus (stage III), inferior temporal cortex (stage IV), and frontal pole (stage V). We also included three hippocampal subfields (CA1, CA3, CA4) and four ROIs commonly associated with various psychiatric disorders (amygdala, insula, anterior cingulate, prefrontal cortex) as a secondary analysis. All ROIs are anatomically highlighted in Figure 1. Participants were classified as MBI+ if they presented with MBI symptoms derived from the Neuropsychiatric Inventory Questionnaire for two consecutive visits one year apart. Logistic regressions adjusting for cognitive diagnosis (cognitively normal, n = 568; mild cognitive impairment, n = 176) were used to model the relationship between ROI GMV (predictor) and MBI status (outcome).ResultAs shown in Table 1, lower GMV in early Braak stage ROIs (entorhinal cortex and hippocampus) was associated with MBI+ status. This trend was maintained for all hippocampal subfield ROIs. However, mid‐late Braak stage ROI (fusiform gyrus, inferior temporal cortex, frontal pole) GMVs were not associated with MBI status. For psychiatric disorder ROIs, lower GMV in only the amygdala was associated with MBI+ status.ConclusionOur findings demonstrate that the presence of MBI may implicate neurodegeneration in regions linked to early‐stage dementia. Furthermore, this explicitly identifies MBI as a neurodegenerative marker sharing few neuroanatomical correlates with psychiatric disorders, despite their clinical manifestations.aging after age 90.

Does anticholinergic burden predict cognitive decline or neuropsychiatric symptoms in older adults with mild cognitive impairment or dementia?

Does anticholinergic burden predict cognitive decline or neuropsychiatric symptoms in older adults with mild cognitive impairment or dementia?

Anticholinergic burden for prediction of cognitive decline or neuropsychiatric symptoms in older adults with mild cognitive impairment or dementia.

Medications with anticholinergic properties are commonly prescribed to older adults with a pre-existing diagnosis of dementia or cognitive impairment. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden because of its potential to cause adverse effects. It is possible that a high anticholinergic burden may be a risk factor for further cognitive decline or neuropsychiatric disturbances in people with dementia. Neuropsychiatric disturbances are the most frequent complication of dementia that require hospitalisation, accounting for almost half of admissions; hence, identification of modifiable prognostic factors for these outcomes is crucial. There are various scales available to measure anticholinergic burden but agreement between them is often poor. Our primary objective was to assess whether anticholinergic burden, as defined at the level of each individual scale, was a prognostic factor for further cognitive decline or neuropsychiatric disturbances in older adults with pre-existing diagnoses of dementia or cognitive impairment. Our secondary objective was to investigate whether anticholinergic burden was a prognostic factor for other adverse clinical outcomes, including mortality, impaired physical function, and institutionalisation. We searched these databases from inception to 29 November 2021: MEDLINE OvidSP, Embase OvidSP, PsycINFO OvidSP, CINAHL EBSCOhost, and ISI Web of Science Core Collection on ISI Web of Science. We included prospective and retrospective longitudinal cohort and case-control observational studies, with a minimum of one-month follow-up, which examined the association between an anticholinergic burden measurement scale and the above stated adverse clinical outcomes, in older adults with pre-existing diagnoses of dementia or cognitive impairment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, and undertook data extraction, risk of bias assessment, and GRADE assessment. We summarised risk associations between anticholinergic burden and all clinical outcomes in a narrative fashion. We also evaluated the risk association between anticholinergic burden and mortality using a random-effects meta-analysis. We established adjusted pooled rates for the anticholinergic cognitive burden (ACB) scale; then, as an exploratory analysis, established pooled rates on the prespecified association across scales. MAIN RESULTS: We identified 18 studies that met our inclusion criteria (102,684 older adults). Anticholinergic burden was measured using five distinct measurement scales: 12 studies used the ACB scale; 3 studies used the Anticholinergic Risk Scale (ARS); 1 study used the Anticholinergic Drug Scale (ADS); 1 study used the Anticholinergic Effect on Cognition (AEC) Scale; and 2 studies used a list developed by Tune and Egeli. Risk associations between anticholinergic burden and adverse clinical outcomes were highly heterogenous. Four out of 10 (40%) studies reported a significantly increased risk ofgreater long-term cognitive decline for participants with an anticholinergic burden compared to participants with no or minimal anticholinergic burden. No studies investigated neuropsychiatric disturbance outcomes. One out of four studies (25%) reported a significant association with reduced physical function for participants with an anticholinergic burden versus participants with no or minimal anticholinergic burden. No study (out of one investigating study) reported a significant association between anticholinergic burden and risk of institutionalisation. Six out of 10 studies (60%) found a significantly increased risk of mortality for those with an anticholinergic burden compared to those with no or minimal anticholinergic burden. Pooled analysis of adjusted mortality hazard ratios (HR) measured anticholinergic burden with the ACB scale, and suggested a significantly increased risk of death for those with a high ACB score relative to those with no or minimal ACB scores (HR 1.153, 95% confidence interval (CI) 1.030 to 1.292; 4 studies, 48,663 participants). An exploratory pooled analysis of adjusted mortality HRs across anticholinergic burden scales also suggested a significantly increased risk of death for those with a high anticholinergic burden (HR 1.102, 95% CI 1.044 to 1.163; 6 studies, 68,381 participants). Overall GRADE evaluation of results found low- or very low-certainty evidence for all outcomes. AUTHORS' CONCLUSIONS: There is low-certainty evidence that older adults with dementia or cognitive impairment who have a significant anticholinergic burden may be at increased risk of death. No firm conclusions can be drawn for risk of accelerated cognitive decline, neuropsychiatric disturbances, decline in physical function, or institutionalisation.

The Association Between Somatic Symptom Disorders and Neurocognitive Disorders: A Systematic Review

Onset of neuropsychiatric symptoms in older adults may represent prodromal manifestations of neurodegenerative disorders. The association between the onset of somatic symptom and related disorders (SSRD) and the subsequent development of neurodegenerative disorders remains unclear. A critical review of studies describing the association between SSRD and neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, and Lewy body dementia was performed. To critically review studies describing the association between SSRD and neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, and Lewy body dementia. A systematic review of Web of Science Core databases was carried out from inception of databases up to May 2021 to identify observational studies pertaining to both SSRD and neurodegenerative disorders. Data was extracted and compiled regarding subjects enrolled, age at onset of the SSRD and at onset of the neurodegenerative disorders, and specific SSRD manifestations and underlying neuropathologies reported. Thirteen articles were included. Of the 123 identified subjects with SSRD at baseline, 34.1% developed a neurodegenerative disorder, with 80.9% of these being a Lewy body spectrum disorder. The interval between onset of SSRD manifestations and subsequent development of a neurodegenerative disorder was less than 3 years for half of the cases. Of the 1,494 subjects with a neurodegenerative disorder at baseline retrieved, SSRD manifestations were reported in 33.4% of Lewy body spectrum disorders cases. Onset of SSRD manifestations antedated or was concomitant to the diagnosis of the Lewy body spectrum disorder in 65.6% of cases. While limited, current evidence suggests a possible association between late-onset SSRD and the subsequent development of neurodegenerative disorders, notably Lewy body spectrum disorders.

Effects of intermittent theta burst stimulation (iTBS) on executive function and neuropsychiatric symptoms in older adults with mild to moderate dementia due to Alzheimer's disease: Preliminary findings of a randomized double‐blind clinical trial

AbstractBackgroundStudies on brain networks indicate that the functional integration between brain networks decreases progressively with Alzheimer`s disease (AD). The intermittent Theta Burst Stimulation (ITBS) has been shown to modulate the connectivity of DMN administered to parietal (PPC) and dorsolateral prefrontal (DLPFC) cortex.MethodWe selected 9 patients with AD, and a randomized double‐blind clinical trial was performed comparing the active iTBS (n=5) with sham group (n=4)of older adults with mild to moderate AD. Active iTBS condition were submitted to 21 iTBS sessions on the right and left DLPFC and the right and left PPC. All participants were assessed at baseline, week 3,week 6, 3 and 6 months. Executive functions were assessed by validated and standardized tests for this population. Behavioral symptoms were evaluated by Neuropsychiatric Inventory (NPI). The changes in performance between assessments were compared using the reliable change index (RCI).ResultOn phonemic verbal fluency two participants from intervention group show decline of this ability. One of them in the 3rd week (RCI = ‐2.16) and in the 6th week (RCI = ‐3.24). And another only in the 6th week (RCI = ‐3.24). After this period, the performance was similar to that of the baseline for both. Despite this, there were three patients who showed change in phonemic verbal fluency in the third week. One participant from sham group also showed improvement in the sixth week (RCI = 2.16).Regarding working memory, a sham participant showed decline in this ability after the sixth week assessment (RCI = ‐7.38) and this performance remained below that presented in the baseline until the sixth month. And another from intervention group showed improvement in the third week (RCI = 2.46), but from the sixth week on, the performance returned to the same level as the baseline.ConclusionThe improvement and impairment of cognitive variables in comparison to baseline was associated with temporal proximity of neurostimulation procedures for both groups. It is still necessary to expand the sample size to clarify which factors impact on this outcomes.

Self and informant‐rated mild behavioral impairment and genetic risk for AD: The respondent matters

AbstractBackgroundLate‐life onset neuropsychiatric symptoms (NPS) have received increasing attention in recent years because of their prognostic potential for neurodegenerative disease. As focus intensifies, appropriate measurement will be critical. The emergence of Mild Behavioral Impairment ‐ which describes late‐life onset apathy, mood/anxiety symptoms, impulse dyscontrol, social inappropriateness, and psychosis ‐ and the MBI‐Checklist (MBI‐C), developed to capture these symptoms in accordance with the ISTAART‐AA MBI criteria, has been a step forward. Previous work has demonstrated only modest correlation between proxy informant and self‐rated MBI‐C responses, but the significance of these differences in responses is not yet understood. Moreover, there is relatively less work examining non‐affective late‐life NPS. To explore both of these factors, we examined the relationship between genetic risk for Alzheimer’s disease and the five MBI domains in a sample of cognitively normal older adults.MethodGenetic and clinical data from 2,529 cognitively normal participants aged ≥65 in the PROTECT study were analysed. MBI was evaluated using the MBI‐C; individual domain scores were calculated, and participants dichotomised into domain ‘present’ or ‘absent’. Polygenic risk scores (PRS) for Alzheimer’s disease were used as predictors in binary logistic regression models with the MBI domains, each rated by self and by proxy, as separate outcomes. To evaluate whether AD PRS was associated with depression, the most commonly considered NPS in older adults, we also tested the association between AD PRS and PHQ‐9 score (>=5 or <5).ResultAD PRS was associated with a greater risk of apathy and impulse dyscontrol in proxy MBI‐C ratings but not in self‐report MBI‐C ratings (OR: 1.2 [95% CI: 1.06‐1.40], p=0.004; OR: 1.12 [95% CI: 1.01‐1.24], p=0.03, respectively). There was no association between AD PRS and PHQ‐9 symptoms.ConclusionProxy informant and self‐reported MBI‐C elicit different associations in analysis of AD genetic risk. These findings suggest that even in cognitively normal older adults, proxy informant ratings are important to consider in the evaluation of NPS and risk of dementia. There was no association between PHQ‐9 symptoms and AD PRS, highlighting the importance of the multi‐domain MBI‐C as a specific tool to capture late‐life NPS as risk factors for dementia.

Anticholinergic burden for prediction of cognitive decline or neuropsychiatric symptoms in older adults with mild cognitive impairment or dementia

Anticholinergic burden for prediction of cognitive decline or neuropsychiatric symptoms in older adults with mild cognitive impairment or dementia

Association Between BDNF Val66Met Polymorphism and Mild Behavioral Impairment in Patients With Parkinson's Disease.

Neuropsychiatric symptoms (NPS) are common in Parkinson's disease (PD) and have demonstrated an association with the p. Val66Met, a polymorphism in the BDNF gene. Mild behavioral impairment (MBI) is a validated syndrome describing emergent and persistent NPS in older adults as a marker of potential cognitive decline and dementia. This study investigated if PD patients with the Met allele were more likely to have MBI and whether they had impairments in specific domains of MBI using the Mild Behavioral Impairment Checklist (MBI-C) as the MBI ascertainment tool. One hundred forty-six PD patients were screened for neuropsychiatric and cognitive impairments with the MBI-C and the Montreal Cognitive Assessment (MoCA). All participants were genotyped for the BDNF p.Val66Met single-nucleotide polymorphism (SNP) using TaqMan Genotyping Assay. Statistical analysis was performed using multiple linear and logistic regression models. Met carriers had a 2 times higher likelihood of being MBI positive (MBI-C total score ≥8) than Val carriers. Met carriers had significantly higher MBI-C total scores and significantly greater impairments in the mood/anxiety and the psychotic domains of MBI-C compared to Val carriers. These findings indicate that the BDNF Met allele is associated with a higher neuropsychiatric burden in PD.

Neuropsychiatric symptoms associated with family caregiver burden and depression.

ABSTRACTAlzheimer's disease (AD) is a progressive and degenerative condition affecting several cognitive areas, with a decline in functional abilities and behavioral changes.Objective:To investigate the association between neuropsychiatric symptoms in older adults with AD and caregiver burden and depression.Methods:A total of 134 family caregivers of older people diagnosed with AD answered a questionnaire with sociodemographic data and questions concerning the care context, neuropsychiatric symptoms, caregiver burden, and depressive symptoms.Results:Results revealed that 95% of older adults had at least one neuropsychiatric symptom, with the most common being: apathy, anxiety, and depression. Among the 12 neuropsychiatric symptoms investigated, 10 were significantly associated with caregiver burden, while 8 showed significant correlations with depressive symptoms.Conclusions:Neuropsychiatric symptoms were related to caregiver burden and depressive symptoms. In addition to the older adult with AD, the caregiver should receive care and guidance from the health team to continue performing quality work.

ApoE ε4 status in pre‐dementia risk states, mild behavioural impairment and subjective cognitive decline, and the risk of incident cognitive decline

AbstractBackgroundDementia has an increasing global burden with over 40 million affected individuals. With sub‐optimal advances in drug development, there is an increasing shift to determine risk of dementia in the non‐demented population. Assessment of neuropsychiatric symptoms (NPS) may offer an opportunity to capture the at‐risk group earlier. Mild Behavioural Impairment (MBI) is a validated neurobehavioural syndrome, characterized by the emergence of sustained NPS in older adults as an at‐risk state for dementia. Cognitively, subjective cognitive decline (SCD) is a dementia at‐risk group in which cognitive symptoms are reported in the absence of objective findings. The apolipoprotein epsilon 4 (ApoE ε4) gene is a well‐known risk marker for dementia. We aim to determine the frequency of ApoE homozygosity in SCD, stratified by MBI status cross‐sectionally, and calculate the hazard of incident cognitive decline in this group longitudinally.MethodData from 5005 participants in the National Alzheimer’s Coordinating Center (NACC) were used to capture older adults who were cognitively normal, but had subjective cognitive complaints (SCD). We determined MBI status (+/‐) using a previously published transformation algorithm of NPI‐Q scores. We tabulated ApoE genotype in both groups. We compared proportion of ApoE homozygousity (APOE ε4+/+)in the MBI+ versus the MBI‐ group. Additionally, a Cox proportional hazards regression will be done to capture hazard of incident mild cognitive impairment in MBI+ versus MBI‐.ResultA two‐sample test of proportions of MBI+/‐ status stratified by ApoE ε4+/+resulted in significant differences between groups with homozygosity more frequent in MBI+ versus MBI‐ (p<0.001). We will also present the results of the Cox proportional hazards regression analysis.ConclusionIn older adults with subjective cognitive decline, ApoE ε4 allele homozygosity was more frequently seen in the MBI+ group. These findings provide additional evidence for the utility in determining MBI status in SCD.

The Impact of COVID-19 Infection and Enforced Prolonged Social Isolation on Neuropsychiatric Symptoms in Older Adults With and Without Dementia: A Review.

Background: The sudden and drastic changes due to the Coronavirus Disease 19 (COVID-19) pandemic have impacted people's physical and mental health. Clinically-vulnerable older people are more susceptible to severe effects either directly by the COVID-19 infection or indirectly due to stringent social isolation measures. Social isolation and loneliness negatively impact mental health in older adults and may predispose to cognitive decline. People with cognitive impairments may also be at high risk of worsening cognitive and mental health due to the current pandemic. This review provides a summary of the recent literature on the consequences of COVID-19, due to either viral infection or social isolation, on neuropsychiatric symptoms in older adults with and without dementia.Methods: A search was conducted in PubMed and Web of Science to identify all relevant papers published up to the 7th July 2020. Two independent assessors screened and selected the papers suitable for inclusion. Additional suitable papers not detected by literature search were manually added.Results: Fifteen articles were included: 8 focussed on the psychiatric symptoms caused by the COVID-19 infection and 7 investigated the impact of social isolation on older adults' neuropsychiatric symptoms. Four studies included older adults without dementia and 11 included patients with cognitive impairment mainly due to Alzheimer's disease. All studies found that different neuropsychiatric symptoms emerged and/or worsened in older adults with and without dementia. These changes were observed as the consequence of both COVID-19 infection and of the enforced prolonged conditions of social isolation. Cases were reported of viral infection manifesting with delirium at onset in the absence of other symptoms. Delirium, agitation and apathy were the symptoms most commonly detected, especially in people with dementia.Conclusion: The available evidence suggests that the COVID-19 pandemic has a wide negative impact on the mental well-being of older adults with and without dementia. Viral infection and the consequent social isolation to limit its spreading have a range of neuropsychiatric consequences. Larger and more robustly designed studies are needed to clarify such effects and to assess the long-term implications for the mental health of older adults, and to test possible mitigating strategies.

Association of Hearing Loss With Neuropsychiatric Symptoms in Older Adults With Cognitive Impairment

This study investigated the association between hearing loss and NPS among community- dwelling patients from a tertiary memory care center. Participants of this cross-sectional study were patients followed at the Johns Hopkins Memory and Alzheimer's Treatment Center who underwent audiometric testing during routine clinical practice between October 2014 and January 2017. Included measures were scores on the Neuropsychiatric Inventory-Questionnaire and the Cornell Scale for Depression in Dementia. Participants (n = 101) were on average 76 years old, mostly female and white, and had a mean Mini-Mental State Examination score of 23. We observed a positive association between audiometric hearing loss and the number of NPS (b = 0.7 per 10 dB; 95% confidence interval [CI]: 0.2, 1.1; t = 2.86; p = 0.01; df = 85), NPS severity (b = 1.3 per 10 dB; 95% CI: 0.4, 2.5; t = 2.13; p = 0.04; df = 80), and depressive symptom severity (b = 1.5 per 10 dB; 95% CI: 0.4, 2.5; t = 2.83; p = 0.01; df = 89) after adjustment for demographic and clinical characteristics. Additionally, the use of hearing aids was inversely associated with the number of NPS (b = -2.09; 95% CI -3.44, -0.75; t = -3.10; p = 0.003; df = 85), NPS severity (b = -3.82; 95% CI -7.19, -0.45; t = -2.26; p = 0.03; df = 80), and depressive symptom severity (b = -2.94; 95% CI: -5.93, 0.06; t = 1.70; p = 0.05; df = 89). Among patients at a memory clinic, increasing severity of hearing loss was associated with a greater number of NPS, more severe NPS, and more severe depressive symptoms, while hearing aid use was associated with fewer NPS, lower severity, and less severe depressive symptoms. Identifying and addressing hearing loss may be a promising, low-risk, non-pharmacological intervention in preventing and treating NPS.

C-10 Interaction of ApoE4 and Gender in Neuropsychiatric Presentation in Probable Alzheimer’s Disease

Abstract Objective Individuals with probable Alzheimer’s disease (pAD) often have neuropsychiatric symptoms; however, the relationship of these symptoms and ApoE4 status is unclear. Recent research suggests gender moderates the relationship of ApoE4 to AD. We examined how ApoE4 genetic status and gender predict neuropsychiatric symptoms in older adults with pAD. Method Data from the National Alzheimer’s Coordinating Centers (NACC) was utilized in the present study. We included only individuals diagnosed with pAD with collaterals who were judged reliable by clinical NACC staff and who saw the participant at least three times per week. The selected sample (N = 6943) was 52% male; 85.6% White, 10.2% African American; and 7.5% Hispanic. Average age was 73 years. The Neuropsychiatric Inventory-Questionnaire, completed by the participant’s collateral, was used to assess symptoms. Analyses controlled for age and cognitive impairment as measured by the Mini-Mental State Examination. Results The presence of at least one ApoE4 allele predicted higher severity of delusions, p = .04. Males had higher severity of agitation, apathy, and irritability; females had higher delusions, depression, and anxiety, all p’s < .05. Gender moderated the relationship of ApoE4 with disinhibition, night disturbances, and appetite, all p’s < .05. In all three cases, for males, scores were higher for non-carriers than for ApoE4 carriers; however, for females, differences did not exist between carriers and non-carriers. Conclusions Differences between ApoE4 carriers and non-carriers as well as between genders are demonstrated, and evidence supports the hypothesis that gender and ApoE4 status interact to predict some pAD neuropsychiatric symptomatology.

Effectiveness of multisensory stimulation in managing neuropsychiatric symptoms in older adults with major neurocognitive disorder: a systematic review

The objective of the review was to synthesize the effectiveness of multisensory stimulation in managing neuropsychiatric symptoms (NPS) in older adults with major neurocognitive disorder (NCD). Major neurocognitive disorder is characterized by changes in specific cognitive domains with a progressive deterioration in cognitive ability and capacity for independent living. Most older adults with this condition have one or more concomitant symptoms known as NPS. Evidence shows that nonpharmacological therapies have been effective in controlling these symptoms, with multisensory stimulation attracting further investigation. The review considered studies on older adults aged 65 years or over with major NCD. The intervention of interest was multisensory stimulation, and the comparator was usual care (e.g. no occupational therapy, no cognitive training, and no art therapy, but with possible control of activities such as looking at photographs or doing quizzes), or another intervention (e.g. occupational therapy, cognitive training and art therapy). Primary outcomes were NPS (agitation, aggression, motor disturbances, mood liability, anxiety, apathy, night-time behaviour, eating disorders, delusion and hallucination). Secondary outcomes were quality of life, functional status in activities of daily living, cognitive status and caregiver burden. Experimental study designs were considered. A broad range of keywords and a three-step search strategy were used to identify potentially eligible published and unpublished studies from January 1990 to June 2016 in major healthcare-related online databases. Studies in English, Spanish and Portuguese were included. Two independent reviewers assessed the methodological quality of eight included studies using the Joanna Briggs Institute (JBI) Critical Appraisal Checklists for Randomized Controlled Trials and Quasi-Experimental Studies. Data were extracted using the standardized data extraction tool from the JBI System for the Unified Management, Assessment and Review of Information (JBI SUMARI) and included details about the interventions, populations, study methods and outcomes of interest. Significant differences were found between participants, interventions, outcome measures (clinical heterogeneity), and designs (methodological heterogeneity). For these reasons, a meta-analysis could not be performed. Therefore, the results have been described in a narrative format. Eight studies (seven randomized controlled trials and one quasi-experimental study) were included, with a total sample of 238 participants (pre-intervention). Four studies confirmed the effectiveness of multisensory stimulation in domains such as physically nonaggressive behavior, verbally agitated behavior and agitation. However, these effects did not always persist in the long-term. Six studies showed poorly consistent results on the effects of multisensory stimulation in improving mood, with only one displaying significant effects. Similarly, despite poor results, two studies showed benefits concerning anxiety. Participants reported significantly decreased levels of anxiety over the course of the intervention, and this improvement persisted in the long-term. In regard to functional status in activities of daily living, two studies reported an improvement in the short-term. Moreover, the effectiveness in cognitive domains such as memory and attention to surroundings also showed inconsistent results across the seven studies that analyzed this outcome. Two studies reflected an improvement during the intervention, but also reported a gradual decline in the long-term. Only one study observed significantly better results during the intervention that persisted until the follow-up assessment. Apathy, night-time behavior, eating disorders, delusion and hallucination were NPS that were not explored in the studies that met the criteria to be included in this review. These findings suggest that multisensory stimulation could be an effective intervention for managing NPS in older adults with major NCD in a mild to severe stage, particularly for managing behavioral symptoms such as agitation. This research provides an indication of the likely effect of the multisensory stimulation on NPS such as agitation and anxiety, as well on cognitive status.

Path analysis of caregiver characteristics and neuropsychiatric symptoms in Alzheimer's disease patients.

To determine the direct and indirect relationships of sociodemographic, emotional and behavioral characteristics of family caregivers of Alzheimer's disease patients who have neuropsychiatric symptoms. A total of 134 family caregivers answered a questionnaire with sociodemographic data, and questions regarding the context of care, Neuropsychiatric Inventory, Zarit Burden Interview, Dementia Management Strategies Scale and the Beck Depression Inventory. A path analysis was used to model the direct and indirect relationships among the selected variables. Being a female caregiver, presenting high levels of burden, a moderate degree of depressive symptoms, distress (Neuropsychiatric Inventory total distress score), active management strategies and criticism management strategies were significantly associated with the total score of neuropsychiatric symptoms. The caregiver burden and use of criticism management strategies were directly related to neuropsychiatric symptoms in older adults with Alzheimer's disease. The use of active management strategies and depressive symptoms of caregivers had indirect relationships with neuropsychiatric symptoms through caregiver burden. Overburdened caregivers and the use of dysfunctional management strategies are associated with a greater presence of neuropsychiatric symptoms in Alzheimer's disease patients. These aspects should be considered when developing interventions for caregivers to manage neuropsychiatric symptoms and overall treatment of patients with dementia. Geriatr Gerontol Int 2018; 18: 1177-1182.