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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 Neurology, Neurosurgery, and... Nov 2020Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention.
METHODS
Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised.
RESULTS
A total of 44 676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B).
INTERPRETATION
Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.
Topics: Alzheimer Disease; Antihypertensive Agents; Cognition; Craniocerebral Trauma; Depression; Diabetes Mellitus; Education; Evidence-Based Medicine; Exercise; Humans; Hyperhomocysteinemia; Hypertension; Hypotension, Orthostatic; Life Style; Obesity; Observational Studies as Topic; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Stress, Psychological
PubMed: 32690803
DOI: 10.1136/jnnp-2019-321913 -
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 -
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 -
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 -
Ageing Research Reviews Aug 2022Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique. When stimulation is applied over the primary motor cortex and coupled with... (Meta-Analysis)
Meta-Analysis Review
Cortical excitability and plasticity in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis of transcranial magnetic stimulation studies.
BACKGROUND
Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique. When stimulation is applied over the primary motor cortex and coupled with electromyography measures, TMS can probe functions of cortical excitability and plasticity in vivo. The purpose of this meta-analysis is to evaluate the utility of TMS-derived measures for differentiating patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) from cognitively normal older adults (CN).
METHODS
Databases searched included PubMed, Embase, APA PsycInfo, Medline, and CINAHL Plus from inception to July 2021.
RESULTS
Sixty-one studies with a total of 2728 participants (1454 patients with AD, 163 patients with MCI, and 1111 CN) were included. Patients with AD showed significantly higher cortical excitability, lower cortical inhibition, and impaired cortical plasticity compared to the CN cohorts. Patients with MCI exhibited increased cortical excitability and reduced plasticity compared to the CN cohort. Additionally, lower cognitive performance was significantly associated with higher cortical excitability and lower inhibition. No seizure events due to TMS were reported, and the mild adverse response rate is approximately 3/1000 (i.e., 9/2728).
CONCLUSIONS
Findings of our meta-analysis demonstrate the potential of using TMS-derived cortical excitability and plasticity measures as diagnostic biomarkers and therapeutic targets for AD and MCI.
Topics: Aged; Alzheimer Disease; Cognitive Dysfunction; Cortical Excitability; Humans; Neuronal Plasticity; Transcranial Magnetic Stimulation
PubMed: 35680080
DOI: 10.1016/j.arr.2022.101660 -
International Journal of Environmental... Jul 2022Aging is characterized by changes in the structure and quality of sleep. When the alterations in sleep become substantial, they can generate or accelerate cognitive... (Review)
Review
Aging is characterized by changes in the structure and quality of sleep. When the alterations in sleep become substantial, they can generate or accelerate cognitive decline, even in the absence of overt pathology. In fact, impaired sleep represents one of the earliest symptoms of Alzheimer's disease (AD). This systematic review aimed to analyze the studies on sleep quality in aging, also considering mild cognitive impairment (MCI) and AD. The review process was conducted according to the PRISMA statement. A total of 71 studies were included, and the whole sample had a mean age that ranged from 58.3 to 93.7 years (62.8-93.7 healthy participants and 61.8-86.7 pathological populations). Of these selected studies, 33 adopt subjective measurements, 31 adopt objective measures, and 10 studies used both. Pathological aging showed a worse impoverishment of sleep than older adults, in both subjective and objective measurements. The most common aspect compromised in AD and MCI were REM sleep, sleep efficiency, sleep latency, and sleep duration. These results underline that sleep alterations are associated with cognitive impairment. In conclusion, the frequency and severity of sleep disturbance appear to follow the evolution of cognitive impairment. The overall results of objective measures seem more consistent than those highlighted by subjective measurements.
Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Cognitive Dysfunction; Humans; Middle Aged; Sleep Quality; Sleep Wake Disorders
PubMed: 35886309
DOI: 10.3390/ijerph19148457 -
Ageing Research Reviews Jul 2021To investigate the effects of monoclonal antibodies against Aβ on cognition, function, amyloid PET and other biomarkers, as well as risk for amyloid-related imaging... (Meta-Analysis)
Meta-Analysis Review
Effects of monoclonal antibodies against amyloid-β on clinical and biomarker outcomes and adverse event risks: A systematic review and meta-analysis of phase III RCTs in Alzheimer's disease.
OBJECTIVE
To investigate the effects of monoclonal antibodies against Aβ on cognition, function, amyloid PET and other biomarkers, as well as risk for amyloid-related imaging abnormalities (ARIA) and other adverse events, in Alzheimer's disease (AD).
METHODS
Pubmed, Web of Science, ClinicalTrials.gov and gray literature were searched for phase III RCTs and random-effects meta-analyses were performed.
RESULTS
Seventeen studies (12,585 patients) were included. Antibodies statistically improved the cognitive outcomes ADAS-Cog {SMD = -0.06 [95 % CI (-0.10; -0.02), I = 0%]} and MMSE {SMD = 0.05 [95 % CI (0.01; 0.09), I = 0%]} by small effect sizes, but did not improve the cognitive/functional measure CDR-SOB {SMD = -0.03 [95 % CI (-0.07; 0.01), I = 18 %]}. Moreover, antibodies decreased amyloid PET SUVR {SMD = -1.02 [95 % CI (-1.70; -0.34), I = 95 %]} and CSF p181-tau {SMD = -0.87 [95 % CI (-1.32; -0.43), I = 89 %]} by large effect sizes. They also increased risk for ARIA {RR = 4.30 [95 % CI (2.39; 7.77), I = 86 %]} by a large effect size. Antibody effects on reducing amyloid PET SUVR were correlated with their effects on improving ADAS-Cog (r = +0.68, p = 0.02). In subgroup analyses by individual drug, Aducanumab improved ADAS-Cog, CDR-SOB, ADCS-ADL by small effect sizes and decreased amyloid PET SUVR and CSF p181-tau by large effect sizes. Solanezumab improved ADAS-Cog and MMSE by small effect sizes, and increased (improved) CSF Aβ levels by a moderate effect size. Bapineuzumab, Gantenerumab and Crenezumab did not improve any clinical outcomes. Bapineuzumab and Gantenerumab decreased CSF p181-tau by a small and large effect size, respectively. All drugs except Solanezumab increased ARIA risk.
CONCLUSIONS
In this meta-analysis of phase III trials in AD, we found that monoclonal antibodies against Aβ induced clinical improvements of small effect sizes, biomarker improvements of large effect sizes, and increases in risk for the hallmark adverse event, ARIA, by a large effect size, when all drugs were pooled together. Among individual drugs, Aducanumab produced the most favorable effects followed by Solanezumab. These findings provide moderate support for the continuous development of anti-Aβ monoclonal antibodies as a treatment for AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloidogenic Proteins; Antibodies, Monoclonal; Biomarkers; Clinical Trials, Phase III as Topic; Cognition; Humans; Randomized Controlled Trials as Topic
PubMed: 33831607
DOI: 10.1016/j.arr.2021.101339 -
International Journal of Environmental... Nov 2022A growing body of research has examined the effect of aerobic exercise on cognitive function in people with Alzheimer's Disease (AD), but the findings of the available... (Meta-Analysis)
Meta-Analysis Review
A growing body of research has examined the effect of aerobic exercise on cognitive function in people with Alzheimer's Disease (AD), but the findings of the available studies were conflicting. The aim of this study was to explore the effect of aerobic exercise on cognitive function in AD patients. Searches were performed in PubMed, Web of Science, and EBSCO databases from the inception of indexing until 12 November 2021. Cochrane risk assessment tool was used to evaluate the methodological quality of the included literature. From 1942 search records initially identified, 15 randomized controlled trials (RCTs) were considered eligible for systematic review and meta-analysis. Included studies involved 503 participants in 16 exercise groups (mean age: 69.2-84 years) and 406 participants (mean age: 68.9-84 years) in 15 control groups. There was a significant effect of aerobic exercise on increasing mini-mental state examination (MMSE) score in AD patients [weighted mean difference (WMD), 1.50 (95% CI, 0.55 to 2.45), = 0.002]. Subgroup analyses showed that interventions conducted 30 min per session [WMD, 2.52 (95% CI, 0.84 to 4.20), = 0.003], less than 150 min per week [WMD, 2.10 (95% CI, 0.84 to 3.37), = 0.001], and up to three times per week [WMD, 1.68 (95% CI, 0.46 to 2.89), = 0.007] increased MMSE score significantly. In addition, a worse basal cognitive status was associated with greater improvement in MMSE score. Our analysis indicated that aerobic exercise, especially conducted 30 min per session, less than 150 min per week, and up to three times per week, contributed to improving cognitive function in AD patients. Additionally, a worse basal cognitive status contributed to more significant improvements in cognitive function.
Topics: Humans; Aged; Aged, 80 and over; Alzheimer Disease; Randomized Controlled Trials as Topic; Cognition; Exercise
PubMed: 36497772
DOI: 10.3390/ijerph192315700