bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of herpes zoster vaccination on the occurrence of deaths due to dementia in England and Wales
Authors: Michalik Felix , Xie Min , Eyting Markus , Hess Simon , Chung Seunghun , Geldsetzer Pascal 
Published: January 2025

AbstractBackgroundUsing a unique natural randomization, we have recently provided evidence from Welsh electronic health record data that herpes zoster (HZ) vaccination caused a reduction in new dementia diagnoses over a seven‐year period. This study aimed to determine whether eligibility for HZ vaccination also caused a reduction in deaths due to dementia in England and Wales over a nine‐year follow‐up period.MethodsAdults who had their 80th birthday shortly before September 1 2013 were ineligible for free HZ vaccination and remained ineligible for life, whereas those who had their 80th birthday shortly after September 1 2013 (i.e., born on or after September 2 1933) were eligible for one year. This date‐of‐birth threshold generated birth cohorts who are likely exchangeable in observed and unobserved characteristics except for a small difference in age and a large difference in HZ vaccination uptake. We used country‐wide data from death certificates in England and Wales on underlying causes of death from September 1 2004 to August 31 2022 by ICD‐10 code and month of birth. Our analysis compared the percentage of the population with a death due to dementia among the month‐of‐birth cohorts around the September 2 1933 eligibility threshold using a regression discontinuity design.ResultsThe study population included 5,077,426 adults born between September 1 1925 and August 31 1941 who were alive at the start of the HZ vaccination program. We estimated that over a nine‐year follow‐up period, eligibility for HZ vaccination reduced the percentage of the population with a death due to dementia by 0.38 (95% CI: 0.08 to 0.68, p = 0.012) percentage points, corresponding to a relative reduction of 4.8%. As in our prior analysis, this effect was stronger among women (‐0.62 [95% CI: ‐1.06 to ‐0.19] percentage points, p = 0.004) than among men (‐0.11 [95% CI: ‐0.51 to 0.28] percentage points, p = 0.574).ConclusionsOur findings indicate that HZ vaccination reduced cognitive decline at a fairly advanced stage of the dementia disease process because most individuals whose underlying cause of death was dementia during our nine‐year follow‐up period were likely already living with dementia at the start of the HZ vaccination program.
White matter microstructure and cognition in the Alzheimer’s Disease Connectome Project (ADCP)
Authors: Roberts John Weston , Adluru Nagesh , Nair Veena A. , Adluru Anusha , Nencka Andrew S , Li Shi‐Jiang , Davidson Richard J , Okonkwo Ozioma C , Alexander Andrew L , Bendlin Barbara B. , Prabhakaran Vivek 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) has been mainly thought of as a disease involving gray matter changes. However, despite known correlations between white matter integrity and cognition, less is known about how disruptions to white matter during the development of AD underpin cognitive impairment. This study tests the associations between disruptions to white matter along the AD clinical continuum (cognitive unimpaired (CU): cognitive impaired (CI) – Mild Cognitive Impairment (MCI) and AD) and cognition using diffusion tensor imaging (DTI) and multi‐tissue neurite and orientation dispersion and density imaging (mtNODDI) models of the multi‐shell connectome diffusion MRI (ms‐dMRI) data from the Alzheimer’s Disease Connectome Project (ADCP).MethodMulti‐shell connectome diffusion MRI data from 80 participants (55 CU (32 F, mean age 66.7 +/‐ 6.6; 25 CI (8 F, mean age 73.6 +/‐ 7.3)) in the ADCP were pre‐processed using DESIGNER processing guidelines. Cognition was assessed using the Cognition Total Composite score from the NIH toolbox. Permutation testing was performed using threshold free cluster enhancement and family wise error correction (FWE) and 10,000 permutations. Relationships between cognitive impairment and white matter integrity were deemed statistically significant for FWE corrected p < 0.05. All analyses controlled for age and sex.ResultOur analysis revealed a significant interaction between clinical status and cognitive test outcomes on the mtODI (multi‐tissue orientation dispersion index) metric, with higher mtODI levels indicating increased neurodegeneration. CU individuals exhibited higher cognitive performance with lower mtODI levels in cerebellar and brainstem regions, whereas CI individuals showed consistently higher mtODI levels in these regions and lower cognitive performance (Figure 1). Moreover, CI individuals presented with lower overall cognitive test scores compared to their CU counterparts. Analysis of clusters uncorrected for multiple comparisons revealed trend‐level differences in frontal and temporal regions (Figures 2‐3).ConclusionResults demonstrate that CI individuals who perform worse than CU individuals on cognitive tests also have higher levels of neurodegeneration than CU individuals. Further research is needed to replicate and extend these findings to other tests of cognitive ability, and to help better understand the potential links between cognitive decline in AD with white matter integrity of cerebellar and brainstem regions.
APOE‐ε4 is associated with poor sleep and structural differences of the hypothalamus in the PREVENT‐Dementia and ALFA cohort studies
Authors: Laurell Axel AS , Mak Elijah , Underwood Benjamin R , Dauvilliers Yves , Ritchie Craig W , Koychev Ivan , Lawlor Brian A , Naci Lorina , Malhotra Paresh , Grau‐Rivera Oriol , Gispert Juan Domingo , O'Brien John T 
Published: January 2025

AbstractBackgroundSleep disturbances have been identified as a risk factor for developing dementia. The hypothalamus is involved in sleep regulation and may be affected early by neurodegeneration. Our aim was to investigate the relationship between subjective sleep and hypothalamic structure in adults at higher risk of developing dementia.MethodWe analysed baseline data from PREVENT‐Dementia (n=700) and ALFA (n=1478), which are prospective cohort studies of cognitively healthy, middle‐aged participants, who were stratified by apolipoprotein E (APOE) genotype for their risk of dementia. Subjective sleep data was collected using the Pittsburgh Sleep Quality Index (PSQI), including the following components: sleep quality, latency, duration and efficiency. The volumes of five hypothalamic subunits were extracted by automatic segmentation of T1‐weighted 3T MRI images using Freesurfer (version 7.2.0). Combat harmonisation was used to account for using multiple MRI scanners. The data was analysed in R Studio using robust linear and logistic regression, correcting for age, sex, depression, total intracranial volume and multiple comparisons.ResultThe ALFA cohort was significantly older than PREVENT‐Dementia (mean 60 versus 51 years, p<0.001). In the combined datasets, APOE‐ε4 homozygotes had a larger anterior‐superior hypothalamus compared to heterozygotes (p=0.02) and non‐carriers (p=0.02). Furthermore, APOE genotype moderated the association between age and volume of the anterior‐superior hypothalamus (p=0.02), such that APOE‐ε4 carriers had smaller volume with age (homozygotes: m=‐0.19, p=0.14; heterozygotes: m=‐0.17, p<0.01) compared with non‐carriers (m=‐0.10, p<0.01). Long sleep latency was associated with a smaller anterior‐inferior hypothalamus (p=0.05). Sleep latency also moderated the relationship between age and the volume of the anterior‐inferior hypothalamus (p=0.04). While subjects with short sleep latency showed a positive correlation between larger volume and age (m=0.06, p=0.07), there were no correlation with age in those with long sleep latency (m=‐0.01, p=0.91). In the ALFA cohort only, APOE‐ε4 carriers had longer sleep latency than non‐carriers (p=0.02).ConclusionAPOE‐ε4 carriers have a larger anterior‐superior hypothalamus and worse sleep, which may be due to early pathological processes. Our findings underscore the role of the hypothalamus in sleep homeostasis and suggest that involvement of subcortical structures may relate to early symptoms in individuals at risk of dementia.
Graphical indices of brain aging
Authors: Furlano Carmensita , Gareri Pietro 
Published: January 2025

AbstractBackgroundWriting is a cortical function studied by the human science of Graphology, which allows the personal knowledge of the subject, and psychophysical conditions, both in healthy older people and in those affected by dementia. Graphologists and geriatricians can successfully cooperate with this.MethodFive volunteers aged between 60 and 80 years old (3 women and 2 men) were enrolled after signing an informed consent. Each participant underwent multidimensional geriatric evaluation, medical examination, and instrumental exams (Table 1). Each person was asked to write the sentence “I breathe the sweet scent of flowers”, on which Graphological Analysis (in blind) was conducted, based on the evaluation of some variables. Graphology is set up through the neurophysiology of four writing movements: Flexion and Abduction determine the ‘cup’, the Extension prepares the attack of the next letter and its implementation, the Adduction intervenes in the eyelets and in all the gestures of return backwards.ResultIn 4 out of 5 participants, the graphological indices of brain aging were present: slow and heavy writing, a broken, laid or slow rhythm, an uncertain and irregular direction, small superfluous traces, shake, angular and discontinuous movements, the presence of juxtapositions, tremors, disproportions, inequalities in size and deformation of individual letters, tightening of the letters, or high magnification.ConclusionIt is necessary to promote the presence of the Graphologist in the Healthcare fields, by creating local Geriatric Graphology Centers, in collaboration with multidisciplinary teams, where prevention, diagnosis, rehabilitation/therapeutic treatment, study and research activities can be carried out.
Effect of kidney function on plasma pTau217 concentrations using different pTau217 assays
Authors: Algeciras‐Schimnich Alicia 
Published: January 2025

AbstractBackgroundChronic kidney disease (CKD) has been associated with increased plasma phosphorylated Tau217 (pTau217) concentrations, potentially confounding its utility in the evaluation of Alzheimer's disease (AD). We assessed the association of estimated glomerular filtration rate (eGFR) with plasma pTau217 concentrations measured by various assays.MethodWe included 195 participants from the Mayo Clinic Study of Aging or the Alzheimer’s Disease Research Center with diagnoses of cognitively unimpaired (n=114), mild cognitive impairment (n=70), and AD dementia (n=11). Amyloid‐PET was performed with Pittsburgh 11C‐Compound B; abnormal amyloid (A+) was defined as SUVR ≥1.52 (Centiloid ≥25). eGFR was determined based on serum creatinine concentrations. pTau217 was quantified using ALZpath Simoa pTau217 immunoassay, Fujirebio Lumipulse G pTau217(N‐Terminal) immunoassay, and a pTau217 mass spectrometry (MS) assay (C2N Diagnostics). Additionally, a pTau217 ratio (pTau217 to non‐phosphorylated [npTau217]) was calculated using the MS assay. Linear regression was used to assess associations of continuous eGFR with plasma pTau217 and amyloid PET. Differences in mean plasma concentrations between eGFR groups by amyloid PET status were evaluated with one‐way ANOVA tests and associated confidence intervals for each sample mean.ResultMedian pTau217 concentrations in the A+ and A‐ groups were higher in individuals with eGFR <60 mL/min/1.73 m2 compared to those with eGFR ≥60 in all assays except for the A+ group when using the pTau217/npTau217 ratio. A 10‐unit worsening of eGFR was associated with higher pTau217 mean concentrations as follows: 24% (95% CI, 13‐36%) for C2N pTau217, 16% (9‐24%) for ALZpath pTau217, and 12% (5‐20%) for Lumipulse pTau217. eGFR was not significantly associated with the pTau217/npTau217 ratio or amyloid‐PET.ConclusionCKD was associated with increased pTau217 concentrations when measuring pTau217 but not when using the pTau217 ratio. Additional research is needed to better understand the confounding effects of CKD in the clinical interpretation of plasma pTau217 assays.
The amyloid PET status in Primary Progressive Aphasia
Authors: Shimizu Soichiro , Yamamoto Ryo , Inagawa Shoya , Takenoshita Naoto 
Published: January 2025

AbstractBackgroundPrimary Progressive Aphasia (PPA) is a clinical and symptomatic concept due to neurodegenerative diseases which language symptom was dominant from early clinical stage. PPA is categorized into 3 subtypes such as Progressive non‐fluent aphasia (PNFA), Semantic dementia (SD), and logopenic progressive aphasia (LPA). In this study, we compared the differences of PPA subtypes depend on amyloid PET results.MethodWe recruited PPA patients who underwent standard aphasia test (SLTA) as Japanese aphasia test, cerebrospinal fluid AD biomarker, and amyloid PET. We divided into Amyloid PET positive (A(+) PPA) and negative (A(‐) PPA) group. then we compared the characterization of SLTA results and CSF biomarker between two groups.ResultA total of 15 patients were included. There were 7 patients in A (+) PPA groups (2 males and 5 females, age: 65.3±8.3 years), and 8 patients in A (‐) PPA group (6 males and 2 females, age: 66.6±11.2 years). Regarding cerebrospinal fluid AD biomarkers, a significant decrease in Aβ42/40 (p < 0.01) and significant elevation in P‐tau (p<0.01) was observed in the A (+) PPA group compared to the A (‐) PPA group. In SLTA, the A (+) PPA had LPA: 57% and transcortical sensory aphasia: 29%. on the other hand, A (‐) PPA group had PNFA: 38% and SD: 50%.ConclusionThis study showed there is the possibility of SLTA may be useful to predict AD pathology in patients with PPA.
Factors associated with loneliness among Chilean family carers of people living with dementia
Authors: Miranda‐Castillo Claudia , Tapia‐Muñoz Thamara 
Published: January 2025

AbstractBackgroundThe risk of developing loneliness in informal carers of people with dementia is high. Individual and cultural factors might play a differentiated role in the explanation of loneliness. The aim of this study was to describe loneliness levels in a group of family carers in Chile and its associated factors.MethodA sample of 283 Chilean carers was surveyed about loneliness (measured with the 3‐item of the revised UCLA scale) carer’s personality, and sociodemographic and health factors. Sociodemographic and clinical data from the person living with dementia was also reported by carers. Multiple linear regression models using bootstrap errors (1000 iterations) were carried out to determine predictors of loneliness.ResultsCarers were, on average, 59 years old, mostly women (79%), married or in a partnership (59%), with children (78%), and caring for a parent (54%) with Alzheimer’s Disease (74%). The average level of loneliness was 4.33 (range: 3‐9), and 12% of carers reported problematic loneliness (³6). Forty‐two percent of loneliness variance was explained by emotion‐focused coping, age, extraversion, neuroticism, gain, social support, and depressive and anxiety symptoms. In a final model, gain (Coef. ‐0.050; 95% CI: ‐0.085 to ‐0.015) and emotion‐focused coping were negatively associated with loneliness (Coef. ‐0.028; 95% CI: ‐0.050 to ‐0.006), whilst depressive symptoms were positive associated with loneliness (Coef. 0.089; 95% CI: 0.050 – 0.129).ConclusionsResearch usually focuses on negative aspects of caregiving. However, the perception of gain and emotion‐focused coping mechanisms used by carers can be protective factors against loneliness. Non‐pharmacological interventions might benefit from the development of those factors.
Associations Between Choroid Plexus Integrity and Cognitive Decline in Aging: Insights from Advanced MRI Analysis
Authors: Gong Zhaoyuan , Bilgel Murat , Faulkner Mary E , Bae Jonghyun , Laporte John P , Guo Alex , Resnick Susan M. , Egan Josephine M. , Bouhrara Mustapha 
Published: January 2025

AbstractBackgroundThe choroid plexus (CP), a vital component in the brain's ventricles, is crucial for cerebrospinal fluid (CSF) production and maintenance of the brain's physiological environment. It plays a key role in regulating neuroinflammatory responses, clearing harmful substances, producing neurotrophic factors and signaling molecules, and forming blood‐CSF barrier. Consequently, changes to the CP’s structural integrity could disrupt brain homeostasis and lead to cognitive impairment. Indeed, recent research has highlighted CP alterations in aging as well as in various cognitive disorders including Alzheimer's and Parkinson's diseases. This study investigates the correlation between the macrostructural and microstructural integrity of the CP and longitudinal cognitive changes in cognitively unimpaired individuals.Method116 cognitively unimpaired participants from the BLSA and GESTALT underwent advanced MRI, including relaxometry (T1 and T2) and diffusion tensor imaging (DTI), enabling the quantification of CP volume, fractional anisotropy (FA), and mean diffusivity (MD). Participants received cognitive assessments at visits preceding and concurrent with MRI scans (320 visits total) to measure memory, attention, executive function, verbal fluency, and processing speed (Table 1). Linear mixed‐effects models were used to analyze the association between MRI metrics and longitudinal cognitive changes, adjusting for age, sex, education, and race.ResultOur study found that larger CP volume, elevated T1 and T2 values, and higher MD values, all indicative of compromised macrostructural or microstructural integrity, were associated with faster declines in various cognitive domains (Table 2). Particularly, the association was found in memory, verbal fluency, and processing speed for CP volume; in attention, executive function, and processing speed for T1 and T2 (Figure 1); and in attention, executive function, and processing speed for MD. Conversely, lower FA values, representing deteriorated microstructural integrity, correlated with accelerated decline in memory, attention, verbal fluency, and processing speed.ConclusionThis study highlights a significant association between CP characteristics and cognitive decline in cognitively unimpaired individuals. These findings underscore the importance of the CP in cognitive health and emphasize the need for further research into the role of the CP in healthy aging, potentially opening new pathways for early detection and intervention in cognitive decline.
Rehabilitation participation and one‐year cognitive and affective changes in adult day service users with dementia
Authors: Tanaka Naofumi , Ouchi Yoshitaka , Wang Yin‐Jung , Kasuya Masashi 
Published: January 2025

AbstractBackgroundDay care services provide various activities, including rehabilitation, to maintain and improve physical function and social participation of older people. However, the relationship between rehabilitation participation and emotional changes in older adults with dementia who use day care services is not well understood.MethodThe participants were 157 older adults living in the community who used day‐care services. Users with MMSE scores less than 10 at the initial and one‐year evaluation were excluded. Other assessments were the Geriatric depression scale‐15 (GDS‐15), the Apathy evaluation scale (AES) and the Short physical performance battery (SPPB). Rehabilitation participation was averaged over three consecutive days of use using the Pittsburgh Rehabilitation Participation Scale (PRPS), with the group with a PRPS greater than 4 points divided into two groups: good and poor rehabilitation participation groups. MMSE, GDS, AES and SPPB scores were compared using Wilcoxon’s rank sum test at the initial and one‐year follow‐up.ResultThe age of the participants was 83 ± 7 years and 43/114 were men/women. When further divided into three groups according to MMSE score (≥24, 20‐23 and 19‐10), the good rehabilitation group with an MMSE score of 19‐10 had a significantly higher AES score (p<0.001) and a significantly lower SPPB score (p = 0.016).ConclusionAmong older adults with dementia using day care services, the group with good participation in rehabilitation was suggested to be at risk of increased apathy and reduced lower limb motor function after one year.
Identifying distinctive role of sarcopenia components for cognitive impairment with multimodal neuroimaging in non‐dementing older adults
Authors: Kim Sunghwan , Wang Sheng‐Min , Kang Dong Woo , Um Yoo Hyun , Yoon Han Min , Lee Soyoung , Choe Yeong Sim , Kim Regina EY , Kim Donghyeon , Lee Chang Uk , Lim Hyun Kook 
Published: January 2025

AbstractBackgroundAlthough previous studies have demonstrated cognitive impairment in elderly individuals with sarcopenia and its neuronal substrates, there is no comprehensive model integrating multiple brain pathologies to predict cognitive impairment associated with sarcopenia. The aim of this study was to explore a comprehensive prediction model for cognitive impairment in sarcopenia using multimodal neuroimaging methods in non‐demented older adults.MethodThis cross‐sectional study used data from the Catholic Aging Brain Imaging Database study, a population‐based cohort study with magnetic resonance imaging (MRI) scans, positron emission tomography (PET) scans, and clinical data. A total of 528 non‐demented older adults, with or without sarcopenia, was included. We measured three key components of sarcopenia: skeletal muscle index (SMI), hand grip strength (HGS), and the five‐times sit‐to‐stand test (5STS).ResultSarcopenia measures related to muscle mass, power and speed demonstrated significant partial correlations with cognitive function. Cortical thickness was significantly associated with muscle power (HGS; left superior temporal cortex) and speed (5STS; bilateral precentral and insula cortex), while amyloid‐beta (Aß) hand distinctive association with muscle mass (SMI). In the path model, brain atrophy was primarily influenced by SMI and HGS through Aβ retention and periventricular white matter hyperintensity (pvWMH), respectively, resulting in cognitive impairment. On the other hand, the 5STS directly affected brain atrophy, contributing to cognitive decline.ConclusionSarcopenia sub‐domains, including muscle mass, power, and speed, showed distinctive associations with cognitive impairments related to Aß burden, pvWMH, and brain atrophy. Therefore, treatments targeting each sub‐domain should be considered to prevent cognitive decline associated with sarcopenia.