bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of subcortical grey matter structures in neuropsychiatric symptoms from cognitively healthy tot mild cognitive impairment: a population‐based study
Authors: vom Hofe Ilse , Luik Annemarie I. , Vernooij Meike W. , Ikram M. Arfan , Wolters Frank J. 
Published: January 2025

AbstractBackgroundNeuropsychiatric symptoms are common in the prodromal phase of dementia, and may be related to altered structure and function of subcortical grey matter involved in emotion regulation. We aimed to determine the association between subcortical grey matter volume and occurrence of neuropsychiatric symptoms in a population‐based study.MethodBetween 2009‐2015 dementia‐free participants from the population‐based Rotterdam Study underwent 1.5T brain MRI. Volumes of the accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus were determined using FreeSurfer 6.1. Symptoms of depression and anxiety were assessed using the Center for Epidemiologic Studies Depression (CES‐D) scale and the anxiety subscale of the Hospital Anxiety and Depression scale (HADS‐A). We determined cross‐sectional associations between subcortical volumes (per 1 standard deviation [SD] decrease) and continuous CES‐D and HADS‐A scores using linear regression, and with clinically significant symptoms (CES‐D≥16;HADS‐A≥8) using logistic regression. Models were adjusted for demographics, lifestyle factors, comorbidities and co‐medication use. We repeated analyses stratifying on cognitive status (healthy/subjective complaints/MCI).ResultOf 3452 participants (mean age 69.3 years, 55.2% women), 284 (8.2%) scored positive for clinical depressive symptoms, and 270 (7.8%) for clinical anxiety symptoms. Smaller hippocampal volume was associated with higher odds of clinical depressive symptoms (odds ratio [95%CI]: 1.27[1.05‐1.52], p = 0.01). In contrast, smaller volumes of the caudate were associated with less depressive symptoms (mean difference in log‐transformed score [95%CI] for caudate: ‐0.06[‐0.10;‐0.02], p<0.01, and pallidum: ‐0.04[‐0.08;0.00], p = 0.05). Smaller volumes of the caudate and pallidum were also associated with less anxiety (caudate: ‐0.04[‐0.07;‐0.01], p<0.01, pallidum: ‐0.05[‐0.09;‐0.02], p<0.01), accompanied for the caudate by a lower odds of clinical anxiety symptoms (OR[95%CI]: 0.84[0.72;0.98], p = 0.03). No associations were observed with the accumbens, amygdala, putamen, or thalamus. Associations were observed in cognitively healthy participants, as well as in those with subjective cognitive complaints or MCI.ConclusionIn community‐dwelling older adults, volumes of the hippocampus, caudate, and pallidum are associated with neuropsychiatric symptoms, which do not differ by neurodegenerative disease stage. These findings support a complex role of subcortical volumes in the occurrence of neuropsychiatric symptoms in the older population.
Association of plasma glial fibrillary acidic protein (GFAP) and Mediterranean diet
Authors: Bandara E.M.S. , Gardener Samantha L , Pedrini Steve , Hone Eugene , Smith Stephanie Rainey , Martins Ralph N , Fernando Warnakulasuriya Mary Ann Dipika Binosha 
Published: January 2025

AbstractBackgroundEvidence suggests that diet may play a modifiable role in reducing Alzheimer’s disease (AD) risk. Higher adherence to the Mediterranean diet (MeDi) is linked to a lower incidence of mild cognitive impairment (MCI) and AD. Increasing evidence indicates the potential utility of a cytoskeletal protein found in astrocytes, plasma Glial Fibrillary Acidic Protein (GFAP), as a marker specific for AD pathogenesis. However, the relationship between plasma GFAP level and the MeDi has not been fully determined. This cross‐sectional study examined whether MeDi diet as a whole or the individual components, were associated with plasma GFAP levels in an Australian older adult cohort drawn from the larger Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing.MethodsCognitively unimpaired participants (n = 116) and individuals with MCI (n = 47) (mean age 75.37 ± 6.31; 44% male) completed a self‐reported food frequency questionnaire and had plasma GFAP levels measured using SIMOA platform. A score for the MeDi was generated for each individual. Linear regression models evaluated the association between plasma GFAP and the MeDi score, as well as individual MeDi components, including sex and age as covariates.ResultsMeDi score was not associated with plasma GFAP level. However, for individual MeDi components, dairy intake was positively associated with GFAP level (β = 0.107±0.039, p = 0.007).ConclusionsThis study is one of the first to report an association of plasma GFAP level with dietary components in an older adult cohort. The results suggest that dairy intake influences astrocyte reactivity. Further studies will include evaluation of plasma GFAP levels with additional dietary patterns, and individual dietary components to fully investigate the modifiable effect of diet on AD process.
Cerebrospinal fluid glial fibrillary acidic protein provides differential diagnostic value in some forms of dementias
Authors: Eriksson Pontus , Skillback Tobias , Kern Silke , Jönsson Linus , Blennow Kaj , Eriksdotter Maria , Zetterberg Henrik 
Published: January 2025

AbstractBackgroundGlial fibrillary acidic protein (GFAP) is a marker of cerebral astrogliosis and occasionally elevated in patients with dementia. GFAP in cerebrospinal fluid (CSF), is routinely requested in referrals to neurochemistry laboratories; however, its ability to differentiate dementias and diagnostic capability is unclear. Our aim was to elucidate this, using two large datasets.MethodFirst, GFAP data measured since 2015 was retrieved from the database of the Clinical Neurochemistry Laboratory at the Sahlgrenska University hospital. We then cross‐referenced with the Swedish dementia registry (SveDem). Here, information on ten different diagnoses such as early onset AD (EAD [<65 years]), late onset AD (LAD [≥65 years]), Parkinson disease with dementia (PDD), vascular dementia (VaD) and frontotemporal dementia (FTD), each with specific diagnostic criteria, were retrieved.The GFAP data was log10‐transformed, followed by an analysis of covariance (ANCOVA) and a subsequent post‐hoc Tukey’s test, with GFAP as dependent variable, diagnosis as independent variable and sex and age as covariates.ResultIn total, 1912 individuals (mean [SD] age, 71.9 [8.2] years; 52% male), were included. Lower log10‐transformed GFAP concentrations were seen in PDD (mean [SD], 2.68, [0.28] pg/mL), than in EAD, LAD, VaD and FTD; here, mean concentrations of 2.76 (0.24), 2.89 (0.23), 2.89 (0.32) and 2.76 (0.25) pg/mL were observed, respectively.In the post hoc analysis, GFAP differentiated VaD from EAD (p<0.001). PDD concentrations were significantly different from VaD (p<0.001) and LAD (p<0.001). Further, it also differentiated FTD from VaD (p=0.006) and LAD (p=0.001).ConclusionCSF GFAP could on a group level help differentiate VaD from EAD, FTD and PDD. Also, it could differentiate PDD from LAD. These results bear potential clinical relevance, where clinicians in some uncertain cases could use this marker as a differential tool.
The Effects of Single Instance Transcutaneous Vagus Nerve Stimulation on Cognition in MCI: A Randomized, Double‐Blind, Placebo‐Controlled Crossover Trial
Authors: Ho Brian D. , Velez Xavier A. , Waters Abigail B. , O'Neal Alexandria G. , Lamb Damon G. , DeKosky Steven T. , Porges Eric S. , Cohen Ronald A. , Williamson John B. 
Published: January 2025

AbstractBackgroundTranscutaneous stimulation of the auricular branch of the vagus nerve (tVNS) was administered to participants diagnosed with mild cognitive impairment (MCI) to improve word‐list memory (primary outcome) and other cognitive skills.MethodA randomized, double‐blind, placebo‐controlled crossover design was used for this trial. Participants with MCI (n = 59) were sorted into one of two sequences: Sham‐tVNS or tVNS‐Sham. In the Sham condition, electrodes were placed on opposite sides of participants’ left earlobes; the return electrode was placed on the mesial face of the earlobe. In the tVNS condition, electrodes were placed over the left auricular branch of the vagus nerve with the return electrode placed anterior to the tragus and one placed on the posterior face of the tragus to the interface of the auditory canal. In both conditions, stimulation parameters were set to 20Hz, 100 µs pulse width of alternating polarity, and intensity ramped from 0 to the threshold of discomfort and then reduced by 20%. During stimulation, participants simultaneously underwent comprehensive neuropsychological testing to assess various cognitive abilities. Test batteries were identical at both study visits, which were separated by at least 72 hours to avoid carryover effects, except where alternative forms were available. Structural brain MRI was also acquired.ResultPerformance on the immediate and delayed recall trials of the Rey Auditory Verbal Learning Test (RAVLT) did not significantly differ by treatment condition (p = 0.072 and p = 0.279, respectively). Likewise, performance on other cognitive tests did not significantly differ between treatment conditions (p = 0.101 to 0.958).ConclusionA single bout of tVNS does not appear effective for improving cognition in individuals with MCI.
Sex/Gender Differences in the Pattern of Comorbid Depressive Symptoms, Pain, and Sleep Problems among Older Mexican Americans With and Without Probable Dementia
Authors: Milani Sadaf Arefi , Brigham Trinity , Fang Kuo Yong‐ , Downer Brian , Markides Kyriakos S. , Raji Mukaila A 
Published: January 2025

AbstractBackgroundDepression, pain, and sleep problems commonly co‐occur (overlap) among older adults. Data are lacking on the extent, pattern and sex/gender differences of overlap of these symptoms in adults aged ≥80 and living with dementia. Our objective was to examine patterns and sex/gender differences in overlapping depression‐pain‐sleep symptoms among older Mexican Americans with and without probable dementia.MethodWe used data from Wave 7 (2010/2011) of the Hispanic Established Population for the Epidemiologic Study of the Elderly, a study of Mexican Americans aged ≥75, residing in the Southwestern US. Participants were considered to have probable dementia if they scored <21 on the Mini‐Mental State Examination and had ≥1 activity of daily living limitation. Pain was defined as pain on weight‐bearing. Depressive symptoms were defined as having scores of 16 or more on the Center for Epidemiologic Studies Depression Scale. Clinically relevant sleep problems were defined as having trouble falling asleep, waking up several times per night, trouble staying asleep, or waking up feeling tired for at least 15 days in the past month. We used descriptive statistics to describe the prevalence and overlap in these three symptoms, by dementia status and sex/gender.ResultOur sample was 85.7 years old on average and 65% were women (n = 974). Almost one‐third of participants (32.4%) had dementia. About 16% of participants with probable dementia reported overlapping depression‐pain‐sleep symptoms, compared to 5.5% of those without dementia (Figure 1). When stratified by cognitive status and sex/gender, 14.3% of men and 17.0% of women with probable dementia reported all three symptoms, compared to 2.0% of men and 7.6% of women without dementia.ConclusionParticipants with probable dementia reported three times the frequency of co‐occurrence of clinically relevant depressive symptoms, pain, and sleep problems compared to those without dementia. Women, regardless of cognitive status, more frequently reported depression‐pain‐sleep symptom overlap, compared to men, but the gender disparity was smaller for those with probable dementia. The presence of one symptom should alert clinicians to screen for, treat, and manage the other two. Evidence supports common underlying mechanisms for these three highly co‐occurring conditions, potentially informing therapeutic decision‐making in patients with dementia.
Phase 1 Single and Multiple Dose Clinical Trials (ASCENT‐1 and ASCENT‐2) for Dose‐Finding of PRX012 in Participants with Biologically Confirmed Alzheimer’s Disease
Authors: Swanson Chad , Martényi Ferenc , Tooker Ryan E. , Campbell Brian M. , Johnson Ann , Li Lingnan , Quiceno Mary E. , Zago Wagner M. , Kinney Gene G. , Garren Hideki 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by the presence of brain amyloid beta (Aβ) plaques and stages of memory loss, cognitive decline, psychological and psychiatric changes, inability to perform activities of daily living, dementia, and eventually death. Recent evidence demonstrates the slowing of clinical decline with plaque‐clearing, anti‐Aβ monoclonal antibodies. PRX012 is a humanized monoclonal antibody that targets and clears known pathogenic forms of Aβ in development for subcutaneous (SC) use. Ongoing phase 1 clinical trials are evaluating the optimal dose of PRX012 in participants with AD.MethodPRX012‐101 (ASCENT‐1) is a phase 1, randomized, double‐blind, placebo‐controlled, single ascending dose clinical trial to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics of PRX012 in healthy volunteers and participants with biologically confirmed AD (via amyloid PET). Subjects are given a single SC injection of PRX012, from 70 mg up to 400 mg, or placebo and followed for 85 days.PRX012‐102 (ASCENT‐2) is a phase 1, randomized, double‐blind, sponsor‐open, placebo‐controlled, multiple dose clinical trial to evaluate the safety, tolerability, immunogenicity, pharmacokinetics, and pharmacodynamics of PRX012 in participants with biologically confirmed AD. Participants are assigned to one of two groups based on APOE genotype: Group A subjects with AD who are heterozygous‐ or non‐carriers of APOE4 alleles, and Group B subjects with AD who are homozygous for APOE4. Cohorts of APOE4 homozygous subjects were incorporated to allow for better representation and more complete characterization of the profile of PRX012 in homozygous carriers, as these individuals make up a small proportion of typical Alzheimer’s study populations. Subjects are given a series of 6 monthly SC injections of PRX012, from 45 mg up to 400 mg, or placebo.ResultData from both ASCENT‐1 and ASCENT‐2 will support dose‐finding for PRX012 through generation of a robust dataset.ConclusionPhase 1 development of PRX012 will support future late‐stage clinical trials that have the potential to position PRX012 as a best‐in‐class, next‐generation once‐monthly subcutaneous antibody for the treatment of AD.
Principal Factors Contributing to Cognitive Impairment in Homebound and Bedridden Frail Elderly Individuals from Low‐Resource Communities in Brazil
Authors: REAL ANA PAULA BERNARDES , MORAES FLAVIA LANNA DE , MORAES EDGAR NUNES DE , MACHADO CARLA JORGE 
Published: January 2025

AbstractBackgroundCognitive impairment (CI) is a major geriatric syndrome, leading to the loss of an individual’s decision‐making autonomy and representing a significant caregiving burden for families. It is commonly encountered in clinical practice and can be caused by dementia (major neurocognitive disorder), depression, delirium, or mental illness.MethodsTo assess the prevalence and primary causes of cognitive impairment (CI), as well as its correlation with other clinical conditions among bed‐bound or home‐bound elderly individuals from low‐resource communities in Brazil, we carried out a cross‐sectional study. This study involved patients from a public health system’s home care service, who received care from specialized geriatric‐gerontological teams in the low‐income communities of Belo Horizonte/MG, from 2011 to 2022. Statistical analyses were performed using Stata/SE for Macintosh 12.0.ResultsThe study evaluated 1,391 elderly individuals, of which 67.8% were female, with an average age of 81.0 years (range 60 – 105). The prevalence of CI was 73.5%. The following probable etiologies were observed: dementia (82%), depression (40%), delirium (8.3%), and “mental illness” (15%), which were not mutually exclusive. The likelihood of CI among patients with delirium and mental illness was, respectively, 4.9 times (OR = 4.9; 95% CI 1.9‐12.8; p<0.001) and 7.6 times (OR = 7.6; 95% CI 4.1‐14.1; p<0.001) the likelihood of CI among patients without these conditions, indicating a significant and positive association. Age 80 years or older (OR = 1.6; 95% CI 1.2‐2.1; p = 0.003) and the presence of a high degree of frailty (OR = 2.2; 95% CI 2‐2.4) were also positively associated with CI. Polypharmacy was negatively associated with cognitive impairment (OR = 0.61; 95% CI 0.45; 0.82; p = 0.001).ConclusionsThe prevalence of CI was quite high in the population evaluated, present in nearly three‐quarters of the elderly. Dementia was the primary cause, followed by depression, mental illness and delirium. The association between dementia and depression was significant, complicating differential diagnosis while delirium constitutes the least frequent cause of CI in community‐dwelling elderly individuals.
Demographic, clinical and Alzheimer’s disease risk characteristics associated with interest in APOE disclosure amongst middle‐aged Australian adults
Authors: Rosenich Emily , Olver Hannah , Perin Stephanie , Haeusler Ruby , Foreman Tamar , Karlawish Jason , Lim Yen Ying 
Published: January 2025

AbstractBackgroundClinical guidelines in Australia discourage disclosure of apolipoprotein E (APOE) genotypes but advances in Alzheimer’s disease (AD) therapeutics will likely change this. Limited work has assessed interest in APOE disclosure in Australian adults, and it remains unclear which characteristics are associated with interest within this sample. In a large group of middle‐aged adults, this study aimed to describe interest in APOE disclosure and investigate differences in demographic and clinical characteristics and AD risk perceptions among groups with varying interest in disclosure.MethodCognitively unimpaired middle‐aged adults aged 40‐70 (N = 460) enrolled in the Healthy Brain Project or BetterBrains Trial completed the Knowledge, Interest and Preferences for APOE Testing and Disclosure questionnaire. Online assessments measured demographics (age, sex, education, ethnicity, dementia family history), anxiety and depressive symptoms, subjective cognition, perceived risk of developing AD, and knowledge of AD. Participants were categorized into groups based on self‐reported interest in disclosure (interested/want more information/not interested). Frequencies described interest in APOE disclosure and perceived benefits and concerns. Kruskal‐Wallis and chi‐square tests assessed whether demographic and clinical characteristics and AD risk perceptions differed between groups.ResultOnly 6% of participants were not interested, with most either interested (51%) or wanting more information about APOE (43%). Compared to participants who were not interested, interested participants were younger, more knowledgeable about AD, more likely to report any family history of dementia, had stronger beliefs in negative aging stereotypes and about the benefits of engaging in protective health behaviors to modify AD risk, had greater hope for an AD cure, and greater perceived risk of AD‐related mortality (Table 1). Amongst interested participants, motivation to change behaviors to reduce AD risk was the most common perceived benefit of disclosure (82%), whereas worry about attributing subtle memory changes to impending AD dementia was the most common concern (23%).ConclusionMost middle‐aged Australian adults sampled expressed an interest in APOE disclosure in a research setting. Contrary to previous findings, greater subjective cognitive concerns did not influence interest. Instead, results highlight that an array of biopsychosocial factors influence interest in APOE disclosure. Findings will inform the development of disclosure protocols for Australian populations.
Association of Multimorbidity and Plasma Biomarkers of Alzheimer’s Disease: The HABS‐HD Study
Authors: Jiang Xiaqing , O'Bryant Sid E. , Rissman Robert A , Johnson Leigh A. , Peltz Carrie B. , Yaffe Kristine 
Published: January 2025

AbstractBackgroundMultimorbidity, known as the coexistence of two or more chronic conditions in the same individual, is prevalent among older adults and has been linked to an increased risk of dementia. Yet, little is known about its relationship with plasma Alzheimer’s disease (AD) biomarkers, especially in diverse populations. In the Health and Aging Brain Study: Health Disparities (HABS‐HD), we investigated the association of multimorbidity burden and plasma AD biomarkers.MethodWe cross‐sectionally studied a diverse cohort of 2,110 dementia‐free participants (63% women, 43% Mexican Americans [MA], 44% non‐Hispanic Whites [NHW], and 13% Blacks) aged ≥50 years (mean age 65.6±8.5) at baseline (2017‐2023). Plasma AD biomarkers, including β‐amyloid (Aβ)42/40, total and phosphorylated tau (t‐tau and p‐tau181), and neurofilament light (NfL), were assayed using ultra‐sensitive Simoa. Multimorbidity burden was measured by the total number of 16 chronic conditions, defined based on laboratory values, medical history, objective measures, and self‐report. We conducted linear regression to assess the associations of multimorbidity burden with plasma AD biomarkers and effect modification by race/ethnicity.ResultMedian multimorbidity burden was 3 (interquartile range 2‐4), with 86% of the participants having ≥2 chronic conditions: 14% with 0‐1, 41% with 2‐3, and 45% with ≥4 chronic conditions. After adjusting for age, sex, and race/ethnicity, multimorbidity burden was significantly associated with a lower level of Aβ42/40 and higher levels of t‐tau, p‐tau181, and NfL (Table 1). The associations remained significant after further adjustment for education, physical activity, and serum creatinine, except for Aβ42/40, in which the association was attenuated. We found significant interactions by race/ethnicity (p<0.05, Figure 1), with the associations of multimorbidity with p‐tau181 and NfL being stronger among MAs and Blacks than among NHWs.ConclusionGreater multimorbidity burden is associated with elevated p‐tau and NfL, particularly among race/ethnic minorities. This suggests that multimorbidity may be involved in tau‐related and neurodegenerative pathways of AD, as well as other peripheral clearance mechanisms. Efforts to interpret plasma biomarkers for screening purposes could benefit from considering multimorbidity and potentially tailored approaches in diverse populations.