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

Background

Updated prevalence estimates along the continuum of Alzheimer’s disease (AD) can foster a more nuanced and effective approach to managing AD within the current healthcare landscape.

Objectives

This study aims to estimate the prevalence and severity distribution of dementia/AD (including mild, moderate, and severe stages) and all-cause mild cognitive impairment (MCI) in the United States using data from the Health and Retirement Study (HRS).

Design

Retrospective study.

Setting

Data from the bi-annual HRS surveys involving in-depth interviews of a representative sample of Americans aged >50 years.

Participants

Dementia/AD and all-cause MCI patients from the 4 most recent HRS surveys (2014, 2016, 2018 and 2020).

Measurements

AD was identified based on diagnosis (self-report). Cognitive performance (modified Telephone Interview of Cognitive Status [TICS-m]) scores in the dementia/AD range were also captured; all-cause MCI was similarly identified using the TICS-m. Dementia/AD and MCI prevalence, as well as the distribution by dementia/AD stage (mild, moderate, or severe), were estimated. Sampling weights developed by HRS were applied to ensure the sample’s representativeness of the target population and unbiased estimates for population parameters.

Results

Across the four HRS surveys, the total number of HRS respondents ranged from 15,000 to 21,000 (unweighted); 7,000 to 14,000 had TICS-m scores. The estimated prevalence of AD (all severity categories combined) in the 2014, 2016, 2018, and 2020 HRS surveys was 1.2%, 1.2%, 1.3% and 1.0%, respectively using the diagnosis-based approach; using the cognitive performance-based approach, 23–27% patients had scores in the dementia/AD ranges across the 4 surveys. The estimated prevalence of all-cause MCI was consistently 23% in each survey. In the 2020 survey, the distribution of mild, moderate, and severe disease stages was 34%, 45%, and 21%, respectively, in patients self-reporting an AD diagnosis, and 55%, 40%, and 5%, respectively in all patients meeting TICS-m threshold for dementia/AD.

Conclusion

The prevalence of AD diagnosis based on self-report was approximately 1% across the 4 most recent HRS surveys and may reflect the proportion of patients who have actively sought healthcare for AD. Among HRS survey respondents with cognitive scores available, over 20% were in the dementia/AD range. The distribution of disease by stage differed for self-reported AD diagnosis vs dementia/AD based on cognitive scores. Discordance in estimates of dementia/AD and stage distributions underscores a need for better understanding of clinica

Background

Little is known about the impact of short, low-intensity multidomain dementia risk reduction interventions in older adults.

Objectives

To examine the effectiveness and feasibility of a low-intensity multidomain lifestyle intervention on dementia risk and dementia literacy in Australian older adults.

Design

Single-group pre-post design.

Setting

Community-dwelling.

Participants

A total of 853 older Australians (Mean age=73.3 years, SD=6.1) recruited from the community.

Intervention

A 3-month dementia risk reduction program, BRAIN BOOTCAMP, including education, personalised risk information, physical cues for healthier choices and goal setting and planning to target four modifiable risk factors of diet, exercise, cognitive activity and social interaction in older adults.

Measurements

The ‘LIfestyle for BRAin health’ (LIBRA) index was used to assess participants’ modifiable dementia risk based on 12 factors, with higher scores indicating greater risk. Dementia literacy was measured using a modified questionnaire derived from Dutch and British surveys, encompassing knowledge, risk reduction, and awareness aspects. Paired t-tests were used to compare dementia risk scores and dementia literacy before and after the program. Multivariate regressions were performed to identify sociodemographic and psychological factors associated with change in the LIBRA index.

Results

Program attrition was high (58.3%). Participants who completed the program had decreased dementia risk scores (Cohen’s d=0.59, p<0.001), increased dementia literacy and awareness (Cohen’s d=0.64, p<0.001) and increased motivation to change lifestyle behaviors (Cohen’s d=0.25–0.52, p<0.016). Participants with higher motivational beliefs had greater dementia risk reduction.

Conclusions

Improving older adults’ motivation and knowledge may help modify lifestyle behaviors to reduce dementia risk. However, program attrition remains a challenge, suggesting the need for strategies to enhance participant engagement and retention in such interventions.

Background

The preceding evidence indicates a close correlation between imbalances in the gut microbiome and Alzheimer’s disease (AD), yet the direct causal relationship remains unclear. Our objective is to investigate this potential causal connection.

Methods

We obtained summary results from two significant genome-wide association studies (GWAS) on gut microbiota (the MibioGen consortium and the Dutch Microbiome Project), along with one GWAS summary result for AD. Using a two-sample Mendelian randomization (TSMR) analysis, we examined the potential causal effects of gut microbiota on AD.

Results

Our TSMR analysis revealed that 16 gut bacterial taxa were linked to a reduced risk of AD. These included phylum Tenericutes, classes Bacilli and Clostridia along with its order Clostridiales, family Bacteroidaceae, genus Bacteroides, and species Bifidobacterium bifidum (OR: 0.867∼0.971, P ≤ 0.045). Conversely, the presence of 12 taxa correlated with an increased risk of AD. These comprised class Actinobacteria and its family Coriobacteriaceae, as well as class Betaproteobacteria, its order Burkholderiales, and its family Sutterellaceae (OR: 1.042∼1.140, P ≤ 0.035).

Conclusion

Our research uncovered evidence suggesting certain gut bacterial species might play a causal role in AD risk, providing a fresh angle for AD treatment strategies.

Recent positive results of three phase III anti-amyloid monoclonal antibody trials are transforming the landscape of disease-modifying therapeutics for Alzheimer’s disease, following several decades of failures. Indeed, all three trials have met their primary endpoints. However, the absolute size of the benefit measured in these trials has generated a debate on whether the change scores observed on clinical outcome assessments represent a clinically meaningful benefit to patients. An evidence-based conclusion is urgently required to inform decision-making related to the approval, reimbursement, and ultimately, the management of emerging therapies in clinical practice. The EU-US CTAD Task Force met in Boston to address this important question. The current state-of-the-art knowledge for interpreting clinical meaningfulness of AD clinical trial results, including the point of view of patients and study partners on what is clinically meaningful, was discussed and is summarized here. A combination of methodologies to address the challenges emerged. There remain gaps in the understanding of clinical meaningfulness that only long-term longitudinal studies will be able to address.

Background

Reversal of cognitive frailty through a multidomain intervention is desirable to prevent dementia. AGELESS Trial was conducted to determine the effectiveness of a comprehensive, multidomain intervention on older adults with cognitive frailty in Malaysia. However, conducting a clinical trial, particularly during and after Covid-19, posed unique challenges.

Objective

We aimed to investigate the recruitment process and baseline characteristics of the AGELESS Trial participants to better understand an at-risk population and those who agree to participate in an intervention.

Design/Setting

24-month, randomized controlled trial.

Participants

Community-dwelling older adults with independent mobility, aged ≥ 60 years, with a mini mental state examination score of 19–25, a clinical dementia rating of 0.5 ≥ 1 Fried’s physical frailty criteria, and < 22 Beck depression inventory.

Intervention

Participants were randomized 1:1 to a structured multidomain intervention consisting of vascular management, diet, exercise, cognitive and psychosocial stimulation, or to the arm, including routine care and general health consultation.

Measurement

We analyzed the group differences between (1) cognitive frailty and non-cognitive frailty screened subjects, (2) recruited and non-recruited participants, (3) baseline characteristics of participants by arm, (4) adherence to AGELESS intervention at 12 months, and (5) preliminary findings on the effectiveness of the intervention at 12 months.

Results

A total of 957 older adults from two locations, i.e., urban (n = 764) and rural (n = 193) areas, were screened, of whom 38.9% had cognitive frailty and were eligible to participate. Those with cognitive frailty had fewer years of education (B = −0.08; 95%CI = 0.88–0.97; p = 0.002), and lower functioning cognition (B = −0.24; 95%CI = 0.74–0.84; p < 0.001). Among those from urban areas, only 33.1% (n = 106) agreed to participate, particularly those with multimorbidity (B = 0.86; 95%CI = 1.31–4.30; p = 0.01), higher physical activity (B = −1.02; 95%CI = 0.19–0.69; p = 0.002), slower walking speed (B = 1.26; 95%CI = 1.62–7.61; p = 0.001), and higher systolic blood pressure (B = 0.02; 95%CI = 1.00–1.03; p = 0.03). At baseline, participants’ mean age was 68.1±5.6, years of education was 8.3±3.9, body mass index was 27.5±5.3 kg/m², and mini mental state examination score was 22.7±4.0. Generally, there were no significant differences between the intervention and control groups for the main outcomes, except those in the intervention group had higher body mass index, mid-upper-arm circumference, and waist circumference (p < 0.05 for all par

Background

Alzheimer’s disease (AD), the main type of dementia, involves in complex pathophysiological processes, including abnormal lysosomes function. Cathepsins are the predominant proteases responsible for the degradation of diverse substrates in the endo-lysosomal system. However, there was still a lack of systematic study on the causal association between cathepsins and AD.

Methods

This study utilized Mendelian randomization (MR) to investigate the association between blood cathepsins and the risk of AD, as well as the level of amyloid-β (Aβ) and p-Tau in cerebrospinal fluid. Furthermore, an independent dataset was employed to corroborate the above result. Importantly, this study incorporated the Alzheimer’s disease Immunization and Microbiota Initiative study Cohort to further validate the alteration of blood cathepsins expression level and examine its correlation with cognitive level and plasma AD-related pathological markers.

Results

Using MR method, we observed that high level of cathepsin L (CTSL) was associated with a lower risk of AD in both training and validation data. In observational cohort, we found there was decreased blood CTSL expression level in Aβ+ cognitive impaired (CI) group, compared with Aβ− cognitive unimpaired (CU) group. Correlation analysis revealed that blood CTSL expression level was negatively correlated with Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) score, plasma Aβ42 and Aβ42/40 level in Aβ+ CI group. Mediation analysis showed that plasma Aβ42/40 level was the key mediator in the association between blood CTSL and MMSE score in Aβ+ CI participants.

Conclusion

This study revealed that blood CTSL was an important factor affecting the risk of AD, and it affected the cognitive level of AD patients through plasma Aβ42/40 level.

Background

Advances in plasma biomarkers to detect Alzheimer’s disease (AD) biology allows researchers to improve the efficiency of participant recruitment into preclinical trials. Recently, protein levels of plasma amyloid-beta and tau proteins have been shown to be predictive of elevated amyloid in brain. Online registries, such as the Alzheimer’s Prevention Trials (APT) Webstudy, include and follow participants using remote assessments to facilitate efficient screening and enrollment of large numbers of individuals who may be at higher risk for AD.

Objectives

The AlzMatch Pilot Study investigated the feasibility of recruiting individuals from an online registry for blood sample collection at community-based phlebotomy centers and plasma biomarker quantification to assess an individual’s eligibility for AD preclinical trials.

Design

Pilot feasibility study with co-primary outcomes.

Setting

This pilot feasibility study included participants from the APT Webstudy, the remote assessment arm of the Trial-ready cohort for Preclinical and Prodromal AD (TRC-PAD) Platform. Novel design included collection of electronic consent, use of community laboratories for plasma collection, mass spectrometry-based biomarker assay, and telephone communication of plasma biomarker screening eligibility.

Participants

Participants invited to the AlzMatch pilot feasibility study were active in the APT Webstudy, 50 years of age or older, resided within 50 miles of both a Quest Diagnostics Patient Services Center (a national diagnostic laboratory with convenient locations for sample collection and processing) and one of six TRC-PAD vanguard clinical trial sites, had no self-reported dementia diagnosis, were able to communicate in English and engaged with the APT Webstudy within the prior 6 months.

Measurements

Primary feasibility outcomes were completion of electronic consent (e-consent) for invited participants and collection of usable blood samples. Additional feasibility outcomes included invitation response rate, plasma biomarker eligibility status (based on amyloid beta-42/40 [Aβ42/40] concentration ratio), ApoE proteotype, and trial inclusion criterion), and completion of telephone contact to learn eligibility to screen for a study.

Results

300 APT Webstudy participants were invited to consent to the AlzMatch study. The AlzMatch e-consent rate was 39% (n=117) (95% CI of 33.5%–44.5%) overall, which was higher than the expected rate of 25%. Similar consent rates were observed across participants based on self-defined sex (41% Female (n=75), 37% Male (n=42)) and race and ethnicity (37% from underrepresented groups (URG) (n=36), 40% not from URG (n=

Background

It has been suggested that up to 40% of dementia cases worldwide are associated with modifiable risk factors; however, these estimates are not known in Canada. Furthermore, sleep disturbances, an emerging factor, has not been incorporated into the life-course model of dementia prevention.

Objective

To estimate the population impact of 12 modifiable risk factors in Canadian adults including sleep disturbances, by sex and age groups, and to compare with other countries.

Design

Cross-sectional analysis of Canadian Longitudinal Study on Aging baseline data.

Setting

Community.

Participants

30,097 adults aged 45 years and older.

Measuremments

Prevalence and Population Attributable

Fractions (PAFs) associated with less education, hearing loss, traumatic brain injury, hypertension, excessive alcohol, obesity, smoking, depression, social isolation, physical inactivity, diabetes, and sleep disturbances

Results

The risk factors with the largest PAF were later life physical inactivity (10.2%; 95% CI, 6.8% to 13%), midlife hearing loss (6.5%; 3.7% to 9.3%), midlife obesity (6.4%; 4.1% to 7.7%), and midlife hypertension (6.2%; 2.7% to 9.3%). The PAF of later life sleep disturbances was 3.0% (95% CI, 1.8% to 3.8%). The 12 risk factors accounted for 51.9% (32.2% to 68.0%) of dementia among men and 52.4% (32.5% to 68.7%) among women. Overall, the combined PAF of all risk factors was 49.2% (31.1% to 64.9%), and it increased with age.

Conclusion

Nearly up to 50% of dementia cases in Canada are attributable to 12 modifiable risk factors across the lifespan. Canadian risk reduction strategies should prioritize targeting physical inactivity, hearing loss, obesity, and hypertension.

Playing mahjong is a popular intellectual and social leisure activity in Asian countries. It is culturally believed that this activity is beneficial to cognitive and psychological functioning in older adults. However, empirical evidence of the benefits of playing mahjong is scant and scattered across the Western and Asian literature. This scoping review comprehensively examined previous studies of the relationships between playing mahjong and cognitive, psychological, and functional abilities in older adults, highlighted gaps in the literature, and identified directions for future research. A systematic search of the literature was conducted across thirteen Western and Asian databases. Fifty-three studies, including forty-seven observational and six intervention studies, were identified. Overall, the results of the observational studies suggested that more mahjong-playing experience was associated with better cognitive, psychological, and functional abilities. As an intervention, playing mahjong was found to enhance general cognitive abilities and short-term memory and relieve depressive symptoms. However, because most of the reviewed studies adopted a correlational methodology, the neural mechanism underlying the benefits of playing mahjong awaits further elucidation. The findings of this review suggest that more randomized controlled trials should be conducted to explore the effects of playing mahjong on higher-level cognitive functioning in older populations.

Digital health technologies offer valuable advantages to dementia researchers and clinicians as screening tools, diagnostic aids, and monitoring instruments. To support the use and advancement of these resources, a comprehensive overview of the current technological landscape is essential. A multi-stakeholder working group, convened by the Digital Medicine Society (DiMe), conducted a landscape review to identify digital health technologies for Alzheimer’s disease and related dementia populations. We searched studies indexed in PubMed, Embase, and APA PsycInfo to identify manuscripts published between May 2003 to May 2023 reporting analytical validation, clinical validation, or usability/feasibility results for relevant digital health technologies. Additional technologies were identified through community outreach. We collated peer-reviewed manuscripts, poster presentations, or regulatory documents for 106 different technologies for Alzheimer’s disease and related dementia assessment covering diverse populations such as Lewy Body, vascular dementias, frontotemporal dementias, and all severities of Alzheimer’s disease. Wearable sensors represent 32% of included technologies, non-wearables 61%, and technologies with components of both account for the remaining 7%. Neurocognition is the most prevalent concept of interest, followed by physical activity and sleep. Clinical validation is reported in 69% of evidence, analytical validation in 34%, and usability/feasibility in 20% (not mutually exclusive). These findings provide clinicians and researchers a landscape overview describing the range of technologies for assessing Alzheimer’s disease and related dementias. A living library of technologies is presented for the clinical and research communities which will keep findings up-to-date as the field develops.