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Alzheimer's & Dementia : the Journal of... Nov 2022Hypertension is an important risk factor for Alzheimer's disease (AD) and all-cause dementia. The mechanisms underlying this association are unclear. Hypertension may be... (Review)
Review
Hypertension is an important risk factor for Alzheimer's disease (AD) and all-cause dementia. The mechanisms underlying this association are unclear. Hypertension may be associated with AD neuropathological changes (ADNC), but reports are sparse and inconsistent. This systematic review included 15 autopsy studies (n = 5879) from observational cohorts. Studies were highly heterogeneous regarding populations, follow-up duration, hypertension operationalization, neuropathological methods, and statistical analyses. Hypertension seems associated with higher plaque and tangle burden, but results are inconsistent. Four studies (n = 3993/5879; 68%), reported clear associations between hypertension and ADNC. Another four suggested that antihypertensive medication may protect against ADNC. Larger studies with longer follow-up reported the strongest relationships. Our findings suggest a positive association between hypertension and ADNC, but effects may be modest, and possibly attenuate with higher hypertension age and antihypertensive medication use. Investigating interactions among plaques, tangles, cerebrovascular pathology, and dementia may be key in better understanding hypertension's role in dementia development.
Topics: Humans; Alzheimer Disease; Neurofibrillary Tangles; Autopsy; Antihypertensive Agents; Plaque, Amyloid; Hypertension; Brain
PubMed: 35758526
DOI: 10.1002/alz.12707 -
Medicina (Kaunas, Lithuania) Dec 2022: People with Alzheimer's disease and dementia in general benefit from home-based care as demonstrated via their better quality of life, increased lifespan, and delayed... (Review)
Review
: People with Alzheimer's disease and dementia in general benefit from home-based care as demonstrated via their better quality of life, increased lifespan, and delayed disease progression. Since currently nearly half of the dementia care is being provided by informal and unpaid caregiving, the health, wellbeing and quality of life of informal dementia caregivers is extremely important. : We used a systematic review process with searches based upon the six elements from the "Quality of Life Scale for Informal Carers of Older Adults" with additional items on traditional and non-traditional caregiving ideologies, as well as caregivers' experiences. : We identified 19 studies with primary data. Informal caregivers of older adults with Alzheimer's Disease experience significant emotional strain, documented through increased levels of anxiety and depression, as well as increased caregiver burden and poorer quality of life, primarily due to caregiving ideologies, financial strain and a lack of support. : Our findings suggest that caregiving should be a normative component of adult education to better prepare individuals with the mental and physical skills required for undertaking informal caregiving. They should also help inform policy makers to develop novel programs and services to both assist and reduce informal caregivers' strain, whilst considering their different social and cultural contexts.
Topics: Humans; Aged; Alzheimer Disease; Quality of Life; Caregivers; Home Care Services
PubMed: 36676672
DOI: 10.3390/medicina59010048 -
International Journal of Stroke :... Jan 2023The interrelationships between gait, cerebral small vessel disease (CSVD), and cognitive impairments in aging are not well-understood-despite their common co-occurrence. (Review)
Review
BACKGROUND
The interrelationships between gait, cerebral small vessel disease (CSVD), and cognitive impairments in aging are not well-understood-despite their common co-occurrence.
OBJECTIVE
To systematically review studies of gait impairment in CSVD, pre-dementia, and dementia, and to identify key gaps for future research and novel pathways toward intervention.
METHODS
A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided search strategy was implemented in PubMed to identify relevant studies. Potential articles (n = 263) published prior to 1 December 2021 were screened by two reviewers. Studies with sample sizes >20 and including some adults over > 65 years (n = 202) were included.
RESULTS
The key findings were that (1) adverse gait and cognitive outcomes were associated with several (rather than select) CSVD pathologies distributed across the brain, and (2) poor gait and CSVD pathologies were more strongly associated with dementia with a vascular, rather than an Alzheimer's disease-related, cause.
DISCUSSION
A better understanding of the interrelationships between gait performance in CSVD, pre-dementia, and dementia requires studies examining (1) comprehensive patterns in the clinical manifestations of CSVD, (2) racially/ethnically diverse samples, (3) samples followed for extended periods of time or across the adult life span, (4) non-traditional CSVD neuroimaging markers (e.g. resting-state functional magnetic resonance imaging (fMRI)), and (5) continuous (e.g. wearable sensors) and complex (e.g. dual-task) walking performance.
Topics: Adult; Humans; Stroke; Brain; Cerebral Small Vessel Diseases; Alzheimer Disease; Gait; Magnetic Resonance Imaging
PubMed: 35797006
DOI: 10.1177/17474930221114562 -
Aging Clinical and Experimental Research Mar 2024Dementia affects 5-8% of the population aged over 65 years (~50 million worldwide). Several factors are associated with increased risk, including diet. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dementia affects 5-8% of the population aged over 65 years (~50 million worldwide). Several factors are associated with increased risk, including diet. The Mediterranean diet (MedDiet) has shown potential protective effects against several chronic diseases.
AIMS
This systematic review with meta-analysis aim was to assess the association between adherence to the MedDiet and the risk of dementia in the elderly.
METHODS
PRISMA-2020 guidelines were followed. PubMed/MEDLINE and Scopus were searched on 17 July 2023. The Newcastle-Ottawa Scale tool was used to assess the risk of bias. The protocol was pre-registered in PROSPERO (registration number: CRD 42023444368). Heterogeneity was assessed using the I test. Publication bias was assessed by visual inspection of the funnel plot and by Egger's regression asymmetry test. The final effect size was reported as OR or HR, depending on the study design of the included studies.
RESULTS
Out of 682 records, 21 were included in the analysis. The pooled OR was 0.89 (95% CI = 0.84-0.94) based on 65,955 participants (I = 69.94). When only cohort studies were included, HR was 0.84 (95% CI = 0.76-0.94) based on 55,205 participants (I = 89.70). When only Alzheimer Disease was considered OR was 0.73 (95% CI = 0.62-0.85) based on 38,292 participants (I = 63.85).
DISCUSSION
Despite the relatively low risk reduction associated with higher adherence to MedDiet among elderly, it should be considered that this population is the most affected.
CONCLUSIONS
Adherence to MedDiet could be an effective non-pharmacological measure to reduce the burden of dementia, even among elderly.
Topics: Aged; Humans; Alzheimer Disease; Diet, Mediterranean; Cohort Studies; Risk; Research Design
PubMed: 38519775
DOI: 10.1007/s40520-024-02718-6 -
Clinical and Experimental Nephrology Jan 2022To identify the association between albuminuria and dementia or cognitive impairment. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To identify the association between albuminuria and dementia or cognitive impairment.
METHODS
The literature search was performed to identify relevant scientific studies through August 2019, including PubMed/Medline and EMBASE. For inclusion, the studies had to fulfil the following criteria: population-based cohort, case-control or cross-sectional studies; quantifying an association of albuminuria with cognitive impairment or dementia; and reported odds ratio (OR), and the corresponding 95% confidential interval (95% CI). Random effects model was used to yield pooled estimates.
RESULTS
A total of 16 studies (11 cohort studies and five cross-sectional studies) were included in the meta-analyses. Based on the fully adjusted estimates, albuminuria was associated with a significant higher risk of cognitive impairment or dementia. Furthermore, the same trend existed for cognitive impairment and dementia, respectively. In addition, both of Alzheimer's diseases (AD) and vascular dementia (VaD) were significantly associated with albuminuria.
CONCLUSION
Albuminuria was significantly associated with cognitive impairment and dementia. Corresponding to an earlier subclinical time-point in kidney disease progress, albuminuria may be a potential factor predicting the future occurrence of dementia.
Topics: Albuminuria; Alzheimer Disease; Cognitive Dysfunction; Cross-Sectional Studies; Dementia; Humans
PubMed: 34468878
DOI: 10.1007/s10157-021-02127-3 -
Molecular Neurodegeneration Nov 2022The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely... (Review)
Review
The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely resolved, they have been recognized for their signaling engagements and trafficking abilities, navigating a number of molecules between endosome, Golgi compartments, and the cell surface. Strikingly, recent studies connected all the VPS10p-D receptors to Alzheimer's disease (AD) development. In addition, they have been also associated with diseases comorbid with AD such as diabetes mellitus and major depressive disorder. This systematic review elaborates on genetic, functional, and mechanistic insights into how dysfunction in VPS10p-D receptors may contribute to AD etiology, AD onset diversity, and AD comorbidities. Starting with their functions in controlling cellular trafficking of amyloid precursor protein and the metabolism of the amyloid beta peptide, we present and exemplify how these receptors, despite being structurally similar, regulate various and distinct cellular events involved in AD. This includes a plethora of signaling crosstalks that impact on neuronal survival, neuronal wiring, neuronal polarity, and synaptic plasticity. Signaling activities of the VPS10p-D receptors are especially linked, but not limited to, the regulation of neuronal fitness and apoptosis via their physical interaction with pro- and mature neurotrophins and their receptors. By compiling the functional versatility of VPS10p-D receptors and their interactions with AD-related pathways, we aim to further propel the AD research towards VPS10p-D receptor family, knowledge that may lead to new diagnostic markers and therapeutic strategies for AD patients.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Depressive Disorder, Major; Protein Transport; Nerve Growth Factors
PubMed: 36397124
DOI: 10.1186/s13024-022-00576-2 -
Medicine Oct 2023Herpes Zoster, commonly known as shingles, is a viral infection that affects a significant portion of the adult population; however, its potential role in the onset or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Herpes Zoster, commonly known as shingles, is a viral infection that affects a significant portion of the adult population; however, its potential role in the onset or progression of neurodegenerative disorders like dementia remains unclear.
METHODS
We searched the following databases: PubMed, Scopus, Cochrane library, and Web of Science. We included any randomized control trials and controlled observational studies as Cross-sectional, prospective, or retrospective cohort and case-control studies that investigated the prevalence of dementia in Herpes Zoster Virus (HZV)-infected patients and HZV-free control group or if the study investigated the prevalence of HZV in demented patients. Also, if the studies measured the levels of dementia biomarkers in patients with HZV compared with a healthy control group.
RESULTS
After the complete screening, 9 studies were included in the meta-analysis. In the outcome of the incidence of HZV, the pooled analysis showed no statistically significant difference between the dementia group and the No dementia group (RR = 1.04% CI = 0.86-1.25, P = .70). In the outcome of incidences of dementia and Alzheimer's disease, the pooled analysis showed no statistically significant difference between the HZV group and the incidence of dementia (RR = 0.99, 95% CI = 0.92-1.08, P = .89), (RR = 3.74, 95% CI = 0.22-62.70, P = .36) respectively. In the outcome of incidences of Herpes Zoster ophthalmicus (HZO), the generic inverse variance showed a statistically significant association between patients who have HZO and increased incidence of dementia (RR = 6.26, 95% CI = 1.30-30.19, P = .02).
CONCLUSION
Our study showed no significant association between HZV and the incidence of dementia or Alzheimer's disease, but it shows a significant association between HZO and the incidence of dementia. More multicenter studies are needed to establish the actual association between the HZV and dementia.
Topics: Adult; Humans; Herpesvirus 3, Human; Retrospective Studies; Alzheimer Disease; Prospective Studies; Cross-Sectional Studies; Herpes Zoster; Chickenpox
PubMed: 37904465
DOI: 10.1097/MD.0000000000034503 -
The Cochrane Database of Systematic... Dec 2020Souvenaid is a dietary supplement with a patented composition (Fortasyn Connect™)which is intended to be used by people with Alzheimer's disease (AD). It has been...
BACKGROUND
Souvenaid is a dietary supplement with a patented composition (Fortasyn Connect™)which is intended to be used by people with Alzheimer's disease (AD). It has been designed to support the formation and function of synapses in the brain, which are thought to be strongly correlated with cognitive function. If effective, it might improve symptoms of Alzheimer's disease and also prevent the progression from prodromal Alzheimer's disease to dementia. We sought in this review to examine the evidence for this proposition.
OBJECTIVES
To assess the effects of Souvenaid on incidence of dementia, cognition, functional performance, and safety in people with Alzheimer's disease.
SEARCH METHODS
We searched ALOIS, i.e. the specialised register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), Web of Science (ISI Web of Science), Cinahl (EBSCOhost), Lilacs (BIREME), and clinical trials registries up to 24 June 2020. We also reviewed citations of reference lists of landmark papers, reviews, and included studies for additional studies and assessed their suitability for inclusion in the review.
SELECTION CRITERIA
We included randomised, placebo-controlled trials which evaluated Souvenaid in people diagnosed with mild cognitive impairment (MCI) due to AD (also termed prodromal AD) or with dementia due to AD, and with a treatment duration of at least 16 weeks.
DATA COLLECTION AND ANALYSIS
Our primary outcome measures were incidence of dementia, global and specific cognitive function, functional performance, combined cognitive-functional outcomes and adverse events. We selected studies, extracted data, assessed the quality of trials and intended to conduct meta-analyses according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. We present all outcomes grouped by stage of AD.
MAIN RESULTS
We included three randomised, placebo-controlled trials investigating Souvenaid in 1097 community-dwelling participants with Alzheimer's disease. One study each included participants with prodromal AD, mild AD dementia and mild-to-moderate AD dementia. We rated the risks of bias of all trials as low. One study (in prodromal AD) was funded by European grants. The other two studies were funded by the manufacturer of Souvenaid. One trial investigated the incidence of dementia in people with prodromal AD at baseline, and found little to no difference between the Souvenaid group and the placebo group after 24 months (RR 1.09, 95% CI 0.82 to 1.43; 1 trial, 311 participants; moderate quality of evidence). In prodromal AD, and in mild and mild-to-moderate Alzheimer's disease dementia, Souvenaid probably results in little or no difference in global or specific cognitive functions (moderate quality of evidence). Everyday function, or the ability to perform activities of daily living, were measured in mild and mild-to-moderate AD dementia. Neither study found evidence of a difference between the groups after 24 weeks of treatment (moderate quality of evidence). Two studies investigated combined cognitive-functional outcomes with the Clinical Dementia Rating Sum of Boxes and observed conflicting results. Souvenaid probably results in slight improvement, which is below estimates of meaningful change, in participants with prodromal Alzheimer's disease after 24 months (moderate quality of evidence), but probably has little to no effect in mild-to-moderate Alzheimer's disease dementia after 24 weeks (moderate quality of evidence). Adverse effects observed were low in all trials, and the available data were insufficient to determine any connection with Souvenaid.
AUTHORS' CONCLUSIONS
Two years of treatment with Souvenaid probably does not reduce the risk of progression to dementia in people with prodromal AD. There is no convincing evidence that Souvenaid affects other outcomes important to people with AD in the prodromal stage or mild-to-moderate stages of dementia. Conflicting evidence on combined cognitive-functional outcomes in prodromal AD and mild AD dementia warrants further investigation. Adverse effects of Souvenaid seem to be uncommon, but the evidence synthesised in this review does not permit us to make a definitive statement on the long-term tolerability of Souvenaid. The effects of Souvenaid in more severe AD dementia or in people with AD at risk of nutritional deficiencies remain unclear.
Topics: Alzheimer Disease; Bias; Cognition; Dementia; Dietary Supplements; Disease Progression; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Phospholipids; Placebos; Prodromal Symptoms; Randomized Controlled Trials as Topic; Time Factors
PubMed: 33320335
DOI: 10.1002/14651858.CD011679.pub2 -
BMC Medicine Jan 2021The etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on...
BACKGROUND
The etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on single contributing factors or diseases, no study has systematically captured non-purely genetic risk and/or protective factors for chronic neurological diseases.
METHODS
We performed a systematic analysis of umbrella reviews (meta-umbrella) published until September 20th, 2018, using broad search terms in MEDLINE, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations & Theses, JBI Database of Systematic Reviews and Implementation Reports, DARE, and PROSPERO. The PRISMA guidelines were followed for this study. Reference lists of the identified umbrella reviews were also screened, and the methodological details were assessed using the AMSTAR tool. For each non-purely genetic factor association, random effects summary effect size, 95% confidence and prediction intervals, and significance and heterogeneity levels facilitated the assessment of the credibility of the epidemiological evidence identified.
RESULTS
We identified 2797 potentially relevant reviews, and 14 umbrella reviews (203 unique meta-analyses) were eligible. The median number of primary studies per meta-analysis was 7 (interquartile range (IQR) 7) and that of participants was 8873 (IQR 36,394). The search yielded 115 distinctly named non-genetic risk and protective factors with a significant association, with various strengths of evidence. Mediterranean diet was associated with lower risk of dementia, Alzheimer disease (AD), cognitive impairment, stroke, and neurodegenerative diseases in general. In Parkinson disease (PD) and AD/dementia, coffee consumption, and physical activity were protective factors. Low serum uric acid levels were associated with increased risk of PD. Smoking was associated with elevated risk of multiple sclerosis and dementia but lower risk of PD, while hypertension was associated with lower risk of PD but higher risk of dementia. Chronic occupational exposure to lead was associated with higher risk of amyotrophic lateral sclerosis. Late-life depression was associated with higher risk of AD and any form of dementia.
CONCLUSIONS
We identified several non-genetic risk and protective factors for various neurological diseases relevant to preventive clinical neurology, health policy, and lifestyle counseling. Our findings could offer new perspectives in secondary research (meta-research).
Topics: Biomarkers; Diet, Mediterranean; Exercise; Humans; Hypertension; Nervous System Diseases; Protective Factors; Risk Factors
PubMed: 33435977
DOI: 10.1186/s12916-020-01873-7 -
PloS One 2023Atopic dermatitis (AD) is a common chronic inflammatory skin disease that affects adults worldwide. Recent evidence suggests that AD may be associated with cognitive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atopic dermatitis (AD) is a common chronic inflammatory skin disease that affects adults worldwide. Recent evidence suggests that AD may be associated with cognitive dysfunction, but the results of individual studies have been inconsistent. This systematic review and meta-analysis aimed to evaluate the association between AD and cognitive dysfunction in middle-aged and older adults.
METHODS
To find relevant research, a comprehensive search of electronic databases from the beginning to March 2023 was carried out. Data were taken from studies that were eligible, and a meta-analysis was done to determine the pooled hazard ratio (HR) and 95% confidence interval (CI).
RESULTS
We searched three databases and found a total of 15 studied arms included in 5 cohort studies with over 8.5 million participants were included in the analysis. The results showed that individuals with AD had a higher risk of developing dementia of all-cause dementia (pooled hazard ratio (HR) = 1.16; 95% CI, 1.10-1.23,P<0.001) and the Alzheimer type (pooled HR = 1.28; 95% CI, 1.01-1.63,P<0.001) but not vascular dementia (pooled HR = 1.42; 95% CI, 0.99-2.04,P<0.001). Subgroup analyses showed that the association between atopic dermatitis and all-cause dementia was significant in Europe (P = 0.004) but not in Asia (P = 0.173) and was significant in prospective cohort studies (P<0.001) but not in non-prospective cohort studies (P = 0.068). Sensitivity analysis and publication bias detection confirmed the reliability of the overall findings.
CONCLUSIONS
In conclusion, this study demonstrated that AD was associated with increased risk of cognitive dysfunction, particularly dementia of the Alzheimer type and all-cause dementia, in middle-aged and older participants. Further research is needed to understand the mechanisms behind this association and its potential implications for clinical practice.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier (CRD42023411627).
Topics: Middle Aged; Humans; Aged; Alzheimer Disease; Dermatitis, Atopic; Prospective Studies; Reproducibility of Results; Cognitive Dysfunction
PubMed: 37878635
DOI: 10.1371/journal.pone.0292987