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BACKGROUND: Alcohol use is associated with a wide spectrum of neurological disorders, including cognitive dysfunction and dementia. Likewise, the high prevalence of cognitive dysfunction and dementia specifies the urgent need to identify modifiable risk factors. Because findings on alcohol and cognitive dysfunction and dementia have been inconsistent, the present dose-response meta-analysis of cohort and case control studies was conducted to evaluate the available evidence. METHOD AND MATERIALS: A systematic search was conducted on PubMed/MEDLINE, Scopus, Embase, and PsychInfo databases and Google Scholar up to April, 2023. In the dose-response meta-analysis, a restricted cubic spline regression model was conducted to evaluate a possible non-linear relation between alcohol intake and the outcomes. Random-effects model was used to perform the meta-analysis and evaluate heterogeneity. Egger's test and a funnel plot were used to assess small study effects. Subgroup analyses were carried out to explore possible sources of heterogeneity. RESULTS: Seventeen eligible studies comprising 80,680 total persons with 4929 cases for dementia and 13,530 total persons with 1579 cases for cognitive dysfunction were included for dose-response analysis. When compared to the reference group of 0 g/day of alcohol intake, the dose-response meta-analysis revealed a significant non-linear (J-shaped) association between alcohol intake and the risk of each of cognitive dysfunction, (lower dose range: 1-30.5 g/day, RR: 0.97; 95 % CI 0.95-0.99; higher dose range: >30.5 g/day, RR: 1.07; 95 % CI 1.01-1.15) and dementia (lower dose range: 1-17.5 g/day, RR: 0.92; 95 % CI 0.88-0.96, higher dose range: >17.5 g/day, RR: 1.23; 95 % CI 1.09-1.35). The lowest risk was achieved at approximately 30 g/day of alcohol for cognitive dysfunction and 15 g/day for dementia. The J-shape association remained with subgroups defined by age (≤65; >65 years) or study duration (<10; ≥10 years) for dementia, and within age >65 and duration <10 years for cognitive dysfunction. CONCLUSION: We observed a J-shape association between alcohol consumption and both cognitive dysfunction and dementia, with light-to-moderate alcohol intake being associated with a reduced risk in adults. Further studies are needed to clarify more specifically the association between alcohol consumption and six domains of cognitive dysfunction based on diagnostic and statistical manual of mental disorders (DSM) criteria.

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BACKGROUND: Mobile health (mHealth) have significantly advanced evaluating neurocognitive functions; but, few reports have documented whether they validate neurocognitive impairments as well as paper-and-pencil neuropsychological tests. OBJECTIVE: To meta-analyze the correlation between mobile applications for neuropsychological tests and validated paper-and-pencil neuropsychological tests for evaluating neurocognitive impairments. METHOD: We used PubMed, Embase, Cochrane, Web of Science, and IEEE Explorer through January 2020 to identify studies that compared mobile applications for neuropsychological tests vs. paper-and-pencil neurophysiological tests. We used random-effects models via the DerSimonian and Laird method to extract pooled Pearson's correlation coefficients and we stratified by study design. RESULT: Nine out of 4639 screened articles (one RCT and eight prospective longitudinal case series) were included. For the observational studies, there was a statistically significant strong and direct correlation between mobile applications for neuropsychological test scores and validated paper-and-pencil neuropsychological assessment scores (r = 0.70; 95% CI 0.59, 0.79; I2 = 74.5%; p- heterogeneity <0.001). Stronger results were seen for the RCT (r = 0.92; 95% CI 0.77, 0.97). CONCLUSION: This meta-analysis showed a statistically significant correlation between mobile applications and the validated paper-and-pencil neuropsychological assessments analyzed for the evaluation of neurocognitive impairments.

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Importance: Atypical antipsychotics offer modest effectiveness compared with placebo but with serious safety risks, including a boxed warning for the risk of death in the treatment of behavioral and psychological symptoms of dementia (BPSD). Their comparative effectiveness and safety are not fully known. Objective: To assess the relative benefits and safety of atypical antipsychotics in the treatment of BPSD shown in randomized clinical trials using network meta-analysis. Data Sources: PubMed/MEDLINE, Embase, PsychINFO, and Cochrane Library were searched from their inception until May 31, 2018. Key terms included dementia and atypical antipsychotics. Study Selection: Randomized clinical trials comparing any atypical antipsychotic with another atypical antipsychotic or with placebo were included in the analysis. Data Extraction and Synthesis: Two independent reviewers used a standardized data extraction and quality assessment form. Random-effects network meta-analyses were performed. Effect sizes were reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with 95% CIs. In addition to ORs, the surface under the cumulative ranking curve (SUCRA) was ascertained, which represents the percentage of the effectiveness or safety for each treatment compared with a hypothetical treatment that would be ranked first without uncertainty. Main Outcomes and Measures: The primary effectiveness outcome assessed was the Neuropsychiatric Inventory (NPI); secondary effectiveness outcomes were the Brief Psychiatric Rating Scale (BPRS) and Cohen-Mansfield Agitation Inventory (CMAI). The primary safety outcomes were death and cerebrovascular adverse events (CVAEs). Secondary safety outcomes were extrapyramidal signs/symptoms; somnolence/sedation; falls, fracture, or injury; and urinary tract infection/incontinence. Results: Seventeen studies (5373 patients) were included. The mean (SD) age of all participants was 80.8 (3.1) years, and most were women (3748 [69.8%]). Compared with placebo, aripiprazole was associated with improvement in outcomes on the NPI (SMD, -0.17; 95% CI, -0.31 to -0.02), BPRS (SMD, -0.20; 95% CI, -0.35 to -0.05), and CMAI (SMD, -0.30; 95% CI, -0.55 to -0.05); quetiapine was associated with improvement in outcomes on the BPRS (SMD, -0.24; 95% CI, -0.46 to -0.01), and risperidone was associated with improvement in outcomes on the CMAI (SMD, -0.26; 95% CI, -0.37 to -0.15). Differences between atypical antipsychotics were not significant for effectiveness, death, or CVAE. Compared with placebo, risperidone (OR, 3.85; 95% CI, 1.55-9.55) and olanzapine (OR, 4.28; 95% CI, 1.26-14.56) were associated with increased risk of CVAEs. The SUCRA estimated relative ranking of treatments suggested that aripiprazole might be the most effective and safe atypical antipsychotic and that olanzapine provides the least benefit overall; however, these results should be interpreted with caution where point estimates (OR and SMD) show that there is no statistically significant difference. Conclusions and Relevance: This network meta-analysis supports the existence of a trade-off between the effectiveness and safety of atypical antipsychotics in the treatment of BPSD and confirms that a single most effective and safe treatment option does not exist. Clinicians should individualize the assessment of safety risks against expected benefits when prescribing these medications to patients with dementia.

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BACKGROUND: Cognitive impairment following transsphenoidal surgery (TSS) among patients with pituitary tumors has been intermittently reported and is not well established. We performed a systematic review to summarize the impact of TSS on cognitive function. METHODS: We conducted a systematic search of the literature using the PubMed, Cochrane, and Embase databases through October 2014. Studies were selected if they reported cognitive status after surgery and included at least 10 adult patients with pituitary tumors undergoing either endoscopic or microscopic TSS. RESULTS: After removing 69 duplicates, 758 articles were identified, of which 24 were selected for full text review after screening titles and abstracts. After reviewing full texts, nine studies with a combined total of 682 patients were included in the final analysis. Eight studies were cross-sectional and one was longitudinal. These studies used a wide variety of neurocognitive tests to assess memory, attention and executive function post-operatively. Of the eight studies, six reported impairments in verbal and non-verbal memory post-operatively, while others found no association related to memory, and some reported an improvement in episodic, verbal, or logical memory. While four studies found an impaired association between TSS and attention or executive function, another four studies did not. CONCLUSION: The current literature on cognitive impairments after TSS is limited and inconsistent. This review demonstrates that patients undergoing TSS may experience a variety of effects on executive function and memory post-operatively, but changes in verbal memory are most common.

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PURPOSE: To study the association between blood pressure and neuropsychological test performance in healthy postmenopausal women. METHODS: Data from 88 healthy postmenopausal women aged 46-73 years, who were not experiencing hot flashes, and who had participated in a prior drug trial, were analyzed to find whether baseline blood pressure was associated with impaired performance on neuropsychological testing done at 3 follow-up visits separated by 4 weeks. Factor analysis was used to reduce the dimensions of neuropsychological test performance. Mixed linear modeling was used to evaluate the association between baseline blood pressure and repeatedly measured neuropsychological test performance at follow-up in a complete case analysis (n=53). In a sensitivity analysis (n=88), multiple-imputation using the Markov Chain Monte Carlo method was used to account for missing data (blood pressure results) for some visits. RESULTS: The variables recording neuropsychological test performance were reduced to two main factors (Factor 1=selective attention; Factor 2=complex processing). In the complete case analysis, the association between a 20-mmHg increase in diastolic blood pressure and Factor 1 remained statistically significant after adjusting for potential confounders, before adjusting for systolic blood pressure (slope=0.60; 95%CI=0.04,1.16), and after adjusting for systolic blood pressure (slope=0.76; 95%CI=0.06, 1.47). The positive slopes indicated an increase in the time spent performing a given task (i.e., a decrease in neuropsychological test performance). No other significant associations were found between systolic blood pressure and either factor. The results did not materially change after applying the multiple-imputation method. CONCLUSIONS: An increase in diastolic blood pressure was associated with a decrease in neuropsychological test performance among older healthy postmenopausal women experiencing hot flashes.

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PURPOSE: To explain the controversy about whether midlife women who self-report hot flashes have relatively increased affective symptoms, poor cognitive performance or worse sleep. METHODS: Retrospective data from 88 women seeking relief from bothersome day and night hot flashes were submitted to mixed linear regression modeling to find if estimated hot flashes, as measured by Women's Health Questionnaire (WHQ) items, or diary-documented hot flashes recorded daily, were associated with each other, or with affective, cognitive or sleep measures. RESULTS: Subjects averaged 6.3 daytime diary-documented hot flashes and 2.4 nighttime diary-documented hot flashes per 24h. Confounder-controlled diary-documented hot flashes but not estimated hot flashes were associated with increased Leeds anxiety scores (F=4.9; t=2.8; p=0.01) and Leeds depression scores (3.4; 2.5; 0.02), decreased Stroop Color-Word test performance (9.4; 3.5; 0.001), increased subjective sleep disturbance (effect size=0.83) and increased objective sleep disturbance (effect size=0.35). Hot flash effects were small to moderate in size. Univariate but not multivariate analyses revealed that all hot flash measures were associated with all affect measures. Different measures of hot flashes associated differently with affect, cognition and sleep. Only nighttime diary-document hot flash consistently correlated with any affect measures in multivariate analyses. CONCLUSIONS: The use of differing measures for hot flashes, affect, cognition and sleep may account for the continually reported inconsistencies in menopause study outcomes. This problem impedes forging a consensus on whether hot flashes correlate with neuropsychological symptoms.

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The objective of the study was to evaluate relationships between sleep habits and depressive symptoms. Pilot study data were collected about sleep schedules, related factors and depression in female college students to find whether their sleep schedules correlate with affective symptoms. In the subsequent main study, similar information was collected under more controlled conditions. Depression was measured using the CES-D (Center for Epidemiologic Studies Depression Scale) and HAM-D-3 (modified Hamilton Depression Rating Scale). Response rates were 31.3% of eligible students for the pilot survey and 71.6% for the main study. Both studies showed that about 20% of students reported weekday sleep debts of greater than 2 h and about 28% reported significantly greater sleep debt and had significantly higher depression scores (P<0.0001) than other students. Melancholic symptoms indicated by high CES-D scores (>24), were observed in 24% of students. Sleep problems explained 13% of the variance for both the CESD scale and the HAM-D-3 scale. Among female college students, those who report a sleep debt of at least 2 h or significant daytime sleepiness have a higher risk of reporting melancholic symptoms than others.

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