The Journal of Prevention of Alzheimer's Disease最新文献

Background

Easily accessible and self-administered cognitive assessments that can aid early detection for Alzheimer’s disease (AD) dementia risk are critical for timely intervention.

Objectives/Design

This cross-sectional study investigated continuous associations between Mayo Test Drive (MTD)–a remote, self-administered, multi-device compatible, web-based cognitive assessment–and AD-related imaging biomarkers.

Participants/Setting

684 adults from the Mayo Clinic Study of Aging and Mayo Clinic Alzheimer’s Disease Research Center participated (age=70.4±11.2, 49.7% female). Participants were predominantly cognitively unimpaired (CU; 94.0%).

Measurements

Participants completed (1) brain amyloid and tau PET scans and MRI scans for hippocampal volume (HV) and white matter hyperintensities (WMH); (2) MTD remotely, consisting of the Stricker Learning Span and Symbols Test which combine into an MTD composite; and (3) in-person neuropsychological assessment including measures to obtain Mayo Preclinical Alzheimer’s disease Cognitive Composite (Mayo-PACC) and Global-z. Multiple regressions adjusted for age, sex, and education queried associations between imaging biomarkers and scores from remote and in-person cognitive measures.

Results

Lower performances on MTD were associated with greater amyloid, entorhinal tau, and global tau PET burden, lower HV, and higher WMH. Mayo-PACC and Global-z were associated with all imaging biomarkers except global tau PET burden. MCI/Dementia participants showed lower performance on all MTD measures compared to CU with large effect sizes (Hedge’s g’s=1.65–2.02), with similar findings for CU versus MCI only (Hedge’s g’s=1.46–1.83).

Conclusion

MTD is associated with continuous measures of AD-related imaging biomarkers, demonstrating ability to detect subtle cognitive change using a brief, remote assessment in predominantly CU individuals and criterion validity for MTD.

Cognitive resilience has emerged as a mechanism that may help explain individual differences in cognitive function associated with aging and/or pathology. It is unknown whether an association exists between family income level and cognitive resilience. We performed a cross-sectional study to estimate the relationship between family income level and high cognitive resilience using the National Health and Nutrition Examination Survey (NHANES) among older adults (age≥60). Logistic regression was used to estimate the association between income level and high cognitive resilience adjusted for other factors. Accounting for differences in education, occupation, and health status, older adults in the highest income category were twice as likely compared to those with very low income to have high cognitive resilience (OR: 1.90, 95% CI: 1.05,3.43). A doseresponse was apparent between income category and high cognitive resilience. The finding that income, above and beyond that of known factors, affects cognitive function is important for future public health strategies that aim to prevent or delay cognitive impairment.

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by intricate genetic and environmental etiology. The objective of this study was to identify robust non-genetic risk factors for AD through an updated umbrella review.

Methods

We conducted a comprehensive search of meta-analyses and systematic reviews on non-genetic risk factors associated with AD in PubMed, Cochrane, Embase, and Ovid Medline up to June 30, 2023. After collecting data, we estimated the summary effect size and their 95% confidence intervals. The degree of heterogeneity between studies was assessed using I² statistics and a 95% prediction interval was determined. Additionally, we evaluated potential excess significant bias and small study effects within the selected candidate studies.

Results

The umbrella review encompassed a total of 53 eligible papers, which included 84 meta-analyses covering various factors such as lifestyle, diet, environmental exposures, comorbidity or infections, drugs, and biomarkers. Based on the evidence classification criteria employed in this study, two factors as convincing evidence (Class I), including rheumatoid arthritis (RA), potentially reduced the risk of AD, but diabetes significantly increased the risk of AD. Furthermore, three factors as highly suggestive evidence (Class II), namely depression, high homocysteine, and low folic acid level, potentially increased the risk of AD.

Conclusion

Our findings highlight several risk factors associated with AD that warrant consideration as potential targets for intervention. However, it is crucial to prioritize the identified modifiable risk factors, namely rheumatoid arthritis, diabetes, depression, elevated homocysteine levels, and low folic acid levels to effectively address this complex neurodegenerative disorder.

Background

Metabolic syndrome is associated with increased risk of dementia. Yet, findings on how longitudinal development of metabolic syndrome status affects cognition remain controversial.

Objectives

This study examines whether individuals with different changes in metabolic syndrome status differ in cognitive functioning. Additionally, the prevalence of metabolic syndrome within the Lifelines population-based study is investigated.

Design

14609 Lifelines participants (mean age 60.8, 56.4% women) were divided into four groups based on their metabolic syndrome status changes between 2007–2013 (1) and between 2014–2017 (2): without metabolic syndrome (N=10863; absent at 1 and 2), de novo metabolic syndrome (N=1340; absent at 1 and present at 2), remitting metabolic syndrome (N=825; present at 1 and absent at 2), and persistent metabolic syndrome (N=1581; present at 1 and 2). ANCOVA models were employed to assess group differences in psychomotor function, visual attention, visual learning, and working memory assessed using the Cogstate Brief Battery.

Results

Accounting for education, age, sex, and time between examinations, groups did not statistically differ in any of the four cognitive outcomes. The prevalence of metabolic syndrome within the Lifelines population increased with age and differed among men and women.

Conclusion

Performance in psychomotor function, visual attention, visual learning, and working memory measured by the Cogstate Brief Battery did not differ between individuals with different changes in metabolic syndrome. The length of metabolic syndrome exposure was unknown, making our results exploratory and calling for future studies addressing this gap.

Objective

Cognitive decline and dementia have been linked to cerebral small vessel disease, so we explored using Mendelian randomization whether cerebral small vessel disease visible as 10 neuroimaging signs may cause cognitive decline and dementia.

Methods

We analyzed publicly available data from genome-wide association studies using two-sample Mendelian randomization involving inverse variance weighting, weighted median, MR-Egger, and MR-PRESSO approaches.

Results

Mendelian randomization suggested that cognitive decline can be caused by lacunar stroke (inverse variance weighting, β = −0.012, 95% CI −0.024 to −0.001, P = 0.033). Furthermore, an elevated burden of white matter hyperintensities was associated with an increased risk of Dementia due to Parkinson’s disease (inverse variance weighting, OR 2.035, 95% CI 1.105 to 3.745, P = 0.023). Notably, no significant associations were observed between neuroimaging markers of Cerebral Small Vessel Disease and other types of dementia.

Conclusion

This Mendelian randomization study provides evidence that lacunar stroke and white matter lesions can cause cognitive decline, and that white matter hyperintensity may increase risk of dementia due to Parkinson’s disease. These results underscore the need for further investigations into the neurocognitive effects of cerebral small vessel disease.

Background

Since the beginning of Alzheimer’s disease research, the hypothesis that infections are to some extent associated with neurodegenerative processes has been tested repeatedly. Epidemiological studies on the associations between infections and dementia have reported conflicting results.

Objectives

This study analyses common hospital-treated infections (herpes, influenza, intestinal infections, pneumonia, sepsis, urinary tract infections) and their association with subsequent dementia and time until dementia onset.

Design, Setting, and Participants

For this nationwide population-based case-control study, the dataset of the Austrian National Health Insurance Association was used, including dementia patients (dementia cohort) and age- and gender-matched non-demented individuals (control cohort). Only subjects with data availability of at least 10 years prior to the index date (date of dementia diagnosis or date of censoring) were included.

Measurements

The incidence of six common infections in older adults (herpes, influenza, intestinal infections, pneumonia, sepsis, and urinary tract infections) was analyzed over a period of 10 years before the censoring date.

Results

The study population consists of 58208 subjects (29104 per study cohort), mean age: 81 years, 54% females. Patients of the dementia cohort had suffered from infections significantly more often than patients of the control cohort (6002, 20.6% vs. 4826, 16.6%; p < 0.001). Influenza, urinary tract infections, intestinal infections, and sepsis showed independent positive associations with subsequent dementia diagnosis, irrespective of other comorbidities (odds ratios: 1.26 (95% CI: 1.06–1.49), 1.23 (95% CI: 1.16–1.30), 1.16 (95% CI: 1.07–1.27), 1.17 (95% CI: 1.01–1.37), respectively). Time from infection to dementia diagnosis was shorter after influenza compared to all other infections (median: 3.4 years (95% CI: 3.1–3.7) vs. 6.6 years (95% CI: 6.4–6.8); p < 0.001).

Conclusion

This is the first study to assess the association between infections and dementia over such a long minimum reporting period. These results, supported by consistent data from other epidemiological studies, emphasize the critical importance of infection prevention measures, especially for older adults. Further research is crucial to better understand the nature of the relationship between infections and dementia.

Background and Objectives

To identify cognitive decline trajectories in a Chinese elderly population, explore the associations between these trajectories and mortality, and further identify risk factors related to certain trajectories of cognitive decline.

Design

Prospective cohort study.

Setting

The group-based trajectory modeling and Cox proportional hazards models were conducted to explore the association between cognitive trajectory groups and mortality, while multinomial logistic regression models were constructed to estimate potential risk factors.

Participants

We included 7082 participants aged 65 years or above in three consecutive but non-overlapping cohorts of the Chinese Longitudinal Healthy Longevity Survey with the Chinese version of the Mini-Mental State Examination up to 6 years. Participants were subsequently followed for a median (IQR) of 2.89 (1.38–3.12) years to obtain their survival status and date of death.

Measurements

Chinese version of the Mini-Mental State Examination was used to measure participants’ cognitive function.

Results

Through use of group-based trajectory modeling, we determined three cognitive trajectory groups. Then, after adjusting for confounding factors, we found a monotonic and positive association between cognitive decline and mortality risk. Meanwhile, the association varied among elderly populations in different age groups and BMI categories, but did not differ by sex, smoking, drinking and exercising. Older seniors, females and those with poorer baseline cognitive function and less social participation tended to be more likely to be in the unfavorable trajectory groups.

Conclusion

We found that the faster the cognitive decline, the higher the mortality, especially among those aged 65–79 years and those overweight. Our findings suggested the importance of implement better monitoring of the cognitive function of the elderly population.

Background

The BCG vaccine has been traditionally administered to prevent TB. It has been additionally used in bladder cancer patients as a therapy with success. Some observational studies found that bladder cancer patients receiving BCG may have reduced dementia risk, however, the evidence is not conclusive.

Objective

To investigate the impact of BCG vaccine on dementia risk in bladder cancer patients.

Methods

Six databases were searched from inception to January 13, 2024, for published and unpublished studies that examine the association between BCG and dementia risk in bladder cancer patients. We conducted meta-analyses using a random-effects model.

Results

Eight retrospective cohort studies were included in the systematic review and seven in the meta-analyses. Because there were studies with overlapping populations, two separate main analyses were performed reassuring the avoidance of overlap. The first analysis showed that compared to controls, BCG did not reduce dementia risk [5 studies pooled, n=88,852, HR = 0.65, 95% CI (0.40, 1.06), I² = 85%] whereas there was a marginally significant risk reduction in the second analysis [6 studies pooled, n=70,025, HR = 0.63, 95% CI (0.40, 0.97), I² = 83%]. Sensitivity analysis excluding the unpublished studies did not affect the outcome importantly. Additional meta-analysis showed that BCG did not reduce the risk of Alzheimer’s disease.

Conclusion

This meta-analysis of observational studies found that BCG administration in bladder cancer patients has likely a minimally positive impact on dementia risk if any. To better understand the effect of BCG on dementia, randomized controlled trials are needed.

Affordable, rapid methods for identifying mild Alzheimer’s disease (AD) are needed. A simple, brief performance-based test involving the learning of functional upper-extremity movements has been developed and is associated with AD pathology and functional decline. However, its specificity to AD relative to other neurodegenerative diseases that present with motor impairment is unknown. This study examined whether this novel test could distinguish between 34 participants diagnosed with mild AD (Clinical Dementia Rating Scale = 0.5–1) from 23 participants with mild-to-moderate Parkinson’s disease (PD) (Hoehn & Yahr = 2–3) using Receiver Operating Characteristic analysis of secondary data from two separate clinical trials. Indicators of diagnostic accuracy demonstrated that the test identified participants with AD, who had worse scores than those with PD, suggesting it may be a viable screening tool for mild AD. Exploratory analyses with a control group (n=52) further showed that test scores were not sensitive to motor dysfunction.