-
British Journal of Sports Medicine Jun 2022Physical activity (PA) is associated with a decreased incidence of dementia, but much of the evidence comes from short follow-ups prone to reverse causation. This... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Physical activity (PA) is associated with a decreased incidence of dementia, but much of the evidence comes from short follow-ups prone to reverse causation. This meta-analysis investigates the effect of study length on the association.
DESIGN
A systematic review and meta-analysis. Pooled effect sizes, dose-response analysis and funnel plots were used to synthesise the results.
DATA SOURCES
CINAHL (last search 19 October 2021), PsycInfo, Scopus, PubMed, Web of Science (21 October 2021) and SPORTDiscus (26 October 2021).
ELIGIBILITY CRITERIA
Studies of adults with a prospective follow-up of at least 1 year, a valid cognitive measure or cohort in mid-life at baseline and an estimate of the association between baseline PA and follow-up all-cause dementia, Alzheimer's disease or vascular dementia were included (n=58).
RESULTS
PA was associated with a decreased risk of all-cause dementia (pooled relative risk 0.80, 95% CI 0.77 to 0.84, n=257 983), Alzheimer's disease (0.86, 95% CI 0.80 to 0.93, n=128 261) and vascular dementia (0.79, 95% CI 0.66 to 0.95, n=33 870), even in longer follow-ups (≥20 years) for all-cause dementia and Alzheimer's disease. Neither baseline age, follow-up length nor study quality significantly moderated the associations. Dose-response meta-analyses revealed significant linear, spline and quadratic trends within estimates for all-cause dementia incidence, but only a significant spline trend for Alzheimer's disease. Funnel plots showed possible publication bias for all-cause dementia and Alzheimer's disease.
CONCLUSION
PA was associated with lower incidence of all-cause dementia and Alzheimer's disease, even in longer follow-ups, supporting PA as a modifiable protective lifestyle factor, even after reducing the effects of reverse causation.
Topics: Alzheimer Disease; Dementia, Vascular; Disease Progression; Exercise; Humans; Prospective Studies; Protective Factors
PubMed: 35301183
DOI: 10.1136/bjsports-2021-104981 -
Molecular Psychiatry Oct 2021Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at the center of Alzheimer's disease (AD) pathophysiology. While the detailed molecular... (Review)
Review
Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at the center of Alzheimer's disease (AD) pathophysiology. While the detailed molecular mechanisms of the pathway and the spatial-temporal dynamics leading to synaptic failure, neurodegeneration, and clinical onset are still under intense investigation, the established biochemical alterations of the Aβ cycle remain the core biological hallmark of AD and are promising targets for the development of disease-modifying therapies. Here, we systematically review and update the vast state-of-the-art literature of Aβ science with evidence from basic research studies to human genetic and multi-modal biomarker investigations, which supports a crucial role of Aβ pathway dyshomeostasis in AD pathophysiological dynamics. We discuss the evidence highlighting a differentiated interaction of distinct Aβ species with other AD-related biological mechanisms, such as tau-mediated, neuroimmune and inflammatory changes, as well as a neurochemical imbalance. Through the lens of the latest development of multimodal in vivo biomarkers of AD, this cross-disciplinary review examines the compelling hypothesis- and data-driven rationale for Aβ-targeting therapeutic strategies in development for the early treatment of AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Humans; tau Proteins
PubMed: 34456336
DOI: 10.1038/s41380-021-01249-0 -
Journal of Sleep Research Aug 2021Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD... (Review)
Review
Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD dementia cases. However early intervention is needed in the course of AD at Mild Cognitive Impairment (MCI) or mild dementia stages to help prevent decline and maintain good quality of life. This systematic review aims to summarize evidence on sleep interventions in MCI and mild AD dementia. Seven databases were systematically searched for interventional studies where ≥ 75% of participants met diagnostic criteria for MCI/mild AD dementia, with a control group and validated sleep outcome measures. Studies with a majority of participants diagnosed with Moderate to Severe AD were excluded. After removal of duplicates, 22,133 references were returned in two separate searches (August 2019 and September 2020). 325 full papers were reviewed with 18 retained. Included papers reported 16 separate studies, total sample (n = 1,056), mean age 73.5 years. 13 interventions were represented: Cognitive Behavioural Therapy - Insomnia (CBT-I), A Multi-Component Group Based Therapy, A Structured Limbs Exercise Programme, Aromatherapy, Phase Locked Loop Acoustic Stimulation, Transcranial Stimulation, Suvorexant, Melatonin, Donepezil, Galantamine, Rivastigmine, Tetrahydroaminoacridine and Continuous Positive Airway Pressure (CPAP). Psychotherapeutic approaches utilising adapted CBT-I and a Structured Limbs Exercise Programme each achieved statistically significant improvements in the Pittsburgh Sleep Quality Index with one study reporting co-existent improved actigraphy variables. Suvorexant significantly increased Total Sleep Time and Sleep Efficiency whilst reducing Wake After Sleep Onset time. Transcranial Stimulation enhanced cortical slow oscillations and spindle power during daytime naps. Melatonin significantly reduced sleep latency in two small studies and sleep to wakefulness transitions in a small sample. CPAP demonstrated efficacy in participants with Obstructive Sleep Apnoea. Evidence to support other interventions was limited. Whilst new evidence is emerging, there remains a paucity of evidence for sleep interventions in MCI and mild AD highlighting a pressing need for high quality experimental studies exploring alternative sleep interventions.
Topics: Alzheimer Disease; Cognitive Dysfunction; Humans; Quality of Life; Sleep
PubMed: 33289311
DOI: 10.1111/jsr.13229 -
European Journal of Preventive... May 2022As the potential impact of statins on cognitive decline and dementia is still debated, we conducted a meta-analysis of observational studies to examine the effect of... (Meta-Analysis)
Meta-Analysis
AIMS
As the potential impact of statins on cognitive decline and dementia is still debated, we conducted a meta-analysis of observational studies to examine the effect of statin use on the risk of Alzheimer's disease (AD) and dementia.
METHODS AND RESULTS
PubMed, Cochrane, and EMBASE were searched since inception to January 2021. Inclusion criteria were: (i) cohort or case-control studies; (ii) statin users compared to non-users; and (iii) AD and/or dementia risk as outcome. Estimates from original studies were pooled using restricted maximum-likelihood random-effect model. Measure of effects were reported as odds ratio (OR) and 95% confidence intervals (CIs). In the pooled analyses, statins were associated with a decreased risk of dementia [36 studies, OR 0.80 (CI 0.75-0.86)] and of AD [21 studies, OR 0.68 (CI 0.56-0.81)]. In the stratified analysis by sex, no difference was observed in the risk reduction of dementia between men [OR 0.86 (CI 0.81-0.92)] and women [OR 0.86 (CI 0.81-0.92)]. Similar risks were observed for lipophilic and hydrophilic statins for both dementia and AD, while high-potency statins showed a 20% reduction of dementia risk compared with a 16% risk reduction associated with low-potency statins, suggesting a greater efficacy of the former, although a borderline statistical significance (P = 0.05) for the heterogeneity between estimates.
CONCLUSION
These results confirm the absence of a neurocognitive risk associated with statin treatment and suggest a potential favourable role of statins. Randomized clinical trials with an ad hoc design are needed to explore this potential neuroprotective effect.
Topics: Alzheimer Disease; Cognitive Dysfunction; Dementia; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Odds Ratio
PubMed: 34871380
DOI: 10.1093/eurjpc/zwab208 -
Alzheimer's Research & Therapy Mar 2023The use of music interventions as a non-pharmacological therapy to improve cognitive and behavioral symptoms in Alzheimer's disease (AD) patients has gained popularity... (Review)
Review
BACKGROUND
The use of music interventions as a non-pharmacological therapy to improve cognitive and behavioral symptoms in Alzheimer's disease (AD) patients has gained popularity in recent years, but the evidence for their effectiveness remains inconsistent.
OBJECTIVES
To summarize the evidence of the effect of music therapy (alone or in combination with pharmacological therapies) on cognitive functions in AD patients compared to those without the intervention.
METHODS
A systematic literature search was performed in PubMed, Cochrane library, and HINARI for papers published from 1 January 2012 to 25 June 2022. All randomized controlled trials that compared music therapy with standard care or other non-musical intervention and evaluation of cognitive functions are included. Cognitive outcomes included: global cognition, memory, language, speed of information processing, verbal fluency, and attention. Quality assessment and narrative synthesis of the studies were performed.
RESULTS
A total of 8 studies out of 144 met the inclusion criteria (689 participants, mean age range 60.47-87.1). Of the total studies, 4 were conducted in Europe (2 in France, 2 in Spain), 3 in Asia (2 in China, 1 in Japan), and 1 in the USA. Quality assessment of the retrieved studies revealed that 6 out of 8 studies were of high quality. The results showed that compared to different control groups, there is an improvement in cognitive functions after music therapy application. A greater effect was shown when patients are involved in the music making when using active music intervention (AMI).
CONCLUSION
The results of this review highlight the potential benefits of music therapy as a complementary treatment option for individuals with AD and the importance of continued investigation in this field. More research is needed to fully understand the effects of music therapy, to determine the optimal intervention strategy, and to assess the long-term effects of music therapy on cognitive functions.
Topics: Aged; Aged, 80 and over; Humans; Middle Aged; Alzheimer Disease; Cognition; Music; Music Therapy; Randomized Controlled Trials as Topic
PubMed: 36973733
DOI: 10.1186/s13195-023-01214-9 -
Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia.The Cochrane Database of Systematic... Dec 2021Typical and atypical antipsychotics are widely used to treat agitation and psychosis in dementia. However, whether or not they are beneficial is uncertain. Some trials... (Review)
Review
BACKGROUND
Typical and atypical antipsychotics are widely used to treat agitation and psychosis in dementia. However, whether or not they are beneficial is uncertain. Some trials have yielded negative results and effectiveness may be outweighed by harms.
OBJECTIVES
To assess the efficacy and safety of antipsychotics for the treatment of agitation and psychosis in people with Alzheimer's disease and vascular dementia.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (Ovid Sp), Embase (Ovid SP), PsycINFO (Ovid SP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov and the World Health Organization's meta-register, and the International Clinical Trials Registry Portal on 7 January 2021. Two review authors independently screened the title and abstract of the hits, and two review authors assessed the full text of studies that got through this screening.
SELECTION CRITERIA
We included randomised, placebo-controlled, parallel-arm trials comparing the effects of antipsychotics and placebo for the treatment of agitation or psychosis in people with dementia due to Alzheimer's disease or vascular dementia, or both, irrespective of age, severity of cognitive impairment, and setting. (The majority of) participants had to have clinically significant agitation (including aggression) or psychosis or both at baseline. We excluded studies about antipsychotics that are no longer available in the USA or EU, or that are used for emergency short-term sedation. We also excluded head-to-head trials and antipsychotic withdrawal trials.
DATA COLLECTION AND ANALYSIS
The primary outcomes were (1) reduction in agitation or psychosis in participants with agitation or psychosis, respectively at baseline, and (2) the number of participants with adverse events: somnolence, extrapyramidal symptoms, any adverse event, any serious adverse event (SAE), and death. Two review authors independently extracted the necessary data and assessed risk of bias with the Cochrane risk of bias tool. We calculated the pooled effect on agitation and psychosis for typical and atypical antipsychotics separately, and the pooled risk of adverse effects independent of the target symptom (agitation or psychosis). We used RevMan Web for the analyses.
MAIN RESULTS
The search yielded 8233 separate hits. After assessing the full-text of 35 studies, we included 24 trials that met the eligibility criteria. Six trials tested a typical antipsychotic, four for agitation and two for psychosis. Twenty trials tested an atypical antipsychotic, eight for agitation and 12 for psychosis. Two trials tested both drug types. Seventeen of 26 comparisons were performed in patients with Alzheimer's disease specifically. The other nine comparisons also included patients with vascular dementia or mixed dementia. Together, the studies included 6090 participants (12 to 652 per study). The trials were performed in institutionalised, hospitalised and community-dwelling patients, or a combination of those. For typical antipsychotics (e.g. haloperidol, thiothixene), we are uncertain whether these drugs improve agitation compared with placebo (standardised mean difference (SMD) -0.36, 95% confidence interval (CI) -0.57 to -0.15, 4 studies, n = 361); very low-certainty evidence, but typical antipsychotics may improve psychosis slightly (SMD -0.29, 95% CI -0.55 to -0.03, 2studies, n= 240; low-certainty evidence) compared with placebo. These drugs probably increase the risk of somnolence (risk ratio (RR) 2.62, 95% CI 1.51 to 4.56, 3 studies, n = 466; moderate-certainty evidence) and increase extrapyramidal symptoms (RR 2.26, 95% CI 1.58 to 3.23, 3 studies, n = 467; high-certainty) evidence. There was no evidence regarding the risk of any adverse event. The risks of SAEs (RR 1.32, 95% CI 0.65 to 2.66, 1 study, n = 193) and death (RR 1.46, 95% CI 0.54 to 4.00, 6 studies, n = 578) may be increased slightly, but these estimates were very imprecise, and the certainty was low. The effect estimates for haloperidol from five trials were in line with those of the drug class. Atypical antipsychotics (e.g. risperidone, olanzapine, aripiprazole, quetiapine) probably reduce agitation slightly (SMD -0.21, 95% CI -0.30 to -0.12, 7 studies, n = 1971; moderate-certainty evidence), but probably have a negligible effect on psychosis (SMD -0.11, 95% CI -0.18 to -0.03, 12 studies, n = 3364; moderate-certainty evidence). These drugs increase the risk of somnolence (RR 1.93, 95% CI 1.57 to 2.39, 13 studies, n - 3878; high-certainty evidence) and are probably also associated with slightly increased risk of extrapyramidal symptoms (RR 1.39, 95% CI 1.14 to 1.68, 15 studies, n = 4180; moderate-certainty evidence), serious adverse events (RR 1.32, 95% CI 1.09 to 1.61, 15 studies, n= 4316; moderate-certainty evidence) and death (RR 1.36, 95% CI 0.90 to 2.05, 17 studies, n= 5032; moderate-certainty evidence), although the latter estimate was imprecise. The drugs probably have a negligible effect on the risk of any adverse event (RR 1.05, 95% CI 1.02 to 1.09, 11 studies, n = 2785; moderate-certainty evidence). The findings from seven trials for risperidone were in line with those for the drug class.
AUTHORS' CONCLUSIONS
There is some evidence that typical antipsychotics might decrease agitation and psychosis slightly in patients with dementia. Atypical antipsychotics reduce agitation in dementia slightly, but their effect on psychosis in dementia is negligible. The apparent effectiveness of the drugs seen in daily practice may be explained by a favourable natural course of the symptoms, as observed in the placebo groups. Both drug classes increase the risk of somnolence and other adverse events. If antipsychotics are considered for sedation in patients with severe and dangerous symptoms, this should be discussed openly with the patient and legal representative.
Topics: Alzheimer Disease; Antipsychotic Agents; Dementia, Vascular; Humans; Psychotic Disorders; Randomized Controlled Trials as Topic; Risperidone
PubMed: 34918337
DOI: 10.1002/14651858.CD013304.pub2 -
Ageing Research Reviews Dec 2021To assess the potential multi-domain benefits of exercise interventions on patients with Alzheimer's disease (AD), as well as to determine the specific effects of... (Meta-Analysis)
Meta-Analysis Review
AIMS
To assess the potential multi-domain benefits of exercise interventions on patients with Alzheimer's disease (AD), as well as to determine the specific effects of different exercise modalities (aerobic, strength, or combined training).
METHODS
A systematic search was conducted in PubMed and Web of Science until March 2021 for randomized controlled trials assessing the effect of exercise interventions (compared with no exercise) on patients with AD. Outcomes included cognitive function (mini-mental state examination [MMSE] test), physical function (e.g., 6-minute walking test [6MWT]), functional independence (Barthel index), and neuropsychiatric symptoms (Neuropsychiatric Inventory [NPI]). A random-effects meta-analysis was conducted.
RESULTS
28 studies (total n = 1337 participants, average age 79-90 years) were included in the systematic review, of which 21 could be meta-analyzed. Although considerable heterogeneity was found, exercise interventions induced several significant benefits, including in Barthel index (n = 147 patients, mean difference [MD]=8.36 points, 95% confidence interval [CI]=0.63-16.09), 6MWT (n = 369, MD=84 m, 95% CI=44-133)), and NPI (n = 263, MD=-4.4 points, 95% CI=-8.42 to -0.38). Benefits were also found in the MMSE test, albeit significance was only reached for aerobic exercise (n = 187, MD=2.31 points, 95% CI 0.45-4.27).
CONCLUSIONS
Exercise interventions appear to exert multi-domain benefits in patients with AD.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognition; Exercise; Exercise Therapy; Humans; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 34601135
DOI: 10.1016/j.arr.2021.101479 -
International Journal of Environmental... Sep 2021The hypothesis of an infectious connection from the oro-pharyngeal sphere to the brain underlines the interest in analyzing the link between periodontal disease and... (Review)
Review
The hypothesis of an infectious connection from the oro-pharyngeal sphere to the brain underlines the interest in analyzing the link between periodontal disease and Alzheimer's disease. The aim of this systematic review was to examine the link between Alzheimer's disease and periodontal disease in patients aged 65 and over. Databases (PubMed (MEDLINE), the Cochrane Library, and Embase) were analyzed for relevant references up to 21 June 2021. The authors independently selected the studies and extracted the data. The quality of included studies was checked using the National Institutes of Health's quality assessment tools. Five studies were included. The selected studies described in their results an increase in in Alzheimer's disease patients (adjusted = 0.02), and its incidence was linked to and (adjusted HR = 1.22 (1.04-1.43), = 0.012) as well as (crude HR = 2.0 (1.1-3.8)). The presence of periodontitis at baseline was associated with a six-fold increase in the rate of cognitive decline over a 6-month follow-up period (ADAS-Cog mean change = 2.9 ± 6.6). The current review suggests an association between periodontal disease and Alzheimer's disease. The treatment of periodontal disease could be a way to explore Alzheimer's disease prevention.
Topics: Alzheimer Disease; Brain; Cognitive Dysfunction; Humans; Periodontal Diseases; Periodontitis
PubMed: 34501899
DOI: 10.3390/ijerph18179312 -
Journal of Sleep Research Oct 2022Sleep apnea (SA) is potentially a modifiable risk factor for dementia. However, its associations to specific aetiologies of dementia remain uncertain. A systematic... (Meta-Analysis)
Meta-Analysis
Sleep apnea (SA) is potentially a modifiable risk factor for dementia. However, its associations to specific aetiologies of dementia remain uncertain. A systematic review and meta-analysis of cohort studies investigating the association between sleep apnea and specific aetiologies of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), vascular dementia (VaD), and frontotemporal dementia (FTD) was performed. The use of biomarkers to support clinical diagnoses in eligible studies was collected. Eleven studies were included, comprising 1,333,424 patients. Patients with sleep apnea had an increased risk of developing any type of neurocognitive disorder (HR: 1.43 [95% CI 1.26-1.62]), Alzheimer's disease (HR: 1.28 [95% CI 1.16-1.41]), and Parkinson's disease (HR: 1.54 [95% CI 1.30-1.84]). No statistically significant association was found for vascular dementia. One study reported a two-fold increased risk for Lewy body dementia (HR: 2.06 [95% CI 1.45-2.91]). No studies investigated the risk for frontotemporal dementia and none of the studies reported results pertaining to biomarkers. Sleep apnea is associated with a significantly increased risk of dementia, particularly for Alzheimer's disease and Parkinson's disease, but not for vascular dementia. Future studies should look at the impact of sleep apnea on specific dementia biomarkers.
Topics: Alzheimer Disease; Biomarkers; Dementia, Vascular; Frontotemporal Dementia; Humans; Lewy Body Disease; Parkinson Disease; Sleep Apnea Syndromes
PubMed: 35366021
DOI: 10.1111/jsr.13589 -
Neuropsychology Review Jun 2021Cognitive reserve (CR) may reduce the risk of dementia. We summarized the effect of CR on progression to mild cognitive impairment (MCI) or dementia in studies... (Meta-Analysis)
Meta-Analysis Review
Cognitive reserve (CR) may reduce the risk of dementia. We summarized the effect of CR on progression to mild cognitive impairment (MCI) or dementia in studies accounting for Alzheimer's disease (AD)-related structural pathology and biomarkers. Literature search was conducted in Web of Science, PubMed, Embase, and PsycINFO. Relevant articles were longitudinal, in English, and investigating MCI or dementia incidence. Meta-analysis was conducted on nine articles, four measuring CR as cognitive residual of neuropathology and five as composite psychosocial proxies (e.g., education). High CR was related to a 47% reduced relative risk of MCI or dementia (pooled-hazard ratio: 0.53 [0.35, 0.81]), with residual-based CR reducing risk by 62% and proxy-based CR by 48%. CR protects against MCI and dementia progression above and beyond the effect of AD-related structural pathology and biomarkers. The finding that proxy-based measures of CR rivaled residual-based measures in terms of effect on dementia incidence underscores the importance of early- and mid-life factors in preventing dementia later.
Topics: Alzheimer Disease; Cognitive Dysfunction; Cognitive Reserve; Disease Progression; Humans
PubMed: 33415533
DOI: 10.1007/s11065-021-09478-4