bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of prior alcohol misuse with cognitive impairment and Alzheimer’s disease
Authors: Housini Mohammad , Zhou Zhengyang , O'Bryant Sid E. , Phillips Nicole , Barber Robert , Polimanti Renato A , Pathak Gita 
Published: January 2025

AbstractBackgroundAlcohol use is hypothesized to be a risk factor for cognitive impairment (CI) and Alzheimer’s disease (AD). However, its role is often complex in diagnosing and distinguishing alcoholic dementia from AD. Hence, several AD‐focused studies exclude participants with possible alcohol misuse history, creating major challenges to investigate this connection. Given that alcohol use is a prevalent yet modifiable factor, it is crucial to study their connection to provide key insights.MethodWe investigated the association of alcohol misuse history with CI and AD in three major AD studies: Health and Aging Brain Study‐Health Disparities (HABS‐HD, N = 3,035), Texas Alzheimer’s Research Care Consortia (TARCC, N = 14,655), and Alzheimer’s Disease Neuroimaging Initiative (ADNI, N = 2,430). Each study collected different metrics of prior alcohol misuse. In HABS‐HD, we used total Alcohol Use Disorder Identification Test (AUDIT) score to define alcohol misuse, while prior alcohol misuse was collected as part of medical history in TARCC and ADNI cohorts. CI was defined as presence of any type of mild cognitive impairment, and AD was defined by each of the respective cohort. We performed the association using regression and two covariate models: Model 1: age, sex, and self‐reported race‐ethnicity; Model 2: Model1+education. To improve statistical power, we performed a meta‐analysis of the three cohorts using fixed‐effects and random‐effects model.ResultWe meta‐analyzed the results from the three for a total sample size of 19,331; 5,345 individuals with AD, 4,820 individuals with CI, and 603 individuals with prior alcohol misuse. We found an association of prior alcohol use with AD (Model 1: OR = 1.87; 95CI = 1.55‐2.26; p‐value = 7.99×10−11; Model 2: OR = 1.75; 95CI = 1.33‐2.29; p‐value = 5.0×10−5), and CI (Model 1: OR = 1.47; 95CI = 1.21‐1.77; p‐value = 6.23×10−05; Model 2: OR = 1.39; 95CI = 1.06‐1.84; p‐value = 1.75×10−02). There was no heterogeneity among the cohort‐specific effects contributing to the meta‐analysis. (heterogeneity p‐value> 0.05).ConclusionLeveraging multiple AD cohorts, we show that prior alcohol misuse is associated with CI and AD, warranting further inquiry into possible molecular and biological processes that intersect between AD and alcohol abuse/dependence.
The Impact of Physical Exercise on Hippocampal Atrophy in Mild Cognitive Impairment and Alzheimer’s Disease: A Meta‐analysis in Support of Early Detection and Intervention
Authors: Kress Gavin T , Popa Emily S. , Merrill David A. , Bramen Jennifer E. , Siddarth Prabha 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) presents a significant global health challenge, with limited pharmacological interventions available. Physical activity (PA) is a promising therapeutic approach for delaying AD onset and mitigating neuropathology. Only a handful of meta‐analyses have explored the effects of exercise interventions on structural MRI (sMRI)‐estimated brain volumes in adults with mixed cognitive statuses, two of which found positive effects on left and bilateral hippocampal volume (HV). No meta‐analysis to date has solely included studies examining the effect of PA on sMRI outcomes in individuals with cognitive impairment (CI). In this meta‐analysis, we examined whether there is evidence to support the hypothesis that PA interventions positively impact HV in individuals with CI. We also assessed whether the level of CI (Mild Cognitive Impairment (MCI) vs. AD) impacted this relationship.MethodWe identified six controlled trials that investigated effects of PA interventions on HV in older individuals with cognitive impairment and met inclusion criteria (Table 1). These included 236 participants with AD, MCI, or preclinical AD. Data were extracted and analyzed following Cochrane guidelines (Figure 1). We used a random‐effects model (PythonMeta library: Python 3.9) to estimate the mean change in HV pre‐ and post‐exercise intervention. Forest plots, Hedges’ g funnel plots, and Egger’s test were used to assess unbiasedness and visualize intervention effects, and Tau2, Cochran’s Q, and I2 were calculated to assess heterogeneity.ResultThe primary analysis revealed a significant positive effect of exercise on total hippocampal volume (p = .04). However, sub‐group analyses indicated a significant preservation of HV only in individuals with MCI (Table 2; Bilateral: p = 0.05; L: p = 0.003; R: p<0.001), but not in those with AD (Bilateral: p = 0.2; L: p = 0.5; R: p = 0.8). Egger’s test indicated no evidence of publication bias (p = 0.3). Subgroup analyses also revealed significant heterogeneity only within the MCI cohort for the total and left HV.ConclusionExercise interventions demonstrated a moderate, significant effect in preserving HV among individuals with MCI, but not AD, highlighting a potential therapeutic benefit, particularly in earlier disease stages. These findings encourage future investigation of PA as a treatment for MCI and further incentivize earlier detection.
Sleep and Neurocognitive Performance in Middle‐Aged Latina Women in an Agricultural Community: Insights from the CHAMACOS Maternal Cognition Study
Authors: Rojas Nadia , Calderon Lucia , Kogut Katherine , Rodriguez Maria Teresa , Romero Monica , Garcia Lizari , Rodriguez Hector , Guadamuz Jenny , Eskenazi Brenda , González Hector M , Torres Jacqueline M 
Published: January 2025

AbstractBackgroundLatino adults face a 1.5‐to‐2‐fold increased risk of ADRDs compared to non‐Hispanic whites. Sleep disturbances among Latinos have been linked with worse neurocognitive function and a higher risk for ADRD. Limited research exists on sleep and neurocognitive function among middle‐aged Latinas. This study addresses these gaps by exploring the relationship between sleep duration, quality, nap frequency, and cognitive function in Latinas living in an agricultural community in California.MethodData come from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Maternal Cognition study, which included 513 middle‐aged Latina women (mean age: 48.8) living in an underserved agricultural community in California. Average nightly sleep duration, sleep quality, and nap frequency were measured via self‐report. Participants completed the SOL‐INCA Neurocognitive Assessment, which yielded global and domain‐specific cognitive z‐scores (memory, executive function, verbal fluency). We separately estimated associations between each sleep measure and cognitive scores, controlling for socio‐demographic and health‐related covariates. In models of continuous hours of nightly sleep, we considered non‐linear associations.ResultParticipants reported a mean of 8.6 hours of nightly sleep; nap frequency was 64.8% no naps, 22.2% 1‐2 naps, 7.2% 3‐4 naps, and 5.9% 5+ naps. Sleep quality was 48.5% very sound or sound, 30.10% average, and 21.36% restless or very restless. We observed an inverted U‐shaped association between sleep duration and memory, executive function, and global cognitive z‐scores. Taking 1 or 2 naps per week (vs. zero naps) was associated with higher memory z‐scores (Coef: 0.21, 95% CI: 0.02, 0.39), while napping 5 or more times per week was associated with lower memory z‐scores (Coef: ‐0.61, 95% CI: ‐0.94, ‐0.29) and global cognitive function z‐scores (Coef: ‐0.25, 95% CI: ‐0.46, ‐0.04). We did not observe associations between self‐reported sleep quality and neurocognitive scores.ConclusionOur findings emphasize the significant connection between multiple measures of sleep duration, quality, and neurocognitive function. The results from this study can provide valuable insights for developing interventions targeted at improving sleep among Latinas living in rural settings. Interventions that target improved sleep may benefit neurocognitive function among middle‐aged Latinas living in agricultural settings.
Midlife physical activity and amnestic MCI: Impact on hippocampal volume
Authors: Tippett Lynette J , Merrick Jenna , Roberts Reece P , Morgan Catherine A , Melzer Tracy R , Kirk Ian J , Cawston Erin E , Williams Joanna M , Buchanan Sarah M , Cutfield Nicholas J , Dalrymple‐Alford John C , Anderson Tim J ,   The New Zealand‐Dementia Prevention Research Clinics, New Zealand
Published: January 2025

AbstractBackgroundThe projected doubling of dementia prevalence by 2050 highlights the critical importance of altering the dementia trajectory and associated burden. Modifiable risk factors account for 40% of dementia risk (Livingston et al, 2020), including physical inactivity in late life. Protective effects of physical activity (PA) may be greater during earlier stages of neuropathological change, either directly by influencing the brain, or, indirectly by protecting against hypertension, obesity, and diabetes. We investigated whether midlife PA (i) differs in participants spanning the continuum from healthy older adults to clinically diagnosed early AD, and (ii) is related to hippocampal volume later in life.Method214 individuals from the New Zealand‐Dementia Prevention Research Clinics participated (31 healthy controls; 56 subjective cognitive decline; 107 amnestic mild cognitive impairment (aMCI) and 20 early AD dementia). Midlife physical activity was based on the Lifetime of Experiences Questionnaire, used to derive cumulative PA frequency scores, and weighted PA frequency‐by‐intensity composite scores. Hippocampal volume was computed from 3T MRI T1‐weighted images using SPM CAT12. ANCOVAs assessed between‐group differences on transformed PA variables. Groups were reduced to cognitively unimpaired (n = 87) and aMCI (n = 107) for multiple linear regressions that assessed whether midlife PA composite and frequency scores were associated with total hippocampal volume and whether these were moderated by gender and APOE status. Age, total intracranial volume and group were entered as predictors.ResultThere were no significant between‐group differences in transformed frequency or composite midlife PA measures (p‐values > .35). Midlife composite PA and frequency PA scores were associated with hippocampal volume, with associations moderated by gender (Beta gender X PA p‐values = .02 and .03), but not APOE status. Females showed the predicted positive association between midlife exercise and hippocampal volume, but males showed negative associations. Multiple regressions with only amnestic MCI participants revealed the same patterns of associations.ConclusionThese findings suggest that the effects of midlife PA on hippocampal volume are detectable later in life in aMCI. Negative associations for males may relate to previous findings (human and animal) suggesting that leisure‐time PA is protective for the brain, but not occupational or “involuntary” exercise.
The Influence of Exercise on the Well‐being of Dementia Patients’ Caregivers
Authors: Sewerbidges‐Williams Linda B 
Published: January 2025

AbstractBackgroundThe demands of caregiving can exact a toll on unpaid caregivers’ physical and emotional well‐being. Caregivers of individuals with dementia frequently experience high levels of stress, anxiety, and depression. Physical activity is a promising intervention for promoting the well‐being of dementia caregivers. Little is known about the association between one’s level of physical activity and the well‐being of unpaid dementia patients’ caregivers. The aim of the study was to investigate the association between physical activity and well‐being of unpaid caregivers of dementia patients.MethodsThis cross‐sectional study included unpaid caregivers of dementia patients in Riverside, San Bernardino, Inyo, and Mono Counties, California. Utilizing a 31‐item questionnaire that included the International Physical Activity Questionnaire Short Form (IPAQ‐SF) and the Caregiver Self‐Assessment Questionnaire (CSAQ), participants provided insights into their physical activity levels and well‐being from July to October 2023. Logistic regression models were employed to analyze the relationship between physical activity (sedentary behavior, moderate physical activity, vigorous physical activity) and caregiver well‐being while controlling for demographic and health factors.ResultsThe survey included 152 mostly female (82.8%) and married (72.8%) respondents, with an average age of 56 years (SD = 8.4 years). The majority were aged 60 or older (65.6%) and had been caregivers for 3.5 years on average. More vigorous physical activity was associated with better well‐being (p < 0.05), but sedentary lifestyle and walking frequency was not. Gender and level of education influenced the association between physical activity and well‐being. Another notable aspect is that 85% of caregivers exhibited low well‐being.ConclusionsThis study found an association between caregiver well‐being and vigorous physical activity but no association with sedentariness and frequency of walking. Designing personalized physical activity interventions maybe focusing on vigorous exercise can enhance the well‐being of dementia caregivers, thereby alleviating the burdens associated with dementia caregiving. Future research endeavors using longitudinal designs should be conducted to delve deeper into the underlying mechanisms driving these associations.
Cholinergic white matter pathways in Alzheimer’s disease, dementia with Lewy bodies, and other neurodegenerative diseases: a post‐mortem MRI study
Authors: López‐González Francisco J. , Nemy Milan , Rabano Alberto , Grothe Michel J. , Sanchez‐Juan Pascual , Ferreira Daniel 
Published: January 2025

AbstractBackgroundIn‐vivo magnetic resonance imaging (MRI) has recently shown that patients with clinically diagnosed Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) exhibit degeneration of the cholinergic nucleus basalis of Meynert and its white matter (WM) projections through the cingulum and external capsule pathways1. Here, we propose an imaging‐pathologic validation study aimed at investigating cholinergic WM pathways using post‐mortem MRI of autopsy‐confirmed AD, Lewy body dementia (LBD), and other neurodegenerative diseases (OTH).MethodWe included 53 brain donors (34 AD, 10 LBD, and 9 OTH, mainly including frontotemporal lobe degeneration and vascular disease, Table1). All donors underwent post‐mortem MRI in situ within 5 hours after death and were later subjected to neuropathological examination performed according to published consensus criteria. Post‐mortem MRI examination included 3D T1 structural imaging and diffusion‐weighted imaging acquired using a 3T scanner. Previously established masks of cholinergic WM pathways (i.e., cingulum and external capsule pathways) were transformed from standard MNI space to each individual’s b0 image in native space using the nonlinear SyN registration algorithm. Native space mean diffusivity (MD) maps were estimated for each donor using the FMRIB Diffusion Toolbox from FSL. Microstructural properties of each participant’s cholinergic WM pathway were then estimated by averaging the MD values within the back‐transformed masks in native space. Differences in age‐adjusted MD values between diagnostic groups were analysed using the Mann‐Whitney U‐test.ResultAD donors were older than LBD donors (p = 0.007), and both groups were older than the OTH group. After adjusting for age, AD showed significantly higher MD values in cholinergic WM pathways when compared with OTH (Cohen’s d = 1.45, p<0.001) and LBD (Cohen’s d = 0.91, p<0.01) (Figure1). Elevated MD values in LBD compared to OTH did not reach statistical significance in this small sample (Cohen’s d = 0.85, p = 0.11).ConclusionWe expanded previous in‐vivo MRI findings to post‐mortem MRI and confirmed the degeneration of cholinergic WM pathways in AD. Additionally, we highlighted the difference between AD and LBD donors, with a more severe cholinergic pathway degeneration in AD donors. References 1Schumacher J, et al. Cholinergic WM pathways in dementia with Lewy bodies and AD. Brain. 2022 Jun 3;145(5):1773‐1784.
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.
Performance of the Amsterdam IADL scale in Assessing Functional Decline among Older People in Primary Health Care
Authors: Fawad Ayesha , Nilsson Maria H , Sikkes Sietske A.M. , Postema Merel C. , Stomrud Erik , Tideman Pontus , Hansson Oskar , Palmqvist Sebastian 
Published: January 2025

AbstractBackgroundThe Amsterdam Instrumental ADL Questionnaire (A‐IADL‐Q) has shown promising performance in detecting subtle impairment in IADL independency. Importantly, it has not been validated in older people in a primary care setting, i.e., where the initial work‐up and triaging of cognitive impairment occurs. The main aim was to examine the accuracy of the A‐IADL‐Q for estimating the cognitive stage in a primary care sample, both in the whole population and within the Alzheimer’s disease (AD) continuum. Secondary aims were to examine associations with the clinical dementia rating (CDR) scale and global cognition (MMSE), including the effects of non‐cognitive co‐morbidities and medications.MethodThis cross‐sectional study includes informants of 362 participants from the BioFINDER‐Primary care study. They completed the A‐IADL‐Q (higher scores = “better”) either on an iPad or at home on a computer. Cognitive stage was assessed by a dementia expert (blinded to A‐IADL‐Q scores). Amyloid status was determined using FDA‐approved CSF or PET measures. The main outcome was cognitive stage according to the NIA‐AA scale. Secondary outcomes were CDR‐sum of the boxes (CDR‐SOB) and MMSE. Receiver Operating Curves (ROC) analyses were used to calculate the area under the curves (AUCs).ResultThe mean age of participants (44.9% female) was 76.1 (SD 7.2) years. Out of which, 83 (23%) had subjective cognitive decline (SCD), 169 (47%) mild cognitive impairment (MCI), and 110 (30%) dementia. The AUC (95% CI) for differentiating between SCD versus MCI/dementia was 0.89 (0.85‐0.92), and it was 0.89 (0.85‐0.93) for SCD/MCI versus dementia. In amyloid positive participants (n = 303), AUCs were similar. Better A‐IADL‐Q scores were associated with worse results on CDR‐SOB (r = ‐0.73, p<0.001) and better global cognition (MMSE, r = 0.361, p<0.001). The effects of different co‐morbidities on the A‐IADL score, adjusted for cognitive stage, will be presented at AAIC.ConclusionOur findings suggest that the A‐IADL‐Q accurately estimates the cognitive stage among cognitively impaired older people (with high prevalence of comorbidities) in a primary care setting. This can aid primary care physicians in the diagnosis of cognitive impairment, clinical management/support, and as part of the work‐up for identifying eligible participants for anti‐amyloid treatment.