National Center for Geriatrics and Gerontology

In recent years, plasma levels of phosphorylated tau species, particularly p-tau217, have emerged as reliable indicators of amyloid-β (Aβ) pathology in the brain. However, real-world data on plasma biomarkers across diverse populations remain limited. We conducted a prospective multicenter study under real-world clinical settings to evaluate diagnostic performance of plasma biomarkers, including p-tau217, in discriminating amyloid status among a Japanese population. A total of 332 participants were recruited from seven memory clinics across Japan. Participants were categorized into four clinical subgroups: cognitively unimpaired (CU), mild cognitive impairment (MCI), Alzheimer’s disease dementia (ADD), and non-ADD. We measured Aβ40, Aβ42, p-tau181, total-tau, and neurofilament light chain (NfL) in CSF and Aβ40, Aβ42, p-tau217, p-tau181, glial fibrillary acidic protein (GFAP) and NfL in plasma using the LUMIPULSE platform. Amyloid status was determined by amyloid PET imaging and/or CSF Aβ42/40 ratio. Significant differences were observed in plasma biomarker levels, including Aβ42/40, p-tau217, p-tau181, GFAP, and NfL across clinical categories. Plasma p-tau217 and p-tau217/Aβ42 achieved high diagnostic accuracy, with areas under the curve (AUC) exceeding 0.9 with PET amyloid status as the reference, demonstrating comparable performance to the in vitro diagnostic (IVD)-approved CSF Aβ42/40 ratio. The two-cutoff approach using plasma p-tau217 and p-tau217/Aβ42 to achieve 90% sensitivity and 90% specificity provided high negative and positive predictive values. The intermediate range defined by these two-cutoff points was narrower for p-tau217/Aβ42 than for p-tau217. The predefined U.S. Food and Drug Administration (FDA)-approved two-cutoff points were applicable to this cohort with good accuracy. Concordance of plasma p-tau217 or p-tau217/Aβ42 with PET or CSF Aβ42/40 status ranged from 87% to 93%, although larger discordant results were observed in the non-ADD group. This study demonstrates the clinical utility of plasma p-tau217 and p-tau217/Aβ42 ratio for real-world diagnostic evaluations of dementia. However, careful interpretation of plasma biomarker is warranted in cases showing discordant results with PET or CSF findings.

Understanding digestible energy intake (DEI) and metabolizable energy intake (MEI) is essential for elucidating human energy balance. The absolute of DEI refers to gross energy intake minus fecal energy loss (EL), whereas MEI further accounts for urinary EL. This systematic review aimed to synthesize the findings from studies that utilized bomb calorimetry to measure DEI and/or MEI (PROSPERO CRD42021230982). Medical Literature Analysis and Retrieval System Online (via PubMed), the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and Scopus were searched for articles published between January 1973 and July 2024. Human studies (adults aged ≥18 y) were included without restrictions on study design. Data were descriptively summarized according to dietary conditions, including overeating, undereating, high-fiber diets, tree nut intake, time-restricted eating (TRE), medication use, and disease status. Twenty-three studies were included. Overeating generally increased absolute fecal ELs; however, proportional DEI and MEI remained relatively stable, suggesting adaptive responses. High-fiber diets and tree nut intake consistently lowered the proportions of DEI and MEI, indicating that dietary composition affects energy absorption efficiency. Results for TRE were inconsistent, with 1 study showing increased fecal EL and another reporting no significant changes. Aging and disease, particularly short bowel syndrome and home parenteral nutrition dependence, were associated with markedly reduced proportions of DEI and MEI. Despite methodological variability across studies, this review highlighted that both dietary quantity and composition significantly influence energy absorption. Furthermore, limited evidence suggested that aging and diseases impair energy absorption. Future studies using standardized protocols and randomized controlled trials are warranted to clarify the determinants of DEI and MEI across diverse populations. This study was registered at PROSPERO as CRD42021230982.

Fall risk was highest in older adults with coexisting cognitive impairment and frailty. Frailty alone had minimal impact in cognitively normal individuals, demonstrating a synergistic interaction between cognitive and physical vulnerability.

Based on their ability to analyze methylation differences genome-wide in a large number of samples at a reasonable cost and time, microarrays were rapidly adopted by Alzheimer's disease (AD) researchers to isolate CpG sites with methylation levels that were changed in the blood of AD patients. However, concerns gradually arose about the reproducibility of these methylation markers. I attribute the cause to the lack of confirmation of methylation changes detected by DNA methylation arrays. Only by simply plotting an individual's methylation distribution can some false methylation differences be avoided. Furthermore, we may need to set a realistic, minimum threshold for methylation changes for clinical purposes. The prospect of using DNA methylation as a diagnostic marker for AD may be compromised by the increasing number of irreproducible markers. Therefore, establishing minimum guidelines for the search and presentation of AD-associated methylation markers is necessary when publishing. Some empirically useful guidelines are outlined in this Perspective, and applications for diagnosing AD using reliable methylation markers are also presented. One of the most desired applications of methylation markers will be to identify individuals whose cognitive abilities decline before memory problems appear, a task that has not yet been accomplished with protein markers or imaging.

This study aimed to examine the influence of leisure-time physical activity habits and willingness to engage in physical activity on the onset of depressive symptoms among older adults over a 3-year period. This study included 3341 participants without depressive symptoms who participated in the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes. Leisure-time physical activity habits and willingness to engage in leisure-time physical activity were elicited using a questionnaire, and the participants were classified into (1) habitual, (2) no habit but willing (willing), and (3) no habit and unwilling (unwilling). Outcome was defined as a score of 6 or more on the Geriatrics Depression Scale in a follow-up survey conducted 3 years after the onset of depressive symptoms. Logistic regression analysis was used to examine the effects of habit and willingness on the onset of depressive symptoms. Of the participants (median age 70 years [interquartile range: 66-76 years]; 56.0% were women), 275 (14.1%) developed depressive symptoms. The habitual, willing, and unwilling groups comprised 2879 (87.2%), 246 (7.5%), and 176 (5.3%), respectively. Logistic regression analysis showed that compared to the habit group, the willing group was significantly associated with the onset of depressive symptoms (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.10-2.78), while the unwilling group was not significantly associated with the onset of depressive symptoms (OR 0.99, 95% CI 0.54-1.82). The gap between the willingness to exercise and the lack of a daily habit can increase the risk of depression in older adults.

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

The FR-IC index demonstrated good concurrent validity for baseline disability and significant predictive validity for 1-year deterioration in disability among older outpatients. This tool may enable effective risk stratification and seamless monitoring of physical and mental capacities across the aging trajectory in clinical settings.

Hearing loss in older adults is a risk factor for depression, cognitive decline, frailty, and other conditions, and it has various negative physical and psychological effects. Hearing loss care requires the support of medical professionals; however, most hearing care education is targeted at professionals working in hospitals and care facilities, with few interventions aimed at visiting nurses. To address this gap, we developed the "Hearing Loss Care Education Program for the Older Adults" to improve visiting nurses' skills in managing hearing loss. This study aimed to evaluate the effectiveness of the program. This cluster randomized controlled trial was registered in the UMIN Clinical Trials Registry (UMIN000053337) and conducted across 22 visiting nursing stations: 11 in the intervention group (60 visiting nurses) and 11 in the control group (42 visiting nurses). The intervention consisted of on-demand lectures and technical exercises, followed by a 3-month follow-up period. The primary outcome was the "implementation of hearing care," whereas the secondary outcomes were "knowledge of hearing care" and "confidence in implementing hearing care." Between-group differences were analyzed using generalized estimating equations. As part of the primary outcome, a significant increase in the implementation of "hearing screening" was observed in the intervention group (odds ratio 8.35, 95% confidence interval 3.60-19.34, p < 0.001). Additionally, the intervention group demonstrated significantly higher "knowledge of hearing care" and "confidence in implementing hearing care." These findings suggest that the program effectively enhanced visiting nurses' knowledge and confidence in hearing care and supports the integration of hearing screening into their routine practice.

BackgroundEpileptic seizures and subclinical epileptiform activity are increasingly recognized as comorbidities in Alzheimer's disease (AD) and have been associated with accelerated cognitive decline. Whether antiseizure medication (ASM) therapy favorably influences cognitive trajectories in AD remains unclear.ObjectiveTo assess the effects of ASM therapy on cognitive trajectories in patients with AD with comorbid epilepsy, and to identify patient subgroups most likely to benefit.MethodsWe retrospectively studied 538 patients (403 AD only; 135 AD with comorbid epilepsy) treated with newer-generation ASMs between 2020 and 2025. Cognitive change over 24 months was assessed using the Mini-Mental State Examination (MMSE). Analyses included linear mixed-effects modeling, sliding window interaction analysis across baseline MMSE scores (11-29), and 1:1 propensity score matching stratified by baseline MMSE (≤21, 22-26, and ≥27).ResultsAfter propensity score matching, baseline MMSE scores were well balanced between the groups. The sliding window analysis suggested a subgroup-specific interaction between group and time in the MMSE (range 22-26), peaking at MMSE 25. In the 22-26 stratum, MMSE at 12 months was higher in the AD with comorbid epilepsy group than in the AD-only group (23.23 ± 0.46 versus 20.33 ± 0.52, p < 0.001). The 24-month difference (22.92 ± 1.37 versus 19.36 ± 0.99, p = 0.047) was borderline and considered exploratory.ConclusionsAntiseizure therapy was associated with favorable cognitive trajectories in patients with AD and comorbid epilepsy, particularly with baseline MMSE 22-26. These exploratory findings suggest a potential therapeutic window that warrants confirmation in prospective studies.