Alcohol consumption in relation to cognitive dysfunction and dementia: A systematic review and dose-response meta-analysis of prospective cohort studies.

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 prospective cohort 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 4,929 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 0g/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: 1-30.5g/day, RR: 0.97; 95% CI 0.95-0.99; higher dose range: >30.5g/day, RR: 1.07; 95% CI 1.01-1.15) and dementia (lower dose range: 1-17.5g/day, RR: 0.92; 95% CI 0.88-0.96, higher dose range: >17.5g/day, RR: 1.23; 95% CI 1.09-1.35). The lowest risk was achieved at approximately 30g/day of alcohol for cognitive dysfunction and 15g/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.

Mobile health and neurocognitive domains evaluation through smartphones: A meta-analysis.

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.

Assessment of Reported Comparative Effectiveness and Safety of Atypical Antipsychotics in the Treatment of Behavioral and Psychological Symptoms of Dementia: A Network Meta-analysis.

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.

The impact of transsphenoidal surgery on neurocognitive function: A systematic review.

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.

Self-reported sleep in postmenopausal women.

OBJECTIVE: We aimed to find how self-reported sleep (measured by the St. Mary's Hospital Sleep Questionnaire) in postmenopausal women having hot flash activity was related to objective sleep (actigraphy), psychological and somatic symptoms [Women's Health Questionnaire (WHQ)], and cognitive test performance (computerized tests). A secondary aim was to find if self-reported sleep showed expected correlations with hyperarousal (Hyperarousal Scale). DESIGN: Drug trial baseline data from 88 healthy, postmenopausal women were retrospectively analyzed. Multivariate regression was used to adjust for confounder variables and test whether differences in self-reported sleep measures were systematically associated with differences in objective sleep, WHQ symptom measures, or cognitive test performance scores. RESULTS: Increased self-report scores for low sleep quality were associated with an increased risk of WHQ symptoms and reduced cognitive test performance. Self-reported sleep measures showed little correlation with their analogous objective measures. Self-reported low sleep quality proved most closely associated with the WHQ symptoms of tiredness, clumsiness, and difficulty concentrating. Women whose self-reported sleep-onset latency times were longer than the median overestimated their objective sleep onset time by 30 min, whereas the other women underestimated theirs by 15 min (P < 0.0001). Women whose self-reported total sleep was longer or shorter than the median, respectively, underestimated objective sleep times by 9 and 71 min (P < 0.0001). High hyperarousal scores were associated with underestimations of objective sleep. CONCLUSION: Self-reports of lower sleep quality were associated with increased WHQ psychological and somatic symptom measures and decreased cognitive test performance more than with differences in objective sleep. Self-reported trouble sleeping may signal problems independent from objectively low sleep quality, such as subjective distress or diminished cognitive function.

Comparative efficacy of zolpidem and temazepam in transient insomnia.

This study compared hypnotic effects of zolpidem 10 mg, temazepam 15 mg and placebo in healthy adults. Two factors expected to promote insomnia, the 'first night effect' and a 2-hour phase advance, were combined in a single night laboratory-based double-blinded protocol. This was a multi-center study, with data collected in 13 sleep laboratories. Subjects with normal sleep histories and without prior sleep laboratory experience were randomly assigned to treatment groups. Medications were administered 15 min before lights out, with polysomnographic monitoring for 7.5 h. Subjective questionnaires and performance tests, digit symbol substitution test (DSST) and symbol copying test (SCT), were administered at study entry and after arising. 630 subjects completed the study and provided data analyzed using repeated measures ANOVAs. Neither agent significantly reduced objective sleep latency relative to placebo. Zolpidem reduced awakenings and wake after sleep onset (WASO); temazepam did not. Both agents improved sleep efficiency and most subjective sleep measures relative to placebo, with zolpidem superior for five of six subjective outcome measures compared to temazepam. SCT, morning sleepiness and morning concentration were not altered by any treatment. Zolpidem significantly reduced morning DSST performance; temazepam did not. Zolpidem 10 mg provided greater subjective hypnotic efficacy than temazepam 15 mg in this model of transient insomnia, with reduced polysomnographic awakenings and WASO. Impairment of DSST was seen with zolpidem but not temazepam. Copyright 2001 John Wiley & Sons, Ltd.

Electroconvulsive Therapy in Patients at High Risk for Physical Complications.

Nineteen patients had unrelieved incapacitating or life-threatening conditions likely remediable with electroconvulsive therapy (ECT). They also had coexisting medical conditions originally judged to preclude ECT because it risked unacceptable complications. ECT was administered with attempts to prevent complications, although some procedures were canceled for medical reasons. Fourteen of 19 patients completed their course of ECT; one patient died. Sixteen of 19 patients returned to baseline functioning and were discharged. Judicious attempts to treat such high-risk patients with ECT yield therapeutic gains.