Journal of Alzheimer's Disease最新文献

Background: Mild cognitive impairment (MCI) is an important prodromal stage of Alzheimer's disease (AD), affecting 69 million individuals worldwide. At present, there is a lack of a community-applicable tool for MCI screening. Exhaled breath volatile organic compounds (VOCs) have been used to distinguish MCI from cognitively normal (CN) individuals only in small sample size studies and the efficacy has not been compared with blood biomarkers.

Objective: This diagnostic study aimed to assess the feasibility of using exhaled breath VOCs detection by a portable micro-gas chromatography (μGC) device as a screening tool to discriminate MCI from CN individuals in a community population.

Methods: A detection model was developed and optimized from five distinct machine learning algorithms based on the differential VOCs between 240 MCI and 241 CN individuals. Among these 481 participants, five plasma biomarkers were measured in 397 individuals (166 MCI and 231 CN).

Results: The final model (481 individuals) incorporating eight differential VOCs showed good performance with an area under the receiver-operating characteristic curve (AUC) of 0.84 (95% confidence interval (95% CI): 0.83-0.85). The AUC of the VOC model (0.80, 95% CI: 0.69-0.90) was higher than that of the plasma model (0.77, 95% CI: 0.65-0.88) (397 individuals).

Conclusions: The detection of exhaled breath VOCs by a portable μGC device is feasible for MCI screening in community populations, potentially facilitating early detection and intervention strategies for individuals at high risk.

We argue that the provision of substantial dietary modifications to individuals who wish to maximize their brain health is ethically permitted, despite evidence for such an intervention being not yet fully conclusive. However, we argue that for a burdensome therapy with weak evidence and potential harms, balanced communication, informed consent and follow-up are necessary components of the ethical provision of such lifestyle changes. Moreover, health should be discussed as a value with individuals alongside non-health priorities to achieve balance and avoid brain healthism.

Background: Differentiating neurodegenerative diseases can be difficult in the clinical setting. This study examines the overlap of diagnostic criteria between frontotemporal dementia (FTD) syndromes with parkinsonism [e.g., corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), behavioral variant frontotemporal dementia (bvFTD)] and Parkinson's disease (PD).

Objective: To explore the diagnostic overlap in patients with FTD syndromes with parkinsonism and PD.

Methods: Patient records from 2751 individuals at a tertiary neurological care center were reviewed, resulting in 112 bvFTD, 38 PSP, and 15 CBS patients. Clinical features and diagnostic criteria fulfillment were assessed.

Results: Significant overlap in diagnostic criteria fulfilment was found: 42 bvFTD and 22 PSP patients met possible CBS criteria, 6 bvFTD patients met possible PSP criteria, and 4 met criteria for all three conditions. Higher cerebrospinal fluid levels of phosphorylated tau and tau were observed in the bvFTD group compared to PSP (p = 0.009, p = 0.002). The Mini-Mental State Examination score also differed between bvFTD and PSP (p = 0.020), and between PSP and CBS (p = 0.047). Neuroimaging showed substantial heterogeneity.

Conclusions: The study reveals significant overlap in diagnostic criteria among FTD syndromes with parkinsonism, underscoring the need for more precise diagnostic criteria. Improved biomarkers could support differential diagnosis and enhance clinical trial design. Common cerebrospinal fluid biomarkers used in Alzheimer's disease diagnostics may provide additional support in the differential diagnosis.

Background: Leisure activity and sleep time are key factors in cognitive impairment, but the impact of their long-term trajectories on incident cognitive impairment remains unclear.

Objective: To examine the association of leisure activity trajectories, sleep time trajectories and their combined effects with incident cognitive impairment in older adults.

Methods: Data from the Chinese Longitudinal Healthy Longevity Survey (2008-2018) were analyzed, including adults aged ≥65 who participated in at least three surveys. Group-based trajectory modeling explored leisure activity and sleep time patterns. Cox proportional-hazards regression model assessed the association of leisure activity trajectories and sleep time trajectories and their combined effects with incident cognitive impairment.

Results: We included 3094 participants with a median follow-up of 6.07 years. The optimal trajectory groups for leisure activity and sleep time were four and three, respectively. The low-level leisure activity group were associated with an increased risk of cognitive impairment (HR, 95%CI: 2.07, 1.37-3.13), whereas the high-level leisure activity group were associated with a reduced risk of cognitive impairment (HR, 95%CI: 0.60, 0.36-0.99). Short sleep time group was associated with a reduced risk of cognitive impairment (HR, 95%CI: 0.62, 0.41-0.92). In the combined effect, leisure activity belonging to the low-level group and sleep time belonging to the moderate sleep time group or the long sleep time group were associated with an increased risk of cognitive impairment.

Conclusions: Long-term high-level leisure activity and short sleep time are associated with a reduced risk of cognitive impairment in older adults.

Anosognosia, a lack of self-awareness regarding cognitive dysfunction, often accompanies the progression of Alzheimer's disease (AD) pathology. This study explored the relationship between AD pathology and anosognosia measured by discrepancies in Cognitive Function Instrument (CFI) scores, as rated by participants and their study partners (SP). Using mixed-effects models on non-demented participant data, the results revealed that lower self-reported CFI score compared to SP ratings was significantly associated with positive amyloid PET results (odds ratio 1.081 per-1 decrease in ΔCFI). Our findings suggest that CFI-based anosognosia could serve as a potential predictor of positive amyloid PET status.

Background: The clinical significance of enlarged perivascular spaces (EPVS) in Alzheimer' s disease (AD) was ambiguous.

Objective: To investigate whether EPVS contribute to blood-brain barrier (BBB) leakage and cognition in AD.

Methods: The study included a total of 64 participants (26 healthy controls and 38 patients with AD). The evaluation of EPVS and BBB permeability was performed in specific anatomical locations: the centrum semiovale (CSO), basal ganglia, and hippocampus. The EPVS ratings were performed according to Potter's instructions. BBB permeability was evaluated using dynamic contrast-enhanced-MRI. The relationship between EPVS and global cognition (Mini-Mental State Examination and Montreal Cognitive Assessment), cognitive subdomains, and BBB permeability were examined in both groups. Finally, the relationship between CSO BBB permeability and cognition in AD patients was investigated.

Results: High-grade CSO EPVS was found associated with AD (OR: 3.40, 95% CI: 1.11-11.90, p = 0.04). In the AD group, a significant correlation was observed between high-grade CSO EPVS and lower MMSE score (r = -0.36, p = 0.03) and verbal fluency (r = -0.44, p = 0.01). High-grade CSO EPVS positively correlated with BBB leakage (r = 0.58, p < 0.001). The BBB permeability of CSO negatively correlated with verbal fluency (r = -0.52, p < 0.001) and attention (r = -0.40, p = 0.01).

Conclusions: High-grade CSO EPVS is related to BBB leakage, which contributes to cognitive impairment in AD patients, especially verbal frequency. CSO EPVS can function as a convenient AD marker for intervention and therapy.

Background: Dementia impacts individuals, families, and society, necessitating effective prevention strategies.

Objective: To evaluate the feasibility of a community-adapted multi-domain intervention for dementia prevention among older adults in Obu City, Japan and how uncertainties in implementing definitive trials can be reduced.

Methods: A 12-month one-arm intervention trial was conducted with 80 community-dwelling older adults aged 65-86 years from two district regions. The multi-domain intervention included physical exercise, nutrition guidance, cognitive training, social participation, and vascular risk management. The primary outcome was the continuation rate, defined as the proportion of participants attending >60% of classes from the initial assessment to 6 months. Secondary outcomes, such as fidelity, acceptability, and appropriateness, were assessed through qualitative and quantitative evaluations. Additionally, health outcomes, including cognitive function and overall lifestyle, were evaluated.

Results: The study achieved continuation rates of 75% and 76% at 6 and 12 months, respectively, indicating high feasibility. Participants showed high program acceptability (average acceptance score, 4.4 of 5). Fidelity was high regarding content coverage and duration, although the frequency and coverage varied between study sites. Cognitive function remained stable; food-diversity status improved significantly over the study period, though the absence of a control group limits causal interpretation of these changes.

Conclusions: The community-adapted multi-domain intervention for dementia prevention demonstrated high feasibility and acceptability among older adults. Our findings can help reduce uncertainties and support planning future definitive trials to evaluate the effectiveness of community-based dementia-prevention programs.

Despite growing awareness that disclosing biomarker results to research participants is aligned with ethical principles of researcher-participant partnership, there are currently no widely adopted guidelines for this disclosure in Alzheimer's disease research. We developed a process and tools to deliver biomarker and genetic results to 65 participants of The Memory and Aging Study of the Duke-UNC Alzheimer's Disease Research Center (ADRC). Survey responses of 46 participants were analyzed. We show high participant satisfaction and lower anxiety levels after receiving the results. The developed process and materials provide a template for standardized Alzheimer's disease biomarker result delivery in the research setting.

Background: Hearing loss (HL) of moderate or higher grades is common in older adults with increasing prevalence as people age, rising from 12% at the age of 60 years to over 58% at 90 years. HL in midlife is one of the main potentially modifiable risk factors for dementia. It is estimated that 7% of dementia cases globally could be avoided if this risk factor was eliminated. However, much of the research conducted has been in high-income countries even though low- and middle-income countries have the highest prevalence of dementia.

Objective: To study the association between HL and cognitive decline during eight years of follow-up in a Brazilian sample.

Methods: Participants from the São Paulo center of the Brazilian Longitudinal Study of Adult Health were evaluated in three study waves (2008-10, 2012-14, and 2017-19). HL was defined as pure-tone audiometry above 25 dB in the better ear. Cognitive performance was evaluated with six tests related to memory, verbal fluency, and trail-making tests. A global cognitive z-score was derived from these tests. The association between HL and cognitive decline was evaluated with linear mixed-effects models adjusted for sociodemographic, lifestyle, and clinical factors.

Results: Of 805 participants (mean age 51 ± 9 years, 52% women, 60% White), 62 had HL. During follow-up, HL was associated with faster global cognitive decline (β = -0.012, 95% CI = -0.023; 0.000, p = 0.039).

Conclusions: HL was significantly associated with a faster rate of global cognitive decline after a median follow-up of eight years in a sample of middle-income country.

Background: Given the limited effective treatments for Alzheimer's disease (AD), obesity and serum uric acid (SUA) levels which are considered modifiable risk factors for dementia are of interest. However, research indicates conflicting results.

Objective: We aimed to further investigate the association of body weight (BW) and SUA with AD biomarkers and cognitive impairment.

Methods: Clinical data were collected from 139 adults (mean age 66.9 years) with chronic cognitive impairment. Cerebrospinal fluid (CSF) biomarkers and PET imaging were used to assess amyloid-β (A) and Tau (T) tangles load, classifying participants into AT profiles based on the results. The association of BW and SUA with AT profiles was evaluated using multivariable logistic regression, and their relationship with cognitive function (Mini-Mental State Examination (MMSE) scores) were analyzed using multivariable linear regression.

Results: Lower BW levels significantly influenced the presence of Aβ positive state (A+) (p = 0.007), while SUA levels did not (p = 0.263). Higher dementia proportion (p = 0.021), lighter BW (p = 0.019), and lower mean arterial pressure (MAP) levels (p = 0.025) were associated with AD pathological progress (A-T-→A+T-→A+T+), but SUA was not observed statistically significant. Among all participants regardless of Aβ state, high education levels (p < 0.001), high BW (p = 0.010), and high SUA (p=0.036) were associated with high MMSE scores, and high serum creatinine (p = 0.003) was associated with low MMSE scores.

Conclusions: Lower BW may accelerate AD pathology and cause cognitive impairment, while SUA is not linked to AD pathological progression but protects cognitive function.