Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment, cerebrovascular disease and Parkinson disease: A cross sectional and longitudinal study.

OBJECTIVES: Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses. METHODS: The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2-years follow-up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal-executive circuits. RESULTS: Cross-sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal-executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal-executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal-executive circuits, respectively. CONCLUSIONS: The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross-sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.

Neuropsychiatric features in a multi-ethnic population with Alzheimer disease and mild cognitive impairment.

BACKGROUND: Alzheimer disease (AD) is more prevalent in African American (AA) and Hispanic White (HIW) compared to Non-Hispanic White (NHW) individuals. Similarly, neuropsychiatric symptoms (NPS) vary by population in AD. This is likely the result of both sociocultural and genetic ancestral differences. However, the impact of these NPS on AD in different groups is not well understood. METHODS: Self-declared AA, HIW, and NHW individuals were ascertained as part of ongoing AD genetics studies. Participants who scored higher than 0.5 on the Clinical Dementia Rating (CDR) Scale (CDR) were included. Group similarities and differences on Neuropsychiatric Inventory Questionnaire (NPI-Q) outcomes (NPI-Q total score, NPI-Q items) were evaluated using univariate ANOVAs and post hoc comparisons after controlling for sex and CDR stage. RESULTS: Our sample consisted of 498 participants (26% AA; 30% HIW; 44% NHW). Overall, NPI-Q total scores differed significantly between our groups, with HIW having the highest NPI-Q total scores, and by AD stage as measured by CDR. We found no significant difference in NPI-Q total score by sex. There were six NPI-Q items with comparable prevalence in all groups and six items that significantly differed between the groups (Anxiety, Apathy, Depression, Disinhibition, Elation, and Irritability). Further, within the HIW group, differences were found between Puerto Rican and Cuban American Hispanics across several NPI-Q items. Finally, Six NPI-Q items were more prevalent in the later stages of AD including Agitation, Appetite, Hallucinations, Irritability, Motor Disturbance, and Nighttime Behavior. CONCLUSIONS: We identified differences in NPS among HIW, AA, and NHW individuals. Most striking was the high burden of NPS in HIW, particularly for mood and anxiety symptoms. We suggest that NPS differences may represent the impact of sociocultural influences on symptom presentation as well as potential genetic factors rooted in ancestral background. Given the complex relationship between AD and NPS it is crucial to discern the presence of NPS to ensure appropriate interventions.

Cognitive profile of people with mild behavioral impairment in Brain Health Registry participants.

OBJECTIVES: Dementia assessment includes cognitive and behavioral testing with informant verification. Conventional testing is resource-intensive, with uneven access. Online unsupervised assessments could reduce barriers to risk assessment. The aim of this study was to assess the relationship between informant-rated behavioral changes and participant-completed neuropsychological test performance in older adults, both measured remotely via an online unsupervised platform, the Brain Health Registry (BHR). DESIGN: Observational cohort study. SETTING: Community-dwelling older adults participating in the online BHR. Informant reports were obtained using the BHR Study Partner Portal. PARTICIPANTS: The final sample included 499 participant-informant dyads. MEASUREMENTS: Participants completed online unsupervised neuropsychological assessment including Forward Memory Span, Reverse Memory Span, Trail Making B, and Go/No-Go tests. Informants completed the Mild Behavioral Impairment Checklist (MBI-C) via the BHR Study Partner portal. Cognitive performance was evaluated in MBI+/- individuals, as was the association between cognitive scores and MBI symptom severity. RESULTS: Mean age of the 499 participants was 67, of which 308/499 were females (61%). MBI + status was associated with significantly lower memory and executive function test scores, measured using Forward and Reverse Memory Span, Trail Making Errors and Trail Making Speed. Further, significant associations were found between poorer objectively measured cognitive performance, in the domains of memory and executive function, and MBI symptom severity. CONCLUSION: These findings support the feasibility of remote, informant-reported behavioral assessment utilizing the MBI-C, supporting its validity by demonstrating a relationship to online unsupervised neuropsychological test performance, using a previously validated platform capable of assessing early dementia risk markers.

Managing Behavioral and Psychological Symptoms of Dementia (BPSD) in the Era of Boxed Warnings.

PURPOSE OF REVIEW: To provide a comprehensive overview on the evaluation and management of behavioral and psychological symptoms of dementia (BPSD) using evidence from literature. RECENT FINDINGS: Evidence indicates efficacy for some non-pharmacological techniques including education of caregivers and cognitive stimulation therapy and pharmacological agents like antidepressant and antipsychotics for the management of BPSD. The use of antipsychotics has generated controversy due to the recognition of their serious adverse effect profile including the risk of cerebrovascular adverse events and death. BPSD is associated with worsening of cognition and function among individuals with dementia, greater caregiver burden, more frequent institutionalization, overall poorer quality of life, and greater cost of caring for these individuals. Future management strategies for BPSD should include the use of technology for the provision of non-pharmacological interventions and the judicious use of cannabinoids and interventional procedures like ECT for the management of refractory symptoms.

Less Is More: The Impact of Deprescribing Psychotropic Drugs on Behavioral and Psychological Symptoms and Daily Functioning in Nursing Home Patients. Results From the Cluster-Randomized Controlled COSMOS Trial.

OBJECTIVE: To investigate the impact of medication reviews using collegial mentoring and systematic clinical evaluation on psychotropic prescriptions, behavioral and psychological symptoms of dementia (BPSD), and activities of daily living (ADL). DESIGN: Four-month multicenter, multicomponent, cluster-randomized, single-blinded controlled trial. SETTING: Thirty-three Norwegian nursing homes including 67 nursing home wards (clusters). PARTICIPANTS: A total of 723 enrolled patients, of which 428 participated in the study; 217 were randomized to the intervention and 211 to care as usual (control). INTERVENTION: The COSMOS intervention consisted of Communication, Systematic pain management, Medication reviews, Organization of activities, and Safety. During medication review, the nursing home physician evaluated treatment with colleagues systematically using the results from validated clinical assessments. MEASUREMENTS: Mean changes from baseline to month 4 in the number of prescribed psychotropic drugs (antipsychotics, anxiolytics, hypnotics or sedatives, antidepressants, and antidementia drugs); Neuropsychiatric Inventory Nursing Home Version (NPI-NH) and Cornell Scale of Depression in Dementia (CSDD); Lawton and Brody's Physical Self Maintenance Scale (PSMS). RESULTS: Compared to control, the mean change in prescribed psychotropic drugs was reduced both in total and regular number, while mean changes in NPI-NH and CSDD scores did not differ between the groups. Mean change in PSMS showed improvement in the intervention group, and deterioration in the control group. CONCLUSION: Medication reviews using collegial mentoring and systematic clinical evaluation led to safe deprescribing, as the reductions in psychotropic drug use did not negatively affect BPSD, while ADL improved.

Diagnostic criteria for apathy in neurocognitive disorders.

INTRODUCTION: Apathy is common in neurocognitive disorders (NCD) but NCD-specific diagnostic criteria are needed. METHODS: The International Society for CNS Clinical Trials Methodology Apathy Work Group convened an expert group and sought input from academia, health-care, industry, and regulatory bodies. A modified Delphi methodology was followed, and included an extensive literature review, two surveys, and two meetings at international conferences, culminating in a consensus meeting in 2019. RESULTS: The final criteria reached consensus with more than 80% agreement on all parts and included: limited to people with NCD; symptoms persistent or frequently recurrent over at least 4 weeks, a change from the patient's usual behavior, and including one of the following: diminished initiative, diminished interest, or diminished emotional expression/responsiveness; causing significant functional impairment and not exclusively explained by other etiologies. DISCUSSION: These criteria provide a framework for defining apathy as a unique clinical construct in NCD for diagnosis and further research.

General practitioners' knowledge, attitudes, and experiences of managing behavioural and psychological symptoms of dementia: A mixed-methods systematic review.

OBJECTIVES: To synthesise the existing published literature on general practitioners (GP)'s knowledge, attitudes, and experiences of managing behavioural and psychological symptoms of dementia (BPSD) with a view to informing future interventions. METHODS: We conducted a systematic review and synthesis of quantitative and qualitative studies that explored GPs' experiences of managing BPSD (PROSPERO protocol registration CRD42017054916). Seven electronic databases were searched from inception to October 2017. Each stage of the review process involved at least 2 authors working independently. The meta-ethnographic approach was used to synthesise the findings of the included studies while preserving the context of the primary data. The Confidence in the Evidence from Reviews of Qualitative research (CERQual) was used to assess the confidence in our individual review findings. RESULTS: Of the 1638 articles identified, 76 full texts were reviewed and 11 were included. Three main concepts specific to GPs' experiences of managing BPSD emerged: unmet primary care resource needs, justification of antipsychotic prescribing, and the pivotal role of families. A "line of argument" was drawn, which described how in the context of resource limitations a therapeutic void was created. This resulted in GPs being over reliant on antipsychotics and family caregivers. These factors appeared to culminate in a reactive response to BPSD whereby behaviours and symptoms could escalate until a crisis point was reached. CONCLUSION: This systematic review offers new insights into GPs' perspectives on the management of BPSD and will help to inform the design and development of interventions to support GPs managing BPSD.

Apathy associated with neurocognitive disorders: Recent progress and future directions.

INTRODUCTION: Apathy is common in neurocognitive disorders (NCDs) such as Alzheimer's disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities. METHODS: The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Neuropsychiatric Syndromes Professional Interest Area (NPS-PIA) Apathy workgroup reviewed the latest research regarding apathy in NCDs. RESULTS: Progress has recently been made in three areas relevant to apathy: (1) phenomenology, including the use of diagnostic criteria and novel instruments for measurement, (2) neurobiology, including neuroimaging, neuropathological and biomarker correlates, and (3) interventions, including pharmacologic, nonpharmacologic, and noninvasive neuromodulatory approaches. DISCUSSION: Recent progress confirms that apathy has a significant impact on those with major NCD and those with mild NCDs. As such, it is an important target for research and intervention.

Patterns of psychotropic prescribing and polypharmacy in older hospitalized patients in Ireland: the influence of dementia on prescribing.

BACKGROUND: Neuropsychiatric Symptoms (NPS) are ubiquitous in dementia and are often treated pharmacologically. The objectives of this study were to describe the use of psychotropic, anti-cholinergic, and deliriogenic medications and to identify the prevalence of polypharmacy and psychotropic polypharmacy, among older hospitalized patients in Ireland, with and without dementia. METHODS: All older patients (≥ 70 years old) that had elective or emergency admissions to six Irish study hospitals were eligible for inclusion in a longitudinal observational study. Of 676 eligible patients, 598 patients were recruited and diagnosed as having dementia, or not, by medical experts. These 598 patients were assessed for delirium, medication use, co-morbidity, functional ability, and nutritional status. We conducted a retrospective cross-sectional analysis of medication data on admission for 583/598 patients with complete medication data, and controlled for age, sex, and co-morbidity. RESULTS: Of 149 patients diagnosed with dementia, only 53 had a previous diagnosis. At hospital admission, 458/583 patients experienced polypharmacy (≥ 5 medications). People with dementia (PwD) were significantly more likely to be prescribed at least one psychotropic medication than patients without dementia (99/147 vs. 182/436; p < 0.001). PwD were also more likely to experience psychotropic polypharmacy (≥ two psychotropics) than those without dementia (54/147 vs. 61/436; p < 0.001). There were no significant differences in the prescribing patterns of anti-cholinergics (23/147 vs. 42/436; p = 0.18) or deliriogenics (79/147 vs. 235/436; p = 0.62). CONCLUSIONS: Polypharmacy and psychotropic drug use is highly prevalent in older Irish hospitalized patients, especially in PwD. Hospital admission presents an ideal time for medication reviews in PwD.

Neuropsychiatric symptoms in community-dwelling Mexican-Americans: results from the Hispanic Established Population for Epidemiological Study of the Elderly (HEPESE) study.

OBJECTIVE: The Neuropsychiatric Inventory (NPI) is a well-established measure of psychopathology and frequently used in dementia studies. Little is known about its psychometric characteristics at a population level, particularly among Hispanics. We report the frequency of NPI symptoms in a community-dwelling older Mexican-American (MA) population cohort and the degree of symptom-related distress experienced by participant informants. METHODS: Participants were 1079 MA age 80 years and over residing in five southwestern states who were administered the NPI as part of wave-7 of the Hispanic Established Population for Epidemiological Study of the Elderly (HEPESE) conducted from 2010 to 2011. RESULTS: Nine hundred twenty-five informants rated NPI domains. Prevalence of neuropsychiatric symptoms (NPS) varied by symptom domain and ranged from agitation/aggression (32%) to euphoria/elation (5%). The overall rate of behavioral disturbances was 62.7%. On the other hand, 37.3% of informants reported no NPS. A significant fraction of the informants reported distress from the mood disorder cluster of the scale. CONCLUSIONS: A large percentage (>60%) of community-dwelling older MA have one or more informant-reported NPS. These symptoms have diagnostic, prognostic, and therapeutic implications. Although neuropsychiatric disorders may be the initial clinical manifestation of dementia and often appear before cognitive alterations, the high frequency of these symptoms in the HEPESE cohort may reflect a high prevalence of these disorders among community-dwelling MA. The pattern we observed also suggests relatively advanced stages of dementia.

Tau-PET in early cortical Alzheimer brain regions in relation to mild behavioral impairment in older adults with either normal cognition or mild cognitive impairment.

Mild Behavioral Impairment (MBI) leverages later-life emergent and persistent neuropsychiatric symptoms (NPS) to identify a high-risk group for incident dementia. Phosphorylated tau (p-tau) is a hallmark biological manifestation of Alzheimer disease (AD). We investigated associations between MBI and tau accumulation in early-stage AD cortical regions. In 442 Alzheimer's Disease Neuroimaging Initiative participants with normal cognition or mild cognitive impairment, MBI status was determined alongside corresponding p-tau and Aß. Two meta-regions of interest were generated to represent Braak I and III neuropathological stages. Multivariable linear regression modelled the association between MBI as independent variable and tau tracer uptake as dependent variable. Among Aß positive individuals, MBI was associated with tau uptake in Braak I (ß=0.45(0.15), p<.01) and Braak III (ß=0.24(0.07), p<.01) regions. In Aß negative individuals, MBI was not associated with tau in the Braak I region (p=0.11) with a negative association in Braak III (p=.01). These findings suggest MBI may be a sequela of neurodegeneration, and can be implemented as a cost-effective framework to help improve screening efficiency for AD.

Common Neuropsychiatric S ymptoms in Alzheimer's Disease, Mild Cognitive Impairment, and Subjective Memory Complaints: A Unified Framework.

The Alzheimer's disease (AD) continuum is a unique spectrum of cognitive impairment that typically involves the stages of subjective memory complaints (SMC), mild cognitive impairment (MCI), and AD dementia. Neuropsychiatric symptoms (NPS), such as apathy, anxiety, stress, and depression, are highly common throughout the AD continuum. However, there is a dearth of research on how these NPS vary across the AD continuum, especially SMC. There is also disagreement on the effects of specific NPS on each stage of the AD continuum due to their collinearity with other NPS, cognitive decline, and environmental factors (e.g., stress). In this article, we conduct a novel perspective review of the scientific literature to understand the presence of NPS across the AD continuum. Specifically, we review the effects of apathy, depression, anxiety, and stress in AD, MCI, and SMC. We then build on this knowledge by proposing two theories of NPS' occurrence across the AD continuum. Consequently, we highlight the current landscape, limitations (e.g., differing operationalization), and contentions surrounding the NPS literature. We also outline theories that could clear up contention and inspire future NPS research.

Neuropsychiatric disturbance detecting polycythemia vera myelofibrosis: a case report and literature review.

Background: Neuropsychiatric disturbances and chorea are less recognized consequences of polycythemia vera (PV), and their role in post-PV myelofibrosis (MF) has not been reported. Clinical features that predict post-PV MF lack specificity. Case presentation: We describe an elderly patient with PV who developed acute-onset reversible neuropsychiatric disturbances accompanied by generalized chorea and was finally diagnosed with post-PV MF after a bone marrow examination. We also reviewed four cases of late PV associated with neuropsychiatric symptoms since 1966 and analyzed their clinical characteristics and therapeutic effects. Conclusion: Our case indicates that Janus kinase 2 (JAK2)-related PV is a treatable cause of late-onset chorea and that chorea may herald the deterioration of hematological parameters. Our case provides a clinically specific representation of post-PV MF. Patients with a long course of PV are recommended to undergo bone marrow re-examinations when they present with neuropsychiatric symptoms to achieve an early diagnosis of post-PV MF.

Neuropsychiatric Presentations due to Traumatic Brain Injury in Cognitively Normal Older Adults.

Neuropsychiatric symptoms (NPS) are common sequelae of traumatic brain injuries (TBI) among adults. However, little is known about NPS associated with a history of TBI in adults relative to adults without a history of TBI and to what extent NPS may be modulated by sex and other factors. Using the National Alzheimer's Coordinating Center Uniform Data Set, we examined the association between Neuropsychiatric Inventory-Questionnaire (NPI-Q) scores in cognitively normal older adults with and without a history of TBI. A binomial logistic regression model was used to examine NPI-Q domains in adults with a history of TBI (n = 266) versus without a history of TBI (n = 1508). History of TBI, sex, age, and body mass index were used as covariates. Adults with a history of TBI had a greater probability of exhibiting agitation, anxiety, apathy, disinhibition and aberrant motor behavior relative to adults without a history of TBI. In terms of sex differences, males with and without a history of TBI had an increased likelihood of agitation, apathy, disinhibition, and apnea, whereas females had an increased likelihood of anxiety and insomnia relative to males. Our study confirms that history of TBI is associated with an increased prevalence of specific NPS, including agitation, anxiety, apathy, disinhibition, and aberrant motor behavior. Given that the aforementioned NPS are linked through different pathways, damage to any of them may cause an alteration in behavior. As well, NPS appear to be modulated by sex, with symptoms differing between males and females. Our research suggests future studies examining NPS sequelae of TBI should adjust for sex.

Progression of neuropsychiatric symptoms in young-onset versus late-onset Alzheimer's disease.

Young-onset and late-onset Alzheimer's disease has different clinical presentations with late-onset presenting most often with memory deficits while young-onset often presents with a non-amnestic syndrome. However, it is unknown whether there are differences in presentation and progression of neuropsychiatric symptoms in young- versus late-onset Alzheimer's disease. We aimed to investigate differences in the prevalence and severity of neuropsychiatric symptoms in patients with young- and late-onset Alzheimer's disease longitudinally with and without accounting for the effect of medication usage. Sex differences were also considered in these patient groups. We included 126 young-onset and 505 late-onset Alzheimer's disease patients from National Alzheimer's Coordinating Center-Uniform Data Set (NACC-UDS) and Alzheimer's Disease Neuroimaging Initiative (ADNI). We investigated the prevalence and severity of neuropsychiatric symptoms using the Neuropsychiatric Inventory-Questionnaire over 4 visits with 1-year intervals, using a linear mixed-effects model. The prevalence of depression was significantly higher in young-onset than late-onset Alzheimer's disease over a 4-year interval when antidepressant usage was included in our analyses. Our findings suggest that neuropsychiatric symptom profiles of young- and late-onset Alzheimer's disease differ cross-sectionally but also display significant differences in progression.

Pharmacological treatment of neuropsychiatric symptoms of dementia: a network meta-analysis protocol.

BACKGROUND: Neuropsychiatric symptoms (NPS) of dementia are a common issue in dementia patients which can lead to poor medical and functional outcomes. Pharmacological interventions are its treatment of choice. However, whether to use pharmacological treatments in this population and which drug should be preferred remain controversial. We therefore aimed to compare and rank pharmacological interventions for NPS according to their efficacy and acceptability profiles by quantifying information from randomized controlled trials (RCTs). METHODS: We will include all RCTs reported as double-blind and comparing one active drug with another or with placebo that compare cholinesterase inhibitors (ChEIs), N-methyl-D-aspartic acid (NMDA) receptor modulators, antipsychotics, antidepressants, and mood stabilisers. Studies will be retrieved by searching electronic databases, including Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, Clinicaltrial.govs, EMBASE, and with no date or language restrictions. The primary outcomes were efficacy (change in overall symptoms) and acceptability (all-cause discontinuation). The network meta-analysis (NMA) will be conducted in R software within a Bayesian framework. The quality of evidence will be evaluated using the Cochrane risk of bias tool, and the GRADE approach. We will conduct subgroup analyses to assess the robustness of our findings. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSIONS: This systematic review will synthesize the available evidence on the comparative efficacy of different pharmacological approaches in the management of overall NPS, agitation, psychosis, apathy and depressive symptoms in dementia patients. The results of the present NMA will influence evidence-based treatment decisions for clinicians.

Neuropsychiatric Symptoms and Risk Factors in Mild Cognitive Impairment: A Cohort Investigation of Elderly Patients.

BACKGROUND: Neuropsychiatric symptoms (NPS) have been shown to affect the progression and development of Alzheimer's disease (AD) in the elderly. However, the published data are still controversial and limited in large cohort-based NPS study. AIM: To explore the potential relationship between NPS and mild cognitive impairment (MCI) among the elderly of Chinese community. METHODS: A total of 465 Chinese community-dwelling elderly (age ≥ 60 years) with mild cognitive impairment (MCI) were recruited into this investigation. At baseline, enrolled participants were assessed for Clinical Dementia Rating (CDR), mini-psychiatric examination. They were also subjected to categorical language fluency test, list learning and delayed recall. We assessed the NPS severity by Neuropsychological Inventory (NPI). The global cognitive status (GCS) of the participants at the end of the 3-year study period were measured with the CDR. RESULTS: Approximately 41.6% of subjects had 1 or more NPS (total NPI score ≥ 1) at baseline. The most common NPSs were nocturnal behavior (20.8%), depression (17.3%), apathy (12.7%) and anxiety (13.2%). At the end of 3-year follow-up, 26.9% of baseline depressed patients developed AD, while 15.2% of baseline non-depressed patients developed AD (χ2 = 4.86, P=0. 04). Abnormal motor behavior was significantly correlated with cognitive deterioration as well (χ2 = 5.75, P=0. 03). Logistic regression analysis revealed that depression was considered as a risk factor for AD progression at baseline (95% CI: 1.12-5.67, OR=2.37, P=0.03). CONCLUSIONS: Depression may be an independent factor representing early neurodegeneration in elder patients with MCI. Further studies are warranted to assess whether effective management of NPS promotes the cognitive functions.

Effects of neuropsychiatric symptoms of dementia on reductions in activities of daily living in patients with Alzheimer's disease.

AIM: In patients with Alzheimer's disease (AD), cognitive impairments cause a progressive reduction in Activities of Daily Living (ADL). Neuropsychiatric symptoms (NPS) also appear in most patients; however, the association between NPS and reductions in ADL remains unclear. The present study evaluated whether NPS influence such reductions using two different ADL measures in patients with AD. METHODS: Among 546 consecutive outpatients who visited the memory clinic at the Jikei University Kashiwa Hospital, we recruited 208 patients with AD and investigated the correlations between either the Physical Self-Maintenance Scale (PSMS) score or the Instrumental ADL (IADL) level, and each of the Behavioral Pathology in AD (Behave-AD) subscales. To clarify the causal relationships of these correlations, we then verified the associations between statistically significant demographic variables and the Behave-AD subscales as well as the two ADL scales (PSMS score and IADL percentage) using a general linear model. RESULTS: Neither the PSMS nor the IADL results were significantly influenced by the aberrant motor behaviors score. However, the IADL was significantly influenced by the Mini-Mental State Exam (MMSE) score. Furthermore, diurnal rhythm disturbances and the interaction between diurnal rhythm disturbances score and the MMSE score significantly influenced the PSMS results. CONCLUSION: Basic ADL reductions may be influenced by diurnal rhythm disturbances, in addition to cognitive impairments in patients with AD. Furthermore, the interaction between the diurnal rhythm disturbances score and cognitive function may also influence basic ADL. Geriatr Gerontol Int 2020; ••: ••-••.

Behavioural and psychological symptoms of dementia in mouse models of Alzheimer's disease-related pathology.

Transgenic mouse models have been used extensively to model the cognitive impairments arising from Alzheimer's disease (AD)-related pathology. However, less is known about the relationship between AD-related pathology and the behavioural and psychological symptoms of dementia (BPSD) commonly presented by patients. This review discusses the BPSD-like behaviours recapitulated by several mouse models of AD-related pathology, including the APP/PS1, Tg2576, 3xTg-AD, 5xFAD, and APP23 models. Current evidence suggests that social withdrawal and depressive-like behaviours increase with progressive neuropathology, and increased aggression and sleep-wake disturbances are present even at early stages; however, there is no clear evidence to support increased anxiety-like behaviours, agitation (hyperactivity), or general apathy. Overall, transgenic mouse models of AD-related pathology recapitulate some of the BPSD-like behaviours associated with AD, but these behaviours vary by model. This reflects the patient population, where AD patients typically exhibit one or more BPSD, but rarely all symptoms at once. As a result, we suggest that transgenic mouse models are an important tool to investigate the pathology underlying BPSD in human AD patients.

Advances in Management of Psychosis in Neurodegenerative Diseases.

PURPOSE OF THE REVIEW: Psychosis is broadly defined as a disengagement from reality. It describes syndromes that impair both thought content and thought process. Psychosis negatively impacts an individual's quality of life, in addition to the families caring for them. Psychosis with different types of hallucinations and delusions occurs in the context of delirium. Neuropsychiatric symptoms (NPS) are almost universal in the course of common neurodegenerative disorders (NDD) like Alzheimer's disease (AD) or Parkinson's disease (PD). In this paper, the authors took an effort to characterize AD and PD psychosis with a special focus on the most diagnostically reliable features. Effectiveness and limitations of pharmacological interventions are discussed. RECENT FINDINGS: Consensus diagnostic criteria have evolved for psychosis secondary to AD as well as psychosis in PD. Psychotropic medications can be effective in the treatment of NPS in NDD; however, clinicians must be mindful of the side effects. There is a consensus on benefit of initiating any acetylcholinesterase inhibitor (ACHI: donepezil, rivastigmine, and galantamine) as a first line of treatment for psychosis in AD, as it may reduce and/or avoid the need for the use antipsychotics. Pimavanserin, a selective-serotonin inverse agonist that preferentially targets 5-HT2A receptors, while avoiding activity at dopamine and other receptors commonly targeted by antipsychotics had recently been approved by FDA to treat hallucinations and delusions in PD. Quetiapine is widely prescribed for the treatment of psychosis in different NDD, but the data remains equivocal. Psychosis with different types of hallucinations and delusions may occur in the context of delirium and is almost universal as a neuropsychiatric symptom in the course of PD and AD. Currently, pimavanserin remains the only pharmacologic agent approved for treatment of psychosis in PD. In cases of other NPS in other than Parkinson's diseases, atypical antipsychotics are commonly used off-label. More research is greatly needed to advance this field and address NPS especially psychosis in geriatric population.