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Suicide has been identified as a leading cause of premature death in autistic populations. Elevated autistic traits have also been associated with higher rates of self-harm, suicidal ideation, and suicidal self-harm in the general population, but this has yet to be examined in older age. Using baseline cross-sectional data from the PROTECT study, middle-age and older adults with high autistic traits (n = 276) had significantly higher rates of suicidal ideation, deliberate self-harm, and suicidal self-harm than an age/sex-matched comparison group (n = 10,495). These differences represented a 5- to 6-fold increase in likelihood for self-harming and suicidality. These findings, which remained when controlling for depression symptoms, suggest that middle-age and older adults with high autistic traits may be particularly at risk of self-harm and suicidal behaviours. [ABSTRACT FROM AUTHOR]

Introduction Cognitive training (CT) offers a potential approach for dementia prevention and maintenance of cognitive function in older adults. Online delivery provides a cost-effective means of implementing CT compared with in-person interventions, with the potential of providing an effective public health intervention for risk reduction. Methods A double-blind 6-month online randomized controlled trial in adults older than 50 randomized to General CT, Reasoning CT, or control. The primary outcome was instrumental activities of daily living (IADL) in adults older than 60. Secondary outcomes were reasoning, verbal short-term memory, spatial working memory, verbal learning (VL), and digit vigilance in adults older than 50. Secondary analyses were performed with a group defined as showing age-associated impairment in reasoning according to baseline scores in this domain. Results A total of 2912 adults older than 60 (6742 > 50) participated. General and reasoning packages conferred benefit to IADL ( P = .008, P = .011), reasoning ( P < 0.0001, P < .0001), and VL ( P = .007, P = .008) at 6 months. Benefit in reasoning was evident from 6 weeks. Other benefits developed over 6 months. Analysis of participants with age-associated impairment also showed the same pattern of benefit. A clear dose-response effect was seen. Conclusions Online CT confers significant benefit to cognition and function in older adults, with benefit favoring the Reasoning package. Scale of benefit is comparable with in-person training, indicating its potential as a public health intervention. Impact on the group with age-associated impairment indicates a particular sensitivity to this at-risk group, which merits further investigation. [ABSTRACT FROM AUTHOR]

Introduction There is evidence that neurofibrillary tangle (NFT) burden is associated with psychotic symptoms in Alzheimer disease (AD). However, it is not clear whether this association is direct or mediated through the increased cognitive impairment associated with NFTs. Methods We sought to determine whether the extended MAPT haplotype was associated with the worsening of delusions and hallucinations in a combined cohort of 95 patients who participated in 2 clinical trials of treatment with memantine. Results After controlling for baseline dementia severity, exposure to memantine, and antipsychotics, analysis shows that carriers of at least one H2 allele had a 5.4-fold ( P = .03) increased risk of worsening hallucinations. There was some evidence of association with worsening delusions but only in analysis by allele. Conclusion These results are the first to indicate that the H2 allele of the extended MAPT haplotype negatively affects the course of psychotic symptoms in AD independently of disease severity. It will be important for future research to examine MAPT transcription in people with AD with and without psychotic symptoms to understand the exact mechanisms underlying these findings. [ABSTRACT FROM AUTHOR]

Background: The accumulation of age‐associated cognitive deficits can lead to Mild Cognitive Impairment (MCI) and dementia. This is a major public health issue for the modern ageing population, as it impairs health, independence and overall quality of life. Keeping the brain active during life has been associated with an increased cognitive reserve, therefore reducing the risk of cognitive impairment in older age. Previous research has identified a potential relationship between musicality and cognition. Objectives: Explore the relationship between musicality and cognitive function in a large cohort of older adults. Methods: This was a nested study within the PROTECT‐UK cohort, which collects longitudinal computerised assessments of cognitive function in adults over 40. Participants were invited to complete the validated Edinburgh Lifetime Musical Experience Questionnaire (ELMEQ) to assess their musical experience and lifetime exposure to music. Linear regression analysis was performed using cognitive data from PROTECT‐UK. Results: Analysis identified an association between musicality and cognition in this cohort. Playing a musical instrument was associated with significantly better performance in working memory and executive function. Significant associations were also found between singing and executive function, and between overall musical ability and working memory. Conclusions: Our findings confirm previous literature, highlighting the potential value of education and engagement in musical activities throughout life as a means of harnessing cognitive reserve as part of a protective lifestyle for brain health. Key points: Playing a musical instrument was associated with significantly better working memory and executive function.Singing and overall musical ability was associated with more favourable cognition.Engagement with musical activities should be considered as part of public health initiatives to promote a protective lifestyle for brain health. [ABSTRACT FROM AUTHOR]

Objectives The bidirectionality between self-perceptions of aging and health-related outcomes may depend on age group. Therefore, we tested such bidirectionality among individuals in late midlife (50–64 years), young-old age (65-74 years), and old-old age (75+ years), taking advantage of the construct of Awareness of Age-Related Change (AARC) and its 2-dimensionality in terms of AARC-gains and AARC-losses. Various conceptualizations of physical, mental, and cognitive functioning were used as outcomes. Methods Data from 2 measurement occasions (2019 and 2020) from the UK PROTECT study for individuals in late midlife (N = 2,385), young-old age (N = 2,430), and old-old age (N = 539) were used. Data on self-reported functional difficulties, depression, anxiety, and performance on four computerized cognitive tasks (i.e. verbal reasoning, paired associate learning, self-ordered search, and digit span) providing a score for verbal reasoning and a score for working memory were analyzed using cross-lagged panel models. Results Across all 3 age groups, the bidirectional associations of AARC-gains with indicators of functioning were not significant, whereas higher AARC-losses significantly predicted slightly greater functional difficulties and higher depression and anxiety levels. Higher AARC-losses predicted slightly poorer Verbal Reasoning only in old-old age and poorer Working Memory predicted slightly higher AARC-losses only in young-old age. The remaining associations of AARC-losses with cognitive tasks were not statistically significant. Discussion In accordance with previous research targeting other indicators of self-perceptions of aging, this study supported a stronger impact of AARC-losses on indicators of physical functioning and mental health than vice versa from midlife to old-old age. [ABSTRACT FROM AUTHOR]

Objective: Sleep is vital for normal cognitive function in daily life, but is commonly disrupted in older adults. Poor sleep can be detrimental to mental and physical health, including cognitive function. This study assessed the association between self‐reported short (<6 h) and long (>9 h) sleep duration and sleep fragmentation (3≥ nightly awakenings) in cognitive function. Methods: Cross‐sectional data from 8508 individuals enroled in the PROTECT study aged 50 and above formed the basis of the univariate linear regression analysis conducted on four cognitive outcomes assessing visuospatial episodic memory (VSEM), spatial working memory, verbal working memory (VWM), and verbal reasoning (VR). Results: Short (ß = −0.153, 95% CI [−0.258, −0.048], p = 0.004) and long sleep duration (ß = −0.459, 95% CI [−0.826, −0.091], p = 0.014) were significantly associated with poorer cognitive performance in VWM. Long sleep duration (ß = −2.986, 95% CI [−5.453, −0.518], p = 0.018) was associated with impaired VR. Short sleep (ß = −0.133, 95% CI [−0.196, −0.069], p = <0.001) and sleep fragmentation (ß = −0.043, 95% CI [−0.085, −0.001], p = 0.043) were associated with reduced VSEM. These associations remained significant when including other established risk factors for dementia and cognitive decline (e.g., depression, hypertension). Conclusions: Our findings suggest that short and long sleep durations and fragmented sleep, may be risk factors for a decline in cognitive processes such as working memory, VR and episodic memory thus might be potential targets for interventions to maintain cognitive health in ageing. Key points: This study assessed the association between self‐reported short (<6 h) and long (>9 h) sleep duration and sleep fragmentation (3 or more nightly awakenings) in cognitive function.Univariate linear regression analysis indicated that short and long sleep duration, and sleep fragmentation impaired cognitive processes such as working memory, verbal reasoning (VR) and episodic memory in individuals aged 50+, even when including other established risk factors for dementia and cognitive decline, such as low educational level, hearing loss, traumatic brain injury, hypertension, diabetes, alcohol consumption, obesity, smoking, depression, social isolation, and physical inactivity.Both sleep duration and sleep fragmentation are highlighted as potential risk factors for reduced cognitive function and might be a possible target for interventions to maintain cognitive health in ageing. [ABSTRACT FROM AUTHOR]

Background: Identifying predictors for general cognitive training (GCT) success in healthy older adults has many potential uses, including aiding intervention and improving individual dementia risk prediction, which are of high importance in health care. However, the factors that predict training improvements and the temporal course of predictors (eg, do the same prognostic factors predict training success after a short training period, such as 6 weeks, as well as after a longer training period, such as 6 months?) are largely unknown.Methods: Data (N = 4,184 healthy older individuals) from two arms (GCT vs. control) of a three-arm randomized controlled trial were reanalyzed to investigate predictors of GCT success in five cognitive tasks (grammatical reasoning, spatial working memory, digit vigilance, paired association learning, and verbal learning) at three time points (after 6 weeks, 3 months, and 6 months of training). Possible investigated predictors were sociodemographic variables, depressive symptoms, number of training sessions, cognitive baseline values, and all interaction terms (group*predictor).Results: Being female was predictive for improvement in grammatical reasoning at 6 weeks in the GCT group, and lower cognitive baseline scores were predictive for improvement in spatial working memory and verbal learning at 6 months.Conclusion: Our data indicate that predictors seem to change over time; remarkably, lower baseline performance at study entry is only a significant predictor at 6 months training. Possible reasons for these results are discussed in relation to the compensation hypothesis. J Am Geriatr Soc 68:-, 2020. [ABSTRACT FROM AUTHOR]

Objectives We test whether higher awareness of age-related gains (AARC-gains), lower awareness of age-related losses (AARC-losses), and more positive attitudes toward own aging (ATOA) are cross-sectionally related to more frequent social media use. We also investigate the strength and direction of the associations of AARC-gains, AARC-losses, and ATOA with social media use over 1 year, from before to after the onset of the coronavirus 2019 pandemic. Methods We used cross-sectional data from 8,320 individuals (mean age = 65.95 years; standard deviation = 7.01) and longitudinal data from a subsample of 4,454 individuals participating in the UK PROTECT study in 2019 and 2020. We used ordered regression models, linear regression models, and tests of interaction. Models were adjusted for age, sex, education, and employment. Results Higher AARC-gains and more positive ATOA, but not AARC-losses, were cross-sectionally associated with more frequent social media use. Social media use became more frequent at follow-up. In the longitudinal models controlling for baseline levels of the outcome variable, more frequent baseline social media use predicted increases in AARC-gains, whereas baseline AARC-gains did not significantly predict the frequency of social media use at follow-up. Baseline frequency of social media use did not significantly predict AARC-losses, nor ATOA at follow-up, whereas lower levels of AARC-losses and more positive ATOA predicted more frequent social media use at follow-up. Discussion Although effect sizes were small, decreasing negative views on aging may help increase the engagement of middle-aged and older people with social media. At the same time, fostering social media use could promote positive self-perceptions of aging. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study is to explore the current landscape of pain management in people with dementia living in care home settings. Pain is extremely common in this patient group, yet there is very limited guidance for healthcare professionals.Methods: Triangulation of stakeholder consultation and quality review of pain management guidance were performed. A review of existing pain management guidance was conducted using published quality criteria adapted for the field. Three focus group discussions were held with care home staff and two focus group discussions and an online survey with family carers. Data were subjected to thematic analysis to identify themes and sub-themes. Outcomes were reviewed by an expert panel, which gave recommendations.Results: Fifteen existing guidelines were identified, of which three were designed for use in dementia and none were tailored for care home settings. Thematic analysis revealed six major themes in current pain management in dementia: importance of person-centredness, current lack of pain awareness in staff, communication as a core element, disparities in staff responsibility and confidence, the need for consistency of care and current lack of staff training. In addition to the needs for practice, the expert panel identified promising pharmacological treatment candidates, which warrant clinical evaluation.Conclusions: The findings of this study clearly articulate a need for an evidence-based pain management programme for care homes, which is informed by stakeholder input and based within a conceptual framework for this setting. There are novel opportunities for clinical trials of alternative analgesics for use in this patient group. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We explored which factors are associated with subjective age (SA), i.e. feeling younger, the same as, or older than one's chronological age, and whether these factors differ between men and women and between two age sub-groups. Cross-sectional study using qualitative and quantitative data for 1457 individuals (mean age= 67.2 years). Participants reported how old they feel they are and provided comments in relation to their SA judgments. By using content analysis participants' comments were assigned to 13 categories, grouped into three higher-order categories (antecedents of age-related thoughts, mental processes, and issues when measuring subjective age). SA may result from the interaction between factors that increase or decrease age-related thoughts and mental processes that individuals use to interpret age-related changes. Chi-squared tests show that individuals reporting an older SA are more likely to experience significant negative changes and to engage in negative age-related thoughts than individuals reporting an age-congruent SA or a younger SA. Women experience a more negative SA and more age-salient events than men. Individuals reporting an older SA may benefit from interventions promoting adaptation to negative age-related changes. There is the need to eradicate negative societal views of older women. [ABSTRACT FROM AUTHOR]

Drug repositioning and repurposing can enhance traditional drug development efforts and could accelerate the identification of new treatments for individuals with Alzheimer disease (AD) dementia and mild cognitive impairment. Transcriptional profiling offers a new and highly efficient approach to the identification of novel candidates for repositioning and repurposing. In the future, novel AD transcriptional signatures from cells isolated at early stages of disease, or from human neurons or microglia that carry mutations that increase the risk of AD, might be used as probes to identify additional candidate drugs. Phase II trials assessing repurposed agents must consider the best target population for a specific candidate therapy as well as the mechanism of action of the treatment. In this Review, we highlight promising compounds to prioritize for clinical trials in individuals with AD, and discuss the value of Delphi consensus methodology and evidence-based reviews to inform this prioritization process. We also describe emerging work, focusing on the potential value of transcript signatures as a cost-effective approach to the identification of novel candidates for repositioning. [ABSTRACT FROM AUTHOR]

Objective: Establishing affordable lifestyle interventions that might preserve cognitive function in the aging population and subsequent generations is a growing area of research focus. Data from the PROTECT study has been utilised to examine whether number-puzzle use is related to cognitive function in older adults.Methods: Data from 19 078 healthy volunteers aged 50 to 93 years old enrolled on the online PROTECT study were evaluated for self-reported frequency of performing number puzzles. Two cognitive-test batteries were employed to assess core aspects of cognitive function including reasoning, focussed and sustained attention, information processing, executive function, working memory, and episodic memory. Analysis of covariance was used to establish the differences between the six frequency groups.Results: Highly statistically significant main effects of the frequency of performing number puzzles were seen on all 14 cognitive measures, with P values of less than 0.0004. Interestingly, participants who reported engaging in number puzzles more than once a day had superior cognitive performance on 10 core measures compared with all other frequency groups, although not all were statistically significant.Conclusions: This study has identified a close relationship between frequency of number-puzzle use and the quality of cognitive function in adults aged 50 to 93 years old. In order to determine the value of these findings as a potential intervention, further research should explore the type and difficulty of the number puzzles. These findings further contribute to the growing evidence that engaging in mentally stimulating activities could benefit the brain function of the ageing population. [ABSTRACT FROM AUTHOR]

Objective: The identification of modifiable lifestyle factors to preserve cognitive function in older individuals becomes increasingly of importance. This study examines whether word puzzle use is related to cognitive function in older adults.Methods: Cognitive data from 19 078 cognitively healthy individuals aged 50 to 93 years enrolled into the online PROTECT study were evaluated for self-reported frequency of performing word puzzles on a six-point scale, ranging from "more than once per day" to "never". Nine cognitive tests covered a range of domains including focussed and sustained attention, information processing, executive function, working memory, and episodic memory. Analyses of covariance were used to determine any differences between the six response groups.Results: Each of the 14 cognitive measures analysed showed highly statistically significant main effects of the frequency of performing word puzzles. For each measure, the group who never performed word puzzles performed most poorly, with the group who reported occasional puzzle use also performing more poorly than virtually every other group. Measures of speed provided the greatest discriminations, with a grammatical reasoning score differentiating the two highest frequency groups, performing word puzzles daily or more than once daily.Conclusions: The frequency of word puzzle use is directly related to cognitive function in adults aged 50 and over. Future work needs to determine whether engaging in such puzzles can favourably influence cognitive trajectory with age. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to establish the feasibility and initial effectiveness of training and support intervention for care staff to improve pain management in people with dementia living in care homes (PAIN-Dem).Methods: PAIN-Dem training was delivered to care staff from three care homes in South London, followed by intervention support and resources to encourage improved pain management by staff over 4 weeks. Feasibility was assessed through fidelity to intervention materials and qualitative approaches. Focus group discussions with staff explored the use of the PAIN-Dem intervention, and interviews were held with six residents and family carers. Pain was assessed in all residents at baseline, 3 and 4 weeks, and goal attainment scaling was assessed at 4 weeks.Results: Delivery of training was a key driver for success and feasibility of the PAIN-Dem intervention. Improvements in pain management behaviour and staff confidence were seen in homes where training was delivered in a care home setting across the care team with good manager buy-in. Family involvement in pain management was highlighted as an area for improvement. Goal attainment in residents was significantly improved across the cohort, although no significant change in pain was seen.Conclusions: This study shows good initial feasibility of the PAIN-Dem intervention and provides valuable insight into training and support paradigms that deliver successful learning and behaviour change. There is a need for a larger trial of PAIN-Dem to establish its impact on resident pain and quantifiable staff behaviour measures. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives Apathy is common, impactful, and difficult to manage in people with dementia. We evaluated the efficacy of nonpharmacological interventions, exercise, and social interaction, in combination with antipsychotic review, to reduce apathy in people with dementia living in nursing homes in a cluster randomized controlled trial (RCT). Methods Well-being and health for people with dementia (WHELD) program included a 2 × 2 × 2 factorial cluster RCT involving people with dementia living in 16 nursing homes in the United Kingdom. All homes received training in person-centered care, and were randomized to receive antipsychotic review, social interaction, and exercise, either alone or in combinations. Apathy was one of the secondary outcomes of the WHELD trial, and it was measured by the Neuropsychiatric Inventory–nursing home version at baseline and 9 months (n = 273). We used multilevel mixed effects linear regression models to assess the impact of the interventions on apathy. Results Prevalence of apathy was 44.0% (n = 120; 95% confidence interval [CI] 38.1%–49.9%) at baseline. Severity of apathy had significant positive correlations with dementia severity, neuropsychiatric symptoms, depressive symptoms, agitation, and the needs of the people with dementia ( P < .001). Antipsychotic review reduced antipsychotic use, but it significantly increased apathy (β = 5.37; SE = 0.91; P < . 001). However, antipsychotic review in combination with either social interaction (β = −5.84; SE = 1.15; P < . 001) or exercise (β = −7.54; SE = 0.93; P < . 001) significantly reduced apathy. Conclusions Antipsychotic review can play a significant role in improving apathy in people with dementia living in nursing homes, when combined with psychosocial interventions such as social interaction and exercise. Guidance must be adapted to reflect this subtlety in care. [ABSTRACT FROM AUTHOR]

Background: Vascular dementia is the second most common cause of dementia affecting over seven million people worldwide, yet there are no licensed treatments. There is an urgent need for a clinical trial in this patient group. Subcortical ischaemic vascular dementia is the most common variant of vascular dementia. This randomised trial will investigate whether use of calcium channel blockade with amlodipine, a commonly used agent, can provide the first evidence-based pharmacological treatment for subcortical ischaemic vascular dementia.Methods/design: This is a randomised controlled trial of calcium channel blockade with Amlodipine For the treatment oF subcortical ischaEmic vasCular demenTia (AFFECT) to test the hypothesis that treatment with amlodipine can improve outcomes for these patients in a phase IIb, multi-centre, double-blind, placebo-controlled randomised trial. The primary outcome is the change from baseline to 12 months in the Vascular Dementia Assessment Scale cognitive subscale (VADAS-cog). Secondary outcomes include cognitive function, executive function, clinical global impression of change, change in blood pressure, quantitative evaluation of lesion accrual based on magnetic resonance imaging (MRI), health-related quality of life, activities of daily living, non-cognitive dementia symptoms, care-giver burden and care-giver health-related quality of life, cost-effectiveness and institutionalisation. A total of 588 patients will be randomised in a 1:1 ratio to either amlodipine or placebo, recruited from sites across the UK and enrolled in the trial for 104 weeks.Discussion: There are no treatments licensed for vascular dementia. The most common subtype is subcortical ischaemic vascular dementia (SIVD). This study is designed to investigate whether amlodipine can produce benefits compared to placebo in established SIVD. It is estimated that the numbers of people with VaD and SIVD will increase globally in the future and the results of this study should inform important treatment decisions.Trial Registration: Current Controlled Trials ISRCTN31208535 . Registered on 7 March 2014. [ABSTRACT FROM AUTHOR]

Down's syndrome is the most common genetic cause of learning difficulties, and individuals with this condition represent the largest group of people with dementia under the age of 50 years. Genetic drivers result in a high frequency of Alzheimer's pathology in these individuals, evident from neuroimaging, biomarker, and neuropathological findings, and a high incidence of cognitive decline and dementia. However, cognitive assessment is challenging, and diagnostic methods have not been fully validated for use in these patients; hence, early diagnosis remains difficult. Evidence regarding the benefits of cholinesterase inhibitors and other therapeutic options to treat or delay progressive cognitive decline or dementia is very scarce. Despite close similarities with late-onset Alzheimer's disease, individuals with Down's syndrome respond differently to treatment, and a targeted approach to drug development is thus necessary. Genetic and preclinical studies offer opportunities for treatment development, and potential therapies have been identified using these approaches. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the impact of antipsychotic review, social interaction, and exercise, in conjunction with person-centered care, on antipsychotic use, agitation, and depression in people with dementia living in nursing homes.Method: A cluster-randomized factorial controlled trial with two replications was conducted in people with dementia in 16 U.K. nursing homes. All homes received training in person-centered care. Eight homes were randomly assigned to antipsychotic review, to a social interaction intervention, and to an exercise intervention for 9 months, with most homes assigned to more than one intervention. The primary outcome measures were antipsychotic use, agitation, and depression. Secondary outcome measures were overall neuropsychiatric symptoms and mortality.Results: Antipsychotic review significantly reduced antipsychotic use by 50% (odds ratio 0.17, 95% confidence interval [CI] 0.05 to 0.60). Antipsychotic review plus the social interaction intervention significantly reduced mortality (odds ratio 0.26, 95% CI 0.13 to 0.51) compared with the group receiving neither. The group receiving antipsychotic review but not the social intervention showed significantly worse outcome in neuropsychiatric symptoms compared with the group receiving neither (score difference +7.37, 95% CI 1.53 to 13.22). This detrimental impact was mitigated by concurrent delivery of the social intervention (-0.44, CI -4.39 to 3.52). The exercise intervention significantly improved neuropsychiatric symptoms (-3.59, 95% CI -7.08 to -0.09) but not depression (-1.21, CI -4.35 to 1.93). None of the interventions had a significant impact specifically on agitation.Conclusions: While reductions in antipsychotic use can be achieved by using a "real world" intervention, this may not be of benefit to people with dementia in the current climate of more judicious prescribing unless nonpharmacological interventions such as social interaction or exercise are provided in parallel. [ABSTRACT FROM AUTHOR]

Background Neuropsychiatric symptoms in Alzheimer disease (AD) cause significant distress and present a complex clinical challenge for treatment. Pharmacological treatment options are limited to antipsychotics, which carry extensive safety issues. There is emerging evidence to support the potential benefits of memantine, currently licensed for moderate to severe AD, in the prophylaxis of neuropsychiatric symptoms. Methods The MAIN-AD study is a double-blind randomized placebo-controlled withdrawal trial comparing memantine with antipsychotics for the treatment of neuropsychiatric symptoms over 24 weeks. A total of 199 people with probable AD living in care homes already receiving an antipsychotic were randomized to receive either memantine or to continue an antipsychotic. The primary outcomes were function (Bristol Activities of Daily Living Scale [BADLS]) and agitation (Cohen-Mansfield Agitation Inventory [CMAI]). Secondary outcomes were Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), and mortality. Results There was no significant difference between groups on the BADLS or CMAI. At 24 weeks, there was a nonsignificant adjusted difference in favor of memantine on the BADLS of 0.23 (95% CI –1.80–2.27; P = .82) and in favor of antipsychotic on the CMAI of 0.09 (95% CI –0.35–8.53; P = .07). Although there were no significant differences in total NPI, there were 5.01 (95% CI –1.68–11.70; P = .05) and 3.63 (95% CI –1.40–8.67; P = .16) point advantages favoring antipsychotics at weeks 12 and 24, respectively. In addition, in an exploratory analysis, individuals allocated to antipsychotics were significantly less likely to experience relapse of neuropsychiatric symptoms at all time points. The group receiving memantine had a nonsignificant 1.3-point advantage on the MMSE at 24 weeks. Discussion This study indicates no benefits for memantine in the long-term treatment and prophylaxis of clinically significant neuropsychiatric symptoms. The results did indicate some benefits for antipsychotic medications in reducing the relapse of neuropsychiatric symptoms, but this must be balanced against increased mortality risk. [ABSTRACT FROM AUTHOR]