Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring最新文献

Introduction: Subjective cognitive complaints often precede declines in objective measures of cognitive performance. Associations of incipient Alzheimer's disease (AD) neuropathology with subjective cognitive complaints may be detectable earlier than associations with neuropsychological testing among cognitively normal individuals.

Methods: We examined the independent associations of positron emission tomography measures of amyloid beta and tau pathologies with longitudinal subjective complaints and memory among 91 cognitively normal Baltimore Longitudinal Study of Aging participants using linear mixed effects models. Subjective complaints and memory performance were assessed with the Cognitive Failures Questionnaire and the California Verbal Learning Test, respectively.

Results: Greater parahippocampal tau, independent of amyloid, was associated with higher subjective complaints (estimate = 0.25, standard error [SE] = 0.1, P = $0.015$ ), while greater entorhinal tau corresponded to an attenuated increase in complaints over time (estimate = -0.06, SE = 0.03, P = $0.047$ ). Hippocampal tau was associated with steeper memory decline (estimate = -0.03, SE = 0.01, P = $0.040$ ).

Conclusion: Subjective cognitive complaints may be a reflection of early cerebral tau pathology in cognitively normal individuals.

Highlights: Greater parahippocampal tau was linked with higher subjective cognitive complaints.Entorhinal tau was associated with slower increases in cognitive complaints over time.Subjective complaints may reflect early amyloid and tau in cognitively normal adults.

Introduction: This study investigated gender differences in cognitive reserve (CR) in subjective cognitive decline (SCD) and examined the impact of gender-CR interaction on the risk of progression to mild cognitive impairment (MCI).

Methods: We enrolled 440 SCD patients and estimated CR using premorbid intelligence (Test di Intelligenza Breve [TIB]). To account for socio-cultural differences, patients were stratified by birth cohort (pre-/post-1950). A Markov random-field (MRF) model explored relationships between gender, CR, education, and age. Logistic regression assessed MCI progression risk.

Results: Women showed lower TIB scores than men (p < 0.001). The MRF model revealed an inverse connection between TIB and female gender, while no link was observed between TIB and generation. Progression to MCI was predicted by age at onset (p < 0.001), apolipoprotein E (APOE) status (p = 0.002), and TIB (p = 0.018), but not gender.

Discussion: Gender has an impact on CR, but not through socio-economic variables. In turn, CR influenced the risk of MCI progression, whereas gender did not.

Highlights: Subjective cognitive decline (SCD) women presented lower cognitive reserve (CR) levels than men, despite similar education levels.Social-cultural factors did not explain these gender differences in CR in SCD.The gender-CR interaction was not mediated by social-cultural factors.The risk of progression to mild cognitive impairment (MCI) was influenced by CR but not by gender.

Introduction: Emerging evidence implicates gut microbiota (GM), shaped by diet, in Alzheimer's disease (AD) pathogenesis. However, the association between the dietary index for GM (DI-GM) and AD remains unclear.

Methods: This cross-sectional study analyzed data from 28,830 adults aged ≥20 years in the 2004-2018 National Health and Nutrition Examination Survey (NHANES). The DI-GM score, derived from dietary recalls, comprised beneficial to GM score (BGMS) and unfavorable to GM score (UGMS) components. AD was identified via self-report, medications, or death certificates. Multivariable weighted logistic regression, restricted cubic spline, and subgroup analyses were performed.

Results: Contrary to expectations, higher DI-GM score and UGMS were associated with increased AD prevalence (DI-GM: odds ratio [OR] = 1.24, 95% CI: 1.02 to 1.52, p = 0.033; UGMS: OR = 1.36, 95% CI: 1.10 to 1.69, p = 0.005).

Discussion: The DI-GM was positively associated with AD prevalence, suggesting that imbalanced plant-based diets low in protein or key nutrients may elevate AD risk despite presumed microbiota benefits.

Highlights: Higher DI-GM and UGMS were significantly associated with greater AD prevalence in US adults.Restricted cubic spline analyses showed linear and non-linear associations of DI-GM and UGMS with AD, respectively.Results challenge prior assumptions that higher DI-GM scores are uniformly linked to health benefits.Imbalanced plant-based diets low in protein or key nutrients may adversely affect cognitive aging despite presumed microbiota benefits.

Introduction: Amyloid positron emission tomography (PET) allows in vivo measurement of amyloid plaque deposition; however, different tracers lead to different results. We test the hypothesis that the variability in amyloid measurements is related to white matter retention, and accounting for this variability can improve agreements.

Methods: Data from the Centiloid project was downloaded and processed for four F18 tracer-to-Pittsburgh Compound B (PiB) pairs to obtain mean cortical standardized uptake value ratio (MCSUVR). Three approaches were examined to account for white matter contribution to the MCSUVR. Pearson's correlation was used to assess the between tracer agreements. Steiger's test was used to determine the significance of improvement.

Results: Accounting for white matter signal improves the agreement. The regional spread function partial volume correction (RSF PVC) method was most consistent in achieving statistically significant improvements (p < 0.05) for all four tracer pairs.

Discussion: Between-tracer agreement of amyloid measure can be improved by accounting for white matter signal. Further investigation is ongoing for additional improvement.

Highlights: Analyzing head-to-head data for all four common F18-labeled tracers against Pittsburgh Compound B (PiB).Evaluating three different techniques to correct for white matter signal.Steiger's test to determine the significance of improvements.White matter uptake contributes to the between-tracer measurement difference.

Background: Dementia, including Alzheimer's disease (AD), is a growing concern in Egypt, yet biomarker research in this population is scarce. Identifying serum biomarkers is essential for early diagnosis and understanding disease mechanisms in underrepresented groups.

Methods: We performed serum proteomic profiling on 20 Egyptian dementia patients and 10 cognitively unimpaired controls from the Egyptian Dementia Registry using mass spectrometry. Differential protein expression and pathway enrichment analyses were conducted.

Results: Of 260 quantified proteins, 21 were significantly different between dementia patients and controls (P < 0.05). Several serine protease inhibitor and immunoglobulin family proteins were downregulated, while apolipoprotein A-II was upregulated in dementia. Enrichment analysis revealed associations with inflammation, complement activation, and lipid metabolism pathways.

Conclusion: This is the first serum proteomic study of dementia in an Egyptian cohort, highlighting coordinated changes in protein families involved in inflammation and lipid metabolism, and emphasizing the importance of biomarker research in diverse populations.

Highlights: The study presents initial proteomic data from the Egyptian Dementia Registry.The Egyptian population has been underrepresented in the area of dementia research.Serine protease inhibitor G1, apolipoprotein A-II, and lipopolysaccharide binding protein emerged as significant proteins.The work lays the foundation for more understanding of molecular determinants in dementia in the Middle East.

Introduction: Research on whether physical activity (PA) is associated with cognition is abundant but very few studies have examined the extent to which prior cognitive ability may account for PA participation in midlife.

Methods: Over 800 men self-reported PA at average ages of 40 and 56. General cognitive ability (GCA) was assessed at an average age of 20. Specific cognitive abilities and GCA were assessed at average ages of 56 and 68. Relationships among age 20 GCA, midlife PA, and cognitive functioning in mid- and late-life were examined with generalized estimating equations.

Results: Age 20 GCA was significantly associated with age 56 leisure metabolic equivalent of energy expenditure (MET)-hours of PA (b = 0.14, p = 0.027). Age 56 leisure MET-hours were positively (b = 0.04, p = 0.021) and age 40 vigorous leisure PA was inversely (b = -0.10, p = 0.012) associated with age 68 GCA (b = 0.04, p = 0.021).

Discussion: There are reciprocal associations between PA and cognitive functioning.

Highlights: Young adult general cognitive ability (GCA) predicts midlife physical activity (PA).Midlife PA and cognition were not associated after adjusting for young adult GCA.Midlife PA is associated with later-life cognition, adjusted for young adult GCA.Work-related PA was inversely associated with later-life cognitive functioning.The relationship between PA and cognitive function is bidirectional.

Introduction: Consistent predictive performance across racial and ethnic groups is essential to the use of plasma biomarkers as screening tools in preclinical Alzheimer's disease trials.

Methods: Logistic regression examined racial and ethnic group differences in plasma eligibility using an algorithm that included Phosphorylated tau217 to non-phosphorylated tau217 ratio, amyloid beta 42/40, age, and apolipoprotein E to predict > 18 Centiloids on amyloid imaging in cognitively unimpaired individuals.

Results: Among 6437 participants screened, with non-Hispanic (NH) White as the reference group, odds ratios of plasma ineligibility were 2.88 (95% confidence interval [CI]: 1.40-6.96) for Hispanic Black, 1.60 (95% CI: 1.33-1.92) for Hispanic White, 2.10 (95% CI: 1.37-3.38) for NH Asian, and 1.59 (95% CI: 1.27-2.0) for NH Black participants. Positron emission tomography (PET) eligibility rates did not differ among those who were plasma eligible.

Discussion: Differential rates of plasma eligibility, but consistent PET eligibility among plasma-eligible participants, were observed, supporting the use of universal biomarker cutpoints across race and ethnic groups.Highlights: Underrepresented racial and ethnic groups had lower rates of plasma eligibility compared to non-Hispanic White individuals based on a plasma screening algorithm that included the phosphorylated tau 217 ratio.Among plasma-eligible participants, amyloid positron emission tomography eligibility rates did not differ by racial and ethnic group.Plasma biomarker tests may provide equivalent effectiveness for identifying imaging biomarker eligible, cognitively unimpaired individuals across racial and ethnic groups.

Introduction: White matter hyperintensities (WMHs) are characteristic of Alzheimer's disease (AD), and cognitive reserve (CR) protects cognitive function. However, whether WMHs mediate the CR-cognition relationship remains unclear.

Methods: Brain imaging, clinical features, and neuropsychological assessments were performed, and CR was measured using the Cognitive Reserve Index questionnaire. Bootstrap mediation analysis examined CR's role in specific cognitive functions, controlling for covariates.

Results: Participants who were cognitively unimpaired (CU; n = 85, mean age = 68.6 ± 5.7) and who had mild cognitive impairment (MCI; n = 43, mean age = 71.8 ± 6.5) or AD (n = 61, mean age = 72.8 ± 6.2) were included. CR was positively associated with global and non-memory cognitive functions in the CU and MCI groups. In the CU group, WMHs served as a mediator between CR and global cognitive ability.

Discussion: CR may maintain the optimal cognitive function by mitigating the WMH burden independently of AD-related brain changes.

Highlights: Cognitive reserve (CR) positively links to non-memory cognition.Cognitive reserve mitigates white matter hyperintensities to preserve cognition.Cognitive reserve primarily protects cognition in pre-Alzheimer's stages.

Introduction: Remote, smartphone-based cognitive assessments such as the Mobile Toolbox (MTB) may increase the accessibility of Alzheimer's disease (AD) clinical trials. We examined the feasibility of the MTB among cognitively unimpaired (CU) older adults and investigated its associations with standardized in-clinic cognitive testing and amyloid and tau positron emission tomography imaging.

Methods: A total of 100 CU older adults self-administered the MTB remotely on their personal devices. Linear regression models correcting for demographics investigated associations of MTB fluid and crystallized cognition composites with in-clinic Preclinical Alzheimer's Cognitive Composite-5 (PACC-5) scores, global amyloid-beta burden and tau deposition in the medial-temporal lobe and neocortex.

Results: Most participants completed the MTB without requiring assistance (81%) or reminders (61%). MTB fluid cognition scores were positively associated with PACC-5 scores and negatively with tau deposition in the medial-temporal lobe and neocortex.

Discussion: These findings suggest that the MTB may provide a feasible approach to capture cognitive processes relevant in preclinical AD.

Highlights: The Mobile Toolbox (MTB) is a remote smartphone-based cognitive assessment.We deployed the MTB in CU older adults with Alzheimer's disease (AD) biomarkers.We show how the MTB may facilitate cognitive assessment in preclinical AD research.

Introduction: Sleep disturbances are common in older adults, particularly those with cognitive impairment. This study examines how day-to-day sleep quality impacts real-world driving behaviors, offering insight into sleep as a potential functional biomarker of cognitive health.

Methods: We monitored 149 community-dwelling older adults (90 cognitively impaired, 59 unimpaired) over 12 weeks. Sleep was measured via wrist-worn actigraphy, and driving data were collected via an in-vehicle sensor system. A zero-inflated Poisson regression model examined whether sleep efficiency was associated with next-day driving likelihood and frequency, and whether these relationships varied by cognitive status.

Results: Better sleep efficiency increased the likelihood of driving the next day more for cognitively impaired participants than for unimpaired participants. Higher sleep efficiency was associated with increased driving frequency in both groups.

Discussion: These findings underscore the importance of daily sleep variability as a potential digital biomarker for functional abilities in older adults, highlighting opportunities for early intervention to preserve mobility and independence.

Highlights: A 1 standard deviation increase in sleep efficiency increases next-day trip counts (incidence rate ratio = 1.014).In cognitively impaired participants, better sleep lowers the odds of not driving the next day (odds ratio = 0.877).Among those who choose to drive, trip counts do not differ by cognitive status.