Alzheimer Disease & Associated Disorders最新文献

Purpose: We aimed to examine the clinical characteristics of US veterans who underwent neurocognitive test score-based assessments of Alzheimer disease (AD) stage in the Veterans Affairs Healthcare System (VAHS).

Methods: Test dates for specific stages of AD were referenced as index dates to study behavioral and psychological symptoms of dementia (BPSD) and other patient characteristics related to utilization/work-up and time to death.

Patients: We identified veterans with AD and neurocognitive evaluations using the VAHS Electronic Health Record (EHR).

Results: Anxiety and sleep disorders/disturbances were the most documented BPSDs across all AD severity stages. Magnetic resonance imaging, neurology and psychiatry consultations, and neuropsychiatric evaluations were slightly higher in veterans with mild AD than in those at later stages. The overall average time to death from the first AD severity record was 5 years for mild and 4 years for moderate/severe AD.

Conclusion: We found differences in clinical symptoms, healthcare utilization, and survival among the mild, moderate, and severe stages of AD. These differences are limited by the low documentation of BPSDs among veterans with test score-based AD stages. These data support the hypothesis that our cohorts represent coherent subgroups of patients with AD based on disease severity.

Objective: Episodes of lucidity (ELs), characterized by spontaneous, transient recovery of abilities, are reported across neurological conditions, including advanced dementia. Despite the significance of these events, existing research is limited to retrospective reports. Approaches to prospectively capturing and characterizing ELs in dementia are lacking.

Methods: This pilot study determined the feasibility and acceptability of a multifaceted observational protocol to capture, characterize, and validate ELs in individuals with advanced dementia in hospice. Feasibility was measured through enrollment/retention rates, workload/usability assessment of video observation, and data processing procedures to facilitate the measurement of verbal and nonverbal features for EL characterization. The acceptability of observation and informant validation procedures was qualitatively examined with clinician and family caregiver participants.

Results: Study procedures were endorsed as highly acceptable among clinician (N = 49) and caregiver (N = 16) participants, demonstrating higher than anticipated thresholds for observation duration. Enrollment and retention rates for patient participants (N = 6) were 100% and 84%, respectively. Workload and usability measures demonstrated low disruptiveness and high ease of use after training.

Discussion: Longitudinal video observation among individuals with advanced dementia in hospice care for the detection of lucidity was feasible and highly acceptable. Multidimensional, temporal coding of features of ELs is feasible but time-intensive.

Background: Blood-brain barrier (BBB) dysfunction is emerging as an important pathophysiologic factor in Alzheimer disease (AD). Cerebrospinal fluid (CSF) platelet-derived growth factor receptor-β (PDGFRβ) is a biomarker of BBB pericyte injury and has been implicated in cognitive impairment and AD.

Methods: We aimed to study CSF PDGFRβ protein levels, along with CSF biomarkers of brain amyloidosis and tau pathology in a well-characterized population of cognitively unimpaired individuals and correlated CSF findings with amyloid-PET positivity. We performed an institutional review board (IRB)-approved cross-sectional analysis of a prospectively enrolled cohort of 36 cognitively normal volunteers with available CSF, Pittsburgh compound B PET/CT, Mini-Mental State Exam score, Global Deterioration Scale, and known apolipoprotein E ( APOE ) ε4 status.

Results: Thirty-six subjects were included. Mean age was 63.3 years; 31 of 36 were female, 6 of 36 were amyloid-PET-positive and 12 of 36 were APOE ε4 carriers. We found a moderate positive correlation between CSF PDGFRβ and both total Tau (r=0.45, P =0.006) and phosphorylated Tau 181 (r=0.51, P =0.002). CSF PDGFRβ levels were not associated with either the CSF Aβ42 or the amyloid-PET.

Conclusions: We demonstrated a moderate positive correlation between PDGFRβ and both total Tau and phosphorylated Tau 181 in cognitively normal individuals. Our data support the hypothesis that BBB dysfunction represents an important early pathophysiologic step in AD, warranting larger prospective studies.

Trial registration: ClinicalTrials.gov Identifier: NCT00094939.

Background: Identifying potentially modifiable risk factors associated with MCI in different ethnoracial groups could reduce MCI burden and health inequity in the population.

Methods: Among 2845 adults aged 65+ years, we investigated potential risk exposures including education, physical and mental health, lifestyle, and sensory function, and their cross-sectional associations with MCI. We compared proportions of exposures between Black and White participants and explored relationships among race, MCI, and exposures. Logistic regression modeled MCI as a function of each exposure in the overall sample adjusting for age, sex, educational level, and race, and investigating race*exposure interactions.

Results: Compared with White participants, Black participants had greater odds of MCI (OR 1.53; 95% CI, 1.13 to 2.06) and were more likely to report depressive symptoms, diabetes, and stroke, to have high blood pressure and BMI, and to be APOE - 4 carriers. Exposures associated with higher odds of MCI were diabetes, stroke, lifetime smoking, sleep disturbances, social isolation, loneliness, depression and anxiety symptoms, and vision and hearing loss. There were no significant interactions between race and any exposure.

Conclusions: Black participants had 53% higher odds of MCI adjusting for age, sex, and education. The same exposures were associated with MCI in Black and White participants.

Background: We examined drivers of self and study partner reports of memory loss in mild cognitive impairment (MCI) from Alzheimer (AD-MCI) and vascular disease (Va-MCI).

Methods: We performed retrospective cross-sectional analyses of participants with AD-MCI (n=2874) and Va-MCI (n=376) from the National Alzheimer Coordinating Center data set. Statistical analysis utilized 2-sided t test or the Fisher exact test.

Results: Compared with AD-MCI, Va-MCI subjects (24.5% vs. 19.7%, P =0.031) and study partners (31.4% vs. 21.6%, P <0.0001) were more likely to deny memory loss. Black/African Americans were disproportionately represented in the group denying memory loss in AD-MCI (20.0% vs. 13.2%, P <0.0001) and Va-MCI (33.7% vs. 18.0%, P =0.0022). Study partners of participants with these features also disproportionately denied memory loss: female (AD-MCI: 60.1% vs. 51.7%, P =0.0002; Va-MCI: 70.3% vs. 52.3%, P =0.0011), Black/African American (AD-MCI: 23.5% vs. 11.98%, P <0.0001; Va-MCI: 48.8% vs. 26.5%, P =0.0002), and <16 years of education (AD-MCI only: 33.9% vs. 16.3%, P =0.0262). In AD-MCI and Va-MCI, participants with anxiety were disproportionately represented in the group endorsing memory loss (AD: 28.2% vs. 17.4%, P <0.0001; Va: 31.5% vs. 16.1%, P =0.0071), with analogous results with depression.

Conclusion: The findings would suggest extra vigilance in interview-based MCI detection of persons at-risk for self-based or informant-based misreport.

Objective: Most prior research on physical activity (PA) and cognition is based on predominantly white cohorts and focused on associations of PA with mean (average) cognition versus the distribution of cognition. Quantile regression offers a novel way to quantify how PA affects cognition across the entire distribution.

Methods: The Kaiser Healthy Aging and Diverse Life Experiences study includes 30% white, 19% black, 25% Asian, and 26% Latinx adults age 65+ living in Northern California (n = 1600). The frequency of light or heavy PA was summarized as 2 continuous variables. Outcomes were z-scored executive function, semantic memory, and verbal episodic memory. We tested associations of PA with mean cognition using linear regression and used quantile regression to estimate the association of PA with the 10th-90th percentiles of cognitive scores.

Results: Higher levels of PA were associated with higher mean semantic memory (b = 0.10; 95% CI: 0.06, 0.14) and executive function (b = 0.05; 95% CI: 0.01, 0.09). Associations of PA across all 3 cognitive domains were stronger at low quantiles of cognition.

Conclusion: PA is associated with cognition in this racially/ethnically diverse sample and may have larger benefits for individuals with low cognitive scores, who are most vulnerable to dementia.

Background: The gut microbiome is a complex system within the human gastrointestinal tract. The bacteria play a significant role in human health, and some can promote inflammation and pathologic processes through chemical interactions or metabolites. Gut microbiome dysbiosis has been linked to some neurological and other diseases. Here we aimed to examine microbiome differences between patients with a progressive neurological disorder, idiopathic normal pressure hydrocephalus (iNPH), compared with healthy controls (CO).

Methods: We recruited 37 neurologically healthy CO and 10 patients with shunted iNPH. We evaluated these participants' cognition using the CERAD-NB test battery and CDR test, and collected a variety of information, including about dietary habits and health. We also collected fecal samples, which were subjected to 16S amplicon sequencing to analyze differences in gut microbiome composition.

Results: We found that the iNPH group exhibited significantly different abundances of 10 bacterial genera compared with the CO group. The Escherichia/Shigella and Anaeromassilibacillus genera were most remarkably increased. Other increased genera were Butyrivibrio , Duncaniella , and an unidentified genus. The decreased genera were Agathobaculum , Paramuribaculum , Catenibacterium , and 2 unidentified genera.

Conclusions: Here we report the first identified microbiome differences in iNPH patients compared with healthy controls.

Introduction: Enrolling individuals from underrepresented ethnoracial groups in aging research is often a challenge.

Methods: We sought a diverse sample of older adults from a small-town area for a longitudinal aging study. We employed an intensive community engagement approach encompassing a range of recruitment strategies.

Results: Over 4 years a steady trickle of individuals, 66% self-identifying as Black, signed up for study information; the proportion of those who eventually enroll in the study has been rising each year, from 68% to 94%. Community events, word-of-mouth referrals, and mailed postcards brought in the most contacts. The highest percentage of contacts who ultimately enrolled were from postcards, flyers, and word-of-mouth. Significantly more word-of-mouth referrals were endorsed by Black individuals than White and by Black men than other race/sex groups.

Conclusions: We have had some success in building relationships and trust with the local community, enrolling Black study participants in a proportion equal to their representation in the target community using a variety of recruitment methods. Patience, immersion in the community, and partnerships with key community members alongside traditional advertisements, and the utilization of study participants as recruiters are critical to designing optimal, targeted, recruitment strategies.

Background: Persons living with Alzheimer disease and related dementia (ADRD) in nursing homes (NH) are often excluded from conversations about their health/safety. These omissions impinge on personhood and the rights to have care preferences heard and honored. While persons with ADRD maintain the ability to communicate their preferences long after their decision-making abilities are affected, little is known about how persons with ADRD understand the risks associated with their preferences.

Methods: As part of a larger focused ethnography, in-depth interviews and an adapted risk propensity questionnaire explored the risk perceptions of NH residents with ADRD (N=7) associated with their preferences for care and activities of daily living.

Results: Residents generally self-identified as risk avoiders ( M =3.2±1.84) on the risk propensity scale and were able to rate risk associated with preferences described within 5 thematic categories: 1) participation in decision-making, 2) risk awareness, 3) paying attention to safety, 4) reliance on nursing home staff and family, and 5) impacts on quality of life and quality of care.

Discussion: Results suggest NH residents with ADRD can express risk surrounding their preferences and should be encouraged to participate in discussions about their health and safety.

Objective: The aim of this study was to test whether patients are better oriented to the day on the first working day following the weekend (in Israel-Sunday), compared with other weekdays, on the Mini-Mental Score Examination (MMSE).

Methods: All MMSE scores from November 2016 until December 2022 in our mental health center's computerized system were collected. The proportion of correct answers to orientation to the day was compared between weekdays.

Results: The cohort consisted of 2049 MMSEs taken by 1376 patients [average age 80.3 (SD=9.3), 56.4% female]. The difference between the proportion of correct and incorrect answers was statistically significant between the days, of which Sundays showed a larger difference (53.4%) compared with the other days (χ 2 =20.77, P <0.001, Cramer V =0.104). A statistically significant odds ratio (OR) for providing a correct response was found for Sundays (OR=1.55, P =0.001) and, to a lesser extent, on Thursdays (OR=1.29, P =0.01). The difference between Sundays and other weekdays disappears as the total MMSE decreases.

Conclusion: Day orientation on the MMSE may be better on the first day following the weekend, especially in early cognitive decline.

Clinical implications: The weekday in which the MMSE is performed may influence its results.