Efficacy and Safety of Cannabinoids for Neuropsychiatric Symptoms of Dementia: A Systematic Review with Meta-analysis.

Exercise interventions ameliorate neuropsychiatric symptoms in dementia: A meta-analysis

The authors aim to determine if a history of traumatic brain injury (TBI) assessed before dementia onset is associated with a higher risk of neuropsychiatric symptoms after dementia onset. A population-based incident series of people with dementia were assessed for TBI prior to onset of dementia and for neuropsychiatric symptoms after the onset, using the Neuropsychiatric Inventory. Participants with predementia TBI were more likely to exhibit disinhibition (12.7% versus 5.4%, OR=2.8, p=0.02), but not other neuropsychiatric symptoms. Traumatic brain injury may increase the risk of disinhibition in patients with dementia.

A systematic review of the novel applications of cannabinoids in dementia care: food refusal and neuropsychiatric symptoms

Pharmacological treatments are very common to be used for alleviating neuropsychiatric symptoms (NPS) in dementia. However, decision on drug selection is still a matter of controversy. To summarise the comparative efficacy and acceptability of currently available monotherapy drug regimens for reducing NPS in dementia. We searched PubMed, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials between inception and 26 December 2022 without language restrictions; and reference lists scanned from selected studies and systematic reviews. Double-blind randomised controlled trials were identified from electronic databases for reporting NPS outcomes in people with dementia. Primary outcomes were efficacy and acceptability. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). We included 59 trials (15,781 participants; mean age, 76.6years) and 15 different drugs in quantitative syntheses. Risperidone (standardised mean difference [SMD] -0.20, 95% credible interval [CrI] -0.40 to -0.10) and galantamine (-0.20, -0.39 to -0.02) were more effective than placebo in short-term treatment (median duration: 12weeks). Galantamine (odds ratio [OR] 1.95, 95% CrI 1.38-2.94) and rivastigmine (1.87, 1.24-2.99) were associated with more dropouts than placebo, and some active drugs. Most of the results were rated as low or very low according to CINeMA. Despite the scarcity of high-quality evidence, risperidone is probably the best pharmacological option to consider for alleviating NPS in people with dementia in short-term treatment when considering the risk-benefit profile of drugs.

ABSTRACTBackgroundPrevious studies of community‐dwelling people with Alzheimer's disease (AD) have reported an association between the severe neuropsychiatric symptoms (NPS) of dementia and caregiver burden. We explored the current status of family caregiver burden, NPS of dementia, and care service usage in Japanese community‐dwelling people with AD.MethodsA web‐based questionnaire was administered to cohabitant family caregivers of community‐dwelling people with AD from 13 to 27 November 2023. Amongst 8108 participants registered in the panel data, 705 family caregivers (age: 19–79 years) were selected. Participants completed the Japanese version of the Neuropsychiatric Inventory‐Brief Questionnaire.ResultsFamily caregivers (n = 705) had a mean ± standard deviation (SD) age of 54.6 ± 11.5 years, 56.9% were male, and 84.0% cared for a parent or in‐law with AD. Patients with AD had a mean ± SD age of 84.2 ± 8.8 years; 26.2% were male, and 90.6% had NPS, including 73.4% with hyperactivity (agitation, disinhibition, irritability and aberrant motor behaviour). Mean ± SD caregiving time per week was higher for caregivers of patients with NPS versus without NPS (24.1 ± 22.1 vs. 17.6 ± 14.0 h). The dissatisfaction with nursing care support services was higher amongst caregivers of patients with NPS vs. without NPS. To manage hyperactivity, 11.3% of caregivers administered medication and 11.5% relocated patients to a calm environment; 16.6% of the caregivers had no way to cope. Amongst caregivers who responded ‘administer medication’ in response to hyperactivity, 32.1% had care staff or a medical provider come in and administer oral medication and 18.9% took the patient to a medical facility to receive an injection or intravenous treatment.ConclusionsCaregiving for AD patients with NPS (vs. without NPS) was associated with longer duration of caregiving, greater usage of nursing care services and dissatisfaction with nursing care support services.

To understand the relationship between social determinants of health (SDoH) and neuropsychiatric symptoms (NPS) of dementia and mild cognitive impairment (MCI) such as depression, agitation, psychosis, and apathy. The study extracted data from papers published before January 27, 2025, from PubMed, PsycINFO, and Embase. A total of 2034 articles were identified, and after critical assessment, 18 articles were included in our narrative review. Of the 18 studies, 14 assessed the relationship between NPS and SDoH in participants with dementia, one studied participants with MCI, and three studied those with either dementia or MCI. The majority of the studies (n = 10) had a cross-sectional design, while others had a longitudinal design. Most studies (n = 13) used the Neuropsychiatric Inventory (NPI) or its variants for measuring NPS. Education (n = 8) was the most studied SDoH, with studies overall showing that more education is associated with less NPS (n = 4), although some studies showed mixed (n = 1), null (n = 1), and reverse (n = 2) associations. Studies showed that increased social connectedness and marriage overall was associated with decreased NPS (4 out of 6 studies). Two studies showed that increased religiosity and spirituality was associated with decreased NPS. Poor nutrition, and immigrant status/speaking English as a second language were associated with increased NPS. This narrative review shows that while several studies report an association between SDoHs and NPS in dementia and MCI, more studies are needed to understand the relationship, particularly elucidating how it affects different symptoms of NPS. That could inform clinical practice and public policy. Future studies also need to focus on understanding the causality of the relationship and possible interventions.

The purpose of this research was to assess the frequency and severity of neuropsychiatric and behavioral symptoms and to examine the association between preexisting medical conditions and specific neuropsychiatric symptoms in demented individuals. We studied 211 demented subjects (87.7 percent male) who were participants in epidemiological studies of dementia. Using the Neuropsychiatric Inventory (NPI), we assessed the frequency and severity of neuropsychiatric symptoms. We collected medical history information during a structured telephone interview. Our analyses focused on determining prevalence of neuropsychiatric symptoms by dementia diagnosis and severity. We also examined the association of history of head injury, alcohol abuse, and stroke with development of neuropsychiatric symptoms. We found that neuropsychiatric symptoms were common, with approximately three-fourths of the subjects exhibiting at least one symptom during the preceding month. Apathy (39.3 percent), agitation (31.8 percent), and aberrant motor behavior (31.1 percent) were the most frequent symptoms. Frequency and severity of symptoms were similar for the all-dementia and Alzheimer's disease-only groups, neuropsychiatric symptoms varied by severity of dementia, but generally not in a consistent ordinal pattern. History of alcohol abuse, head injury, or stroke was associated with presence of specific neuropsychiatric symptoms in dementia. While psychiatric symptoms are common in dementia, they also vary by type and severity of dementia. The finding that certain medical conditions may increase risk for specific types of neuropsychiatric symptoms expands our knowledge of the natural history of dementia and should improve management of dementia in medically ill patients. Our results may also shed light on mechanisms that underlie neuropsychiatric symptoms.

PurposeRun‐in periods are used to identify placebo‐responders and washout. Our aim was to assess the association of run‐in periods with clinical outcomes of antipsychotics in dementia.MethodsWe searched randomized placebo‐controlled trials of conventional and atypical antipsychotics for neuropsychiatric symptoms (NPS) in dementia in electronic sources and references of selected articles. We extracted (a) the presence of a run‐in period, use of placebo/investigated drug during run‐in (versus washout only), and run‐in duration (1 week or more) and (b) the reduction in NPS, number of participants with somnolence, extrapyramidal symptoms (EPS), and deaths per treatment group. We pooled clinical outcomes comparing antipsychotic and placebo groups in trials with and without run‐in.ResultsWe identified 35 trials. Twenty‐nine trials used run‐in. The pooled standardized mean difference in the reduction of NPS was −0.170 (95% CI, −0.227 to −0.112) in trials with run‐in and −0.142 (95% CI, −0.331 to 0.047) in trials without run‐in. The pooled odds ratio for somnolence was 2.8 (95% CI, 2.3‐3.5) in trials with run‐in and 3.5 (95% CI, 1.2‐10.7) in trials without run‐in; for EPS, these ORs were 1.8 (95% CI, 1.4‐2.2) and 2.0 (95% CI, 1.3‐3.1) respectively, and for mortality 1.4 (95% CI, 1.0‐2.0) and 1.6 (95% CI, 0.7‐3.4). The use of placebo/investigated drug during run‐in and run‐in duration did not affect the estimates in a consistent way.ConclusionsThe use of run‐in in trials might have led to overestimated efficacy and especially underestimated risks of side effects of antipsychotics compared with placebo for NPS in dementia.

BackgroundKnowledge about treatment status can influence effects measured in trials when subjective scales are used.ObjectiveThe aim of this study was to compare subjective outcomes with objective outcomes of conventional and atypical antipsychotics for neuropsychiatric symptoms (NPS) in dementia.MethodsWe performed a meta-epidemiological study of 38 randomized, placebo-controlled trials. For effectiveness, we used change in NPS and response rate as subjective outcomes, while overall dropout and additional psychotropic use were used as objective outcomes. For side effects, extrapyramidal symptoms (EPS) and somnolence were used as subjective outcomes, while dropout due to adverse events, medication use for EPS, and participants falling were used as objective outcomes.ResultsConventional antipsychotics reduced NPS more than placebo (standardized mean difference [SMD] − 0.36, 95% confidence interval [CI] − 0.49 to − 0.23), as did atypical antipsychotics (SMD − 0.14, 95% CI − 0.19 to − 0.08). Response rates in the drug groups were also higher. Overall dropout did not differ between conventional antipsychotics and placebo (odds ratio [OR] 1.03, 95% CI 0.77–1.37) or atypical antipsychotics and placebo (OR 1.01, 95% CI 0.89–1.14). Furthermore, additional psychotropic use did not differ. The risk of EPS was higher for conventional (OR 2.93, 95% CI 2.04–4.22) and atypical antipsychotics (OR 1.52, 95% CI 1.23–1.88) versus placebo, as was the risk of somnolence and dropout due to adverse events, but medication use for EPS, as well as risk of falls, was not.ConclusionsThe effectiveness of antipsychotics for NPS in dementia based on subjective scales was not confirmed using objective outcomes, in contrast to the increased risk of side effects.

Neuropsychiatric symptoms (NPS) in dementia are frequent and challenging for patients, carers, and the health care system, but few long-term studies exist. We analyse the longitudinal course of NPS in patients with mild dementia. A longitudinal cohort study of 223 patients with mild dementia and annual assessments using the Neuropsychiatric Inventory (NPI) for 5years. A total 1043 NPI assessments, representing 97% of all possible measurements of living cohort members, were analysed. Neuropsychiatric symptoms were common at baseline, and only a moderate increase in total NPS score from 15 to 17 with no increase in the proportion with high NPI total scores. Ninety seven percent scored ≥16, and 49% scored ≥36 on NPI total score at least once during follow-up. Individual NPS fluctuated and often reappeared. The most common symptoms ever reported was apathy (83%), depression (63%), appetite (63%), and aberrant motor behavior (60%). Cognitive decline was associated with higher NPI total score and several NPI items, but only the frequency of apathy increased significantly with time. Lewy body dementia was associated with higher NPI total score and psychotic symptoms. Alzheimer's disease was associated with increase in apathy. Severe NPS are already common at time of dementia diagnosis, and the increase in overall severity over 5years was moderate. Individual symptoms tend to fluctuate over time within patients and correspond to states rather than traits. These findings highlight the need to focus on, and plan for, NPS as part of dementia pathway, and are relevant for clinical trial design.

BackgroundThe underlying disease mechanism of neuropsychiatric symptoms (NPS) in dementia remains unclear. Cerebrospinal fluid (CSF) biomarkers for synaptic and axonal degeneration may provide novel neuropathological information for their occurrence. The aim was to investigate the relationship between NPS and CSF biomarkers for synaptic (neurogranin [Ng], growth-associated protein 43 [GAP-43]) and axonal (neurofilament light [NFL]) injury in patients with dementia.MethodsA total of 151 patients (mean age ± SD, 73.5 ± 11.0, females n = 92 [61%]) were included, of which 64 had Alzheimer’s disease (AD) (34 with high NPS, i.e., Neuropsychiatric Inventory (NPI) score > 10 and 30 with low levels of NPS) and 18 were diagnosed with vascular dementia (VaD), 27 with mixed dementia (MIX), 12 with mild cognitive impairment (MCI), and 30 with subjective cognitive impairment (SCI). NPS were primarily assessed using the NPI. CSF samples were analyzed using enzyme-linked immunosorbent assays (ELISAs) for T-tau, P-tau, Aβ1–42, Ng, NFL, and GAP-43.ResultsNo significant differences were seen in the CSF levels of Ng, GAP-43, and NFL between AD patients with high vs low levels of NPS (but almost significantly decreased for Ng in AD patients < 70 years with high NPS, p = 0.06). No significant associations between NPS and CSF biomarkers were seen in AD patients. In VaD (n = 17), negative correlations were found between GAP-43, Ng, NFL, and NPS.ConclusionOur results could suggest that low levels of Ng may be associated with higher severity of NPS early in the AD continuum (age < 70). Furthermore, our data may indicate a potential relationship between the presence of NPS and synaptic as well as axonal degeneration in the setting of VaD pathology.

Neuropsychiatric symptoms (NPS) such as aggression, apathy, agitation, and wandering may occur in up to 90%of dementia cases. International guidelines have suggested that non-pharmacological interventions are as effective as pharmacological treatments, however without the side effects and risks of medications. An occupational therapy method, called Tailored Activity Program (TAP), was developed with the objective to treat NPS in the elderly with dementia and has been shown to be effective. Evaluate the efficacy of the TAP method (outpatient version) in the treatment of NPS in individuals with dementia and in the burden reduction of their caregivers. This is a randomized, double-blind, controlled clinical trial for the treatment of NPS in dementia. Outcome measures consisted of assessing the NPS of individuals with dementia, through the Neuropsychiatric Inventory-Clinician rating scale (NPI-C), and assessing the burden on their caregivers, using the Zarit Scale. All the participants were evaluated pre-and post-intervention. 54 individuals with dementia and caregivers were allocated to the experimental (n = 28) and control (n = 26) groups. There was improvement of the following NPS in the experimental group: delusions, agitation, aggressiveness, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor disturbance, and aberrant vocalization. No improvement was observed in hallucinations, sleep disturbances, and appetite disorders. The TAP method for outpatient settings was also clinically effective in reducing burden between caregivers of the experimental group. The use of personalized prescribed activities, coupled with the caregiver training, may be a clinically effective approach to reduce NPS and caregiver burden of individuals with dementia.

This aim of this study was to examine the mechanisms underlying the neuropsychiatric symptoms in dementia with Lewy bodies by investigating regional cerebral blood flow. Participants were 27 patients who fulfilled the diagnostic criteria for probable dementia with Lewy bodies. All subjects underwent single-photon emission computed tomography scans using technetium-99 m hexamethylpropyleneamine oxime. Neuropsychiatric symptoms were evaluated by neuropsychiatric inventory. Multiple regression analyses using neuropsychiatric inventory and voxel-based analyses of covariance of the regional cerebral blood flow images between subjects with or without each neuropsychiatric symptom were performed. Additionally, similar voxel-based analyses of covariance between subjects with each neuropsychiatric symptom and normal subjects were performed. There were no significant correlations in any psychiatric symptoms in multiple regression analyses. All subjects had hallucination but none had euphoria. We analyzed eight neuropsychiatric symptom scores with the exception of hallucination and euphoria using voxel-based analyses of covariance. Significant differences of regional cerebral blood flow were shown in groups with agitation, disinhibition, and irritability. Subjects with agitation showed hypoperfusion in the parietal lobule, the precuneus, and the angular gyrus, and hyperperfusion in the fusiform gyrus, the lingual gyrus, and the thalamus. Subjects with disinhibition showed hypoperfusion in the left frontal gyrus. Subjects with irritability showed hyperperfusion in the right frontal gyrus. There were no significant differences in regional cerebral blood flow between subjects with any neuropsychiatric symptoms and normal subjects. This study reveals that dysfunction of specific brain regions is associated with various neuropsychiatric symptoms in dementia with Lewy bodies.

Degenerative forms of dementia are progressive, incurable, fatal, and likely to cause suffering in conjunction with personal incapacity. Timely diagnostic disclosure and counseling can facilitate important advance care planning. The risk of harm associated with neuropsychiatric symptoms (NPS) of dementia often has to be balanced against the risk of harm associated with medication management of NPS. A palliative care framework can help preserve autonomy, quality of life, comfort, and dignity for patients with NPS.

To assess the efficacy and adverse reactions of typical and atypical antipsychotics in the treatment of neuropsychiatric symptoms in dementia, and to examine the evidence for the cerebrovascular events warning for atypical antipsychotics. Systematic review. Using Medline, Cinahl, PsyclNFO, Embase and the Cochrane central register of controlled trials (1980-2005), double-blind randomized controlled trials with intention-to-treat analysis were selected, which evaluated efficacy and adverse reactions of antipsychotics in the treatment of neuropsychiatric symptoms in dementia. The studies underwent a standardised validity assessment. After screening 950 studies, 14 studies on the effect of haloperidol, risperidone, olanzapine, quetiapine, tiapride, loxapine and perphenazine were selected. In 7 out of 10 studies, haloperidol, risperidone and olanzapine appeared to be more effective than placebo in the treatment of aggression and psychosis. Direct comparison between typical and atypical antipsychotics revealed no statistically significant difference. The most common adverse reactions were extrapyramidal symptoms and somnolence. These adverse reactions were less frequent with low-dose risperidone than with haloperidol or olanzapine, but risperidone and olanzapine were found to be associated with a higher risk of cerebrovascular events in two studies. The efficacy of typical and atypical antipsychotics is comparable, but only low-dose risperidone seems to be associated with fewer (extrapyramidal) side effects. The adverse reactions are inadequately described in the published data and consequently the warning of an increased risk of mortality could not be confirmed.