bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of tau‐PET tracers for in vivo Braak staging: the HEAD Study
Authors: Macedo Arthur C. , Therriault Joseph , Rahmouni Nesrine , Servaes Stijn , Wang Yi‐Ting , Tissot Cécile , Lussier Firoza Z , Arias Jaime Fernandez , Socualaya Kely Monica Quispialaya , Hosseini Seyyed Ali , Ferreira Pamela C.L. , Bellaver Bruna , Ferrari‐Souza João Pedro , Aguzzoli Cristiano Schaffer , Povala Guilherme , Pascual Belen , Gordon Brian A. , Lowe Val J. , Oh Hwamee , soleimani‐meigooni David N. , Baker Suzanne L. , Pascoal Tharick Ali , Rosa‐Neto Pedro
Published: January 2025

Background

Tau‐PET tracers allow for in vivo Braak staging of individuals in the Alzheimer’s disease (AD) continuum. The impact of tracers’ characteristics for Braak staging using tau‐PET remains unclear. Therefore, we performed a head‐to‐head comparison of Braak staging using first‐ and second‐generation tau‐PET tracers.

Method

We assessed 51 cognitively unimpaired (CU) and 49 cognitively impaired participants (mean [SD] age 69.4 [7.5] years) with at least two tau‐PET ligands ([18F]MK6240, [18F]AV1451, and/or [18F]RO948) at McGill University, as part of the HEAD study. We calculated standardized uptake value ratios (SUVR) in Braak‐like regions of interest (ROI) for each ligand and investigated their association using Spearman’s correlation. Thresholds defined the presence of tauopathy in each Braak ROI, which was used to assign a Braak stage to each participant. Finally, we assessed the agreement between the Braak staging provided by each tracer, both for the traditional (using separate Braak stages – 0, I, II, III, IV, V, and VI) and simplified (using joint Braak stages – 0, I‐II, III‐IV, and V‐VI) frameworks.

Result

In all Braak ROIs, we found positive correlations between the SUVR values of the three tracers (Figure 1). The strongest correlation was between [18F]MK6240 and [18F]RO948 in Braak II (r=0.94), and the weakest between [18F]AV1451 and [18F]RO948 in VI (r=0.51). Inter‐tracer agreement regarding the latest stage of abnormality was substantial or nearly perfect between pairs of tracers but moderate between the three tracers (Figure 2A). The simplified framework presented greater agreement compared to traditional Braak staging, except between [18F]MK6240 and [18F]RO948. At the ROI level, the lowest agreements were observed for Braak II and I‐II, when [18F]MK6240 and [18F]RO948 were compared to [18F]AV1451 (Figure 2B‐C). [18F]AV1451 had the highest probability of overestimating the Braak stage assigned by [18F]MK6240 and by [18F]RO948, especially at earlier stages (Figure 3).

Conclusion

The ligands presented moderate to nearly perfect agreement for in vivo staging of AD severity. Off‐target binding of [18F]AV1451 to the choroid plexus might explain disagreements at early stages. Overall, slight improvements in agreements were achieved with the simplified framework, as observed in histopathological staging.
DTI and DKI differences in the fornix microstructure associated with sleep apnea in cognitively normal patients
Authors: Figueredo Luisa F , Chen Jenny , Parekh Ankit , Bubu Omonigho M , Fieremans Els , Osorio Ricardo
Published: January 2025

Background

Obstructive sleep apnea (OSA) is a complex and heterogeneous condition associated with chronic physiological and neuropsychological disturbances (1–4). One notable neuropsychological effect observed in OSA patients is memory impairment (2,5). Additionally, some reports suggest that OSA may be associated with Alzheimer’s Disease (AD) (4). Memory consolidation is regulated through a cohesive network of structures, including the hippocampus, fornix, anterior thalamus, and mammillary bodies (6). Diminished mammillary body and hippocampal volume have been described in OSA patients compared to normal subjects, suggesting potential circuit changes (2). This study aims to comprehensively evaluate the effects of OSA on the fornix microstructure in cognitively normal patients, measured by DTI and DKI variables.

Methods

One‐night polysomnography, neurocognitive assessment, and brain diffusion MRI (dMRI) with DTI (Diffusion Tensor Imaging)/DKI (Diffusion Kurtosis Imaging) protocol were performed in 145 individuals with a mean age of 65 [61‐70] and a mean Mini‐Mental‐Score (MMSE) of 29 [28‐30]. OSA measurements included the Apnea‐Hypopnea Index (AHI) and variables related to sleep duration and fragmentation. Microstructural properties of white matter tracts (DTI. DKI (8–10)) were estimated after preprocessing dMRI using DESIGNER pipeline (https://arxiv.org/abs/2305.14445).

Results

A correlation matrix between AHI3% and AHI4% revealed positive correlations with Axial Kurtosis (AK) and axial diffusion (ADi), and negative correlations with Mean Diffusivity (MD) and Mean Kurtosis (MK). Figure 1C‐1D illustrates a significant difference between patients with and without OSA. Associations between AHI3% and AHI4% and log Fornix FA, MD, RD, ADi, MK, RK, AK, De″, De⊥ and Da were tested while adjusting for age, sex, hypertension, APOe4, BMI, and N1%, N3%. Unadjusted linear regression models appear in Figure 2, where only AK (Figure 2D), and MK (Figure 2F) showed statistical significance. Finally, multivariable‐adjusted models for AHI3% revealed a significant association with AK and MD only (Table 1).

Conclusion

OSA may be associated with microstructural changes in the fornix in cognitively normal patients, particularly in those with severe OSA. This study might contribute as a baseline for future works that include progression to AD.
AlzPED: An Open Science Tool to Increase Rigor in Therapeutic Efficacy Testing in Alzheimer’s Animal Models
Authors: Chakroborty Shreaya , Viswanathan Jaya , Gallofre Maria Fe Lanfranco , Martin Zane , Petanceska Suzana S , Refolo Lorenzo M
Published: January 2025

Background

Positive findings from testing therapeutics in AD animal models are often not translated to effective treatments due to the poor methodological rigor and inadequate reporting practices of therapeutic efficacy studies. The Alzheimer’s Disease Preclinical Efficacy Database (AlzPED), developed by the NIA, is a searchable and publicly available knowledgebase that prioritizes and promotes the use of rigorous methodology to ameliorate this translation gap. Through a checklist of experimental design elements – the Rigor Report Card ‐ AlzPED highlights reporting recommendations and standards while providing a practical tool to help plan rigorous therapeutic studies in animals. AlzPED also serves as a platform for creating citable preprints, including negative findings to mitigate the publication bias favoring positive reports.

Methods

Using key word‐driven literature searches published studies are acquired and curated by two subject‐matter experts for bibliographic details, funding source, study goals and principal findings, data on relevant translational criteria like therapy type, therapeutic agent, therapeutic target, animal models, and AD‐related outcome measures. Rigor is assessed with the Rigor Report Card.

Results

AlzPED hosts curated summaries from 1400 published preclinical therapeutic studies in AD animal models, and data related to 274 therapeutic targets, 1206 therapeutic agents, 226 animal models, more than 2500 AD‐related outcome measures, and thousands of principal findings. Evaluation of Rigor Report Cards from 1400 published preclinical therapeutic studies demonstrates significant under‐reporting of critical elements of methodology such as power/sample size calculation (4% of curated studies), blinding for treatment (10%), randomization (32%), balancing for sex (24%), inclusion/exclusion criteria (7%). All analytics are shared on AlzPED under the principles of open science.

Conclusions

Rigorous experimental design and transparent reporting are essential to inform future research, science policies, and successful clinical trials. Adopting a standardized set of best practices like those proposed by AlzPED can improve the predictive power of preclinical studies in AD animal models and promote the effective translation of drug testing data to the clinic.
Longitudinal Associations between Sensory Difficulty and Motor Impairment and Incident Dementia in the National Health and Aging Trends Study
Authors: Davoudi Anis , Dougherty Ryan J. , Wanigatunga Amal A , Agrawal Yuri , Wang Hang , Reed Nicholas S , Ehrlich Joshua R , Gross Alden L. , Schrack Jennifer A
Published: January 2025

Background

Impairments in sensory and motor function are common and have been independently linked with higher risk of dementia in older adults. Yet, there is limited information associated with the increasing number of such impairments and dementia risk. This study investigated longitudinal associations between sensory and motor impairment and dementia in older adults.

Method

We used data from the US National Health and Aging Trends Study (NHATS), a nationally representative cohort study of community‐living Medicare beneficiaries aged 65 years and older. Baseline sensory impairments were defined based on self‐reported vision and hearing loss indicators. Baseline motor impairments were defined based on performance in gait, repeated chair stands, standing balance, and grip strength tests. Multivariable Cox regression models were used to evaluate the hazard ratio of incident dementia from baseline (2011) to 2022.

Result

A total of 3847 participants without dementia at baseline were included (weighted mean age 73.9 (95% CI: 73.7‐74.1) years old and 56% (95% CI: 54.1‐57.9) female). Compared to those without impairment in each specific domain, hazard ratios for incident dementia were 1.02 (95% CI 0.89‐1.16, p = 0.82) for hearing impairment, 1.34 (95% CI 1.13‐1.60, p = 0.001) for vision impairment, 1.31 (95% CI 1.18‐1.47, p<0.001) for chair stand impairment, 1.23 (95% CI 1.10‐1.39, p<0.001) for standing balance impairment, 1.49 (95% CI 1.34‐1.67, p<0.001) for gait speed impairment, and 1.31 (95% CI 1.13‐1.51, p<0.001) for grip strength impairment (Table 1). Additionally, compared to participants with no impairments, the hazard ratio for incident dementia for those with three impairments was 1.44 (95% CI 1.14‐1.82, p = 0.003), with four impairments was 1.92 (95% CI 1.50‐2.47, p<0.001) and with 5‐6 impairments was 1.96 (95% CI 1.50‐2.56, p<0.001) (Table 1, Figure 1).

Conclusion

In this cohort study of US Medicare beneficiaries, vision and motor impairment as well as a higher number of impairments were associated with elevated risk of dementia. These findings underscore the cumulative burden of sensory and motor impairments on incident dementia. A better understanding of the temporality and longitudinal effect of sensory and motor impairments on incident dementia may help inform future targeted interventions.
The development and validation of the Alzheimer’s Disease Caregiver Reported‐Health Index (ADCR‐HI): a disease‐specific caregiver‐reported outcome measure for use in clinical trials
Authors: Shupe Christina , Seabury Jamison , Varma Anika , Weinstein Jennifer , Engebrecht Charlotte , Rosero Spencer , Irwin Charlotte , Dilek Nuran , Arky Abigail , Santos Elizabeth , Heatwole Chad
Published: January 2025

Background

In preparation for therapeutic trails involving patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI), there is a need for valid, disease‐specific caregiver‐reported outcome (CRO) measures capable of tracking symptomatic burden in response to therapy over time. CROs are useful tools in clinical trials for individuals with AD, MCI, and dementia who are unable to self‐report. In addition, CROs are accepted by the United States Food and Drug Administration to support regulatory claims. This research involved the development and validation of the Alzheimer’s Disease Caregiver Reported‐Health Index (ADCR‐HI): a regulatory grade, disease‐specific CRO for use in detecting symptomatic changes in individuals with AD, MCI, and dementia during therapeutic trials.

Method

We conducted semi‐structured qualitative interviews and a cross‐sectional survey with caregivers to identify the prevalence and relative importance of symptoms experienced by individuals with AD, MCI, and dementia. We selected symptom questions for the ADCR‐HI based on their relevance and potential responsiveness to therapeutic intervention. We performed beta interviews with caregivers to determine the comprehensiveness, ease of use, and relevance of the instrument. Subsequently, we determined the reliability, known groups validity (Figure 1), and final internal consistency of the ADCR‐HI. We additionally conducted an area under curve (AUC) analysis using ADCR‐HI total scores (Figure 2).

Result

Initial interviews were conducted with 15 caregivers of individuals with AD, MCI, or dementia. The cross‐sectional survey was completed by 324 caregivers. Beta interviews with 12 caregivers determined the instrument to be relevant and easy to use. The ADCR‐HI and its subscales displayed high test‐retest reliability over a 14 day period (n = 30) (Table 1). Known groups analysis (Figure 1) demonstrated the ability of the ADCR‐HI to differentiate between groups with greater disease severity.

Conclusion

The ADCR‐HI is a regulatory‐grade, reliable CRO comprised of eight subscales that comprehensively measure an individual’s symptomatic burden through the perspective of the caregiver. The ADCR‐HI is available to support therapeutic trials and drug‐labeling claims as a valid clinical tool.
The MindMoves Trial: Effect of Lifestyle Physical Activity and Cognitive Training Interventions on Cognition in Older Women with Cardiovascular Disease
Authors: Halloway Shannon , Arvanitakis Zoe , Schoeny Michael E , Volgman Annabelle Santos , Pressler Susan J , Vispute Sachin , Wilbur JoEllen , Barnes Lisa L.
Published: January 2025

Background

Cardiovascular disease (CVD) increases the risk of cognitive impairment (CI), particularly in women. Physical activity and cognitive training can improve cognition, with potential interactive effects. The purpose of this study was to evaluate the efficacy of MindMoves, a 24‐week multidomain physical activity and cognitive training intervention, on cognition in older women with CVD.

Method

This randomized controlled trial (NCT04556305) with a 2×2 factorial design tested the independent and combined efficacies of Mind (tablet‐based cognitive training) and Move (lifestyle physical activity with goal‐setting and group meetings) on change in cognition (episodic memory, semantic memory, working memory, and executive function). Women (n = 253) aged 65 years and older with CVD and without CI at baseline were randomized to (1) Mind, (2) Move, (3) MindMoves, or (4) usual care. Intervention orientations were in‐person, and all other intervention activities were home‐based. From September 2020–December 2023, participants completed telephone neuropsychological tests and questionnaires at baseline, 24, 48, and 72 weeks.

Result

Participants were, on average, 72.4 years old at baseline (range = 65‐90), primarily of non‐Hispanic White (54%) and non‐Hispanic Black (38%) racial backgrounds, and 60% graduated college. A total of 86% (n = 218) of participants completed the 72‐week data collection. Attrition was not a function of intervention condition, sociodemographics, or baseline cognition (all p’s > .05). On average, all participants showed improvement in episodic memory and executive function. In multilevel mixed models adjusted for age, education, and racial and ethnic background, the main effects of Mind and Move, and the interactive effects (Mind*Move interaction), on linear change over 72 weeks were not statistically significant for any of the four cognition outcomes. In additional models that tested the intervention effects averaged across all follow‐up timepoints, none of the intervention conditions were associated with cognition.

Conclusion

Although participants improved in two domains of cognition, there were no differential effects of the intervention conditions (cognitive training and/or physical activity) in this cohort of older women with CVD. Future analyses will examine intervention effects on serum biomarkers that may provide additional insights of efficacy.
State‐level effect of Medicaid expansion on Alzheimer’s disease and related dementias mortality
Authors: Wing Jeffrey , Rajczyk Jenna , Strominger Julie , Singh Parvati
Published: January 2025

Background

With the rapid aging of the US population, the prevalence of dementia is projected to double. The enactment of the Affordable Care Act and Medicaid expansion could create opportunities for detection and classification of dementia. There are trends of increasing dementia mortality, however, it is unknown whether Medicaid expansion increased the reporting of dementia as the underlying cause of death (UCOD) or as a multiple cause of death (MCOD) among the elderly.

Methods

State‐level Alzheimer’s disease and related dementias (ADRD) mortality data for those 65 years and older were downloaded from CDC WONDER for 2000‐2019. ADRD was classified as ICD‐10 codes: F01, F03, and G30. Staggered difference‐in‐difference analysis was done to estimate the ADRD mortality rate pre‐ and post‐Medicaid expansion. An overall average treatment effect for the treated (ATT) was estimated along with estimation for ATT by post‐period. Mortality measured as UCOD and MCOD were evaluated separately. Results were compared to all‐cause and cardiovascular disease (CVD) mortality for the same period.

Results

A total of 29 out of 50 states expanded Medicaid by 2019. Post expansion, ADRD mortality increased by 9.02 per 100,000 persons (95% CI: 1.81, 16.23). The change in mortality (UCOD) was most pronounced by two years post expansion, gradually increasing each year (two‐years post ATT: 10.02; 95% CI: 3.51, 16.52; five‐years post ATT: 13.58; 95% CI: 2.82, 24.34; Figure 1a). MCOD ADRD mortality demonstrated a similar pattern as UCOD ADRD mortality (ATT: 11.31; 95% CI ‐1.42, 24.05; Figure 2a). This trend was not observed across the same period for UCOD CVD mortality (ATT: 0.80; 95% CI: ‐12.42, 14.02) and the post‐expansion difference observed for UCOD all‐cause mortality lacked precision in comparison to dementia mortality (ATT: 7.43; 95% CI: ‐23.12, 37.98).

Conclusions

ADRD as the UCOD increased following state‐level Medicaid expansion, but this increase was not observed similarly for CVD mortality nor all‐cause mortality. Additionally, the same effect was not observed for ADRD as a MCOD. The lag between expansion and the increase in mortality may arise from increased detection through Medicaid supported care and in‐turn being listed or correctly identified as the underlying cause of death.
Physical activity and diet modify the sex specific association between neurotrophin single nucleotide polymorphisms and insomnia in late‐life
Authors: Gonzalez Hector L. , Schwartz Sarah , Rattinger Gail B. , Liu Yin , Drewel Mikaela , Mills Maddy , Buhusi Mona , Tschanz JoAnn T.
Published: January 2025

Background

Sleep disturbance is common in older adults at prevalence rates ranging between 30 ‐ 50% in the United States. Insomnia in late life is influenced by a wide array of genetic and lifestyle factors, some of which exhibit sex‐dependent effects. This study examined whether selected single nucleotide polymorphisms (SNPs) related to the neurotrophin, brain‐derived neurotrophic factor (BDNF), or its receptors and lifestyle factors, and their interactions were associated with the increased risk for sleep disturbance in older males and females.

Method

The Cache County Study on Memory and Aging, a longitudinal, population study, enrolled 4,057 cognitively healthy participants [56.7% female; mean (SD) age = 74.78 (6.75) years]. Sleep disturbance (39% endorsed) was determined by self‐report of insomnia. Adherence to the Mediterranean diet and physical activity (sedentary, light, moderate and vigorous) were based on mail‐in questionnaires. The following SNPs were examined as predictors of sleep disturbance in separate logistic regression models for males and females: rs6265 (BDNF Val66Met), rs56164415 (BDNF C270T), rs2289656 (NTRK2 receptor TrkB), and rs2072446 (NGFR p75NTR). Covariates included age, body mass index, education, APOE ε4 status, and depression.

Result

SNPs for BDNF or its receptors were not associated with sleep disturbance. Males experienced an 18% reduced odds of sleep disturbance with increasing levels of physical activity (OR (95%CI) = 0.83 [0.71; 0.97]; p = .023), whereas greater adherence to the Mediterranean diet was associated with an 8% higher odds of reporting sleep disturbance (OR [95%CI] = 1.08 [1.00; 1.18]; p = .047). Among females a trend for an interaction (p = .088) between Val66Met and physical activity indicated those with the minor allele who engaged in sedentary‐to‐light physical activity exhibited a 45% higher risk of sleep disturbance compared to those with the minor allele and moderate‐to‐vigorous physical activity (p = .026).

Conclusion

Lifestyle factors of physical activities and diet affect the BDNF gene‐insomnia association differently for older males and females. Future studies may further explore interventions affecting BDNF levels (e.g., physical activity) as one potential way to treat insomnia in older adults.
Lexicon of Dementia: A cross‐linguistic study of the impact of dementia terminology on cultural perceptions
Authors: Michael Mary Chi
Published: January 2025

Background

Language serves as a powerful tool in shaping perceptions and reinforcing societal norms. Current understanding suggests that the language used to describe dementia can impact how the condition is perceived, understood, and addressed within various cultural contexts. Further, language can play a pivot role in shaping caregiving practices, willingness to seek medical care, and the openness, or lack thereof, to speak about the condition. Understanding these linguistic nuances, both across and within, languages is critical for fostering more effective, inclusive, and tailored approaches to addressing dementia.

Method

To understand how language influences cultural perceptions of dementia, we conducted interviews with linguists, medical anthropologists, health care professionals, care partners, and individuals living with dementia across five languages: Japanese, Mandarin, Swahili, Spanish, and Portuguese. We discussed terminology, regional nuances in language, stigma, misconceptions, care practices, communication strategies, and paths forward for addressing language and improving cultural perceptions. Interviews were supplemented with a comprehensive review of existing literature.

Result

From our research we found that dementia terminology varies greatly across languages. In some, ‘dementia’ carries significant stigma, translating to ‘stupid’, ‘crazy’, ‘senile’, or other, similarly discriminatory terms. In other languages, there is no word for dementia at all, so the local language is mixed with English to describe memory or cognitive decline. Responses are similarly varied. Some cultures are making efforts to, or have already, changed discriminatory language around dementia. Others, particularly those without substantial dementia terminology, look to English to set a better standard.

Conclusion

Across languages, experts concede that dementia terminology is an integral factor in perpetuating stigma, misinformation, and silence. But it doesn’t have to be. Language can also be used to drive positive change. By exploring the connection between language and cultural perceptions, and by studying the measures some have taken to address linguistic stigma, we can uncover valuable insights that inform a broader dialogue on effective and inclusive language for dementia.
Direct and indirect costs of dementia in Brazil
Authors: da Mata Fabiana A F , Ramos Ari Alex , Bertola Laiss , Suarez Thais , Ferri Cleusa P , Júnior Haliton Alves de Oliveira
Published: January 2025

Background

In Brazil, the dementia landscape is projected to intensify significantly, with the number of people living with dementia expected to more than triple by 2050. This anticipated surge underscores the urgency for health and social systems to strategize and prepare adequately. However, studies about costs related to dementia are very scarce in Brazil, making it difficult to understand better the financial impacts of the syndrome. Estimating the direct and indirect costs related to dementia, considering the reality of Brazil in its geographical diversity, is essential to understanding the reality of health resource allocation and, therefore, (re)direct resources to meet better the needs of people with dementia and their families. This study aims to estimate costs related to dementia in Brazil.

Method

This study is part of the ReNaDe (National Report on Dementia) project, a domiciliary survey conducted with 140 dyads of people with dementia and their respective caregivers in 17 municipalities in Brazil. We used the cost of illness study methodology to estimate costs. We collected data from the ReNaDe interviews and national records and presented estimates from societal and the Brazilian Public Health Systems (SUS) perspectives. Our total costs encompassed direct medical costs (hospitalizations, outpatient visits, and others) and indirect costs (for instance, the monetary value of informal caregiving hours) (Table 1). We did not consider direct social costs, given limited or inexistent information about cost and services utilization by people with dementia in Brazil. We used the replacement approach to estimate indirect costs.

Result

The monthly cost of dementia per individual increases with the syndrome’s progression (Table 2). Indirect costs, primarily associated with informal care provided by family or friends, constitute at least 73% of total expenses, irrespective of dementia stage and adopted perspective. For Brazil in 2019, dementia’s total annual cost was US$18 billion, with indirect costs comprising 78%.

Conclusion

The average expenses per individual escalate with the advancement of dementia in Brazil. The pronounced prevalence of indirect costs accentuates the pivotal role that family caregivers assume in dementia care.
ß‐Hydroxy ß‐methyl butyrate, a muscle‐building supplement, restores neuronal plasticity in Alzheimer’s disease model
Authors: Paidi Ramesh Kumar , Pahan Kalipada
Published: January 2025

Background

Alzheimer’s disease is the most dreaded multifactorial neurological illness for which there is currently no known treatment. Although the exact cause of AD is still unknown, several factors related to lifestyle, genetics, and environment are known to have a significant role in the disease’s development. Alzheimer’s disease is characterized by neuronal loss, neurofibrillary tangles, and senile plaques. Still, synapse loss is thought to be a major neuropathology associated with AD. β ‐hydroxy β ‐methyl butyrate (HMB) is a common muscle‐building supplement used by bodybuilders to enhance exercise‐induced increases in muscle development and strength. HMB is an extremely safe supplement that shows no negative effects even after prolonged use.

Method

In primary mouse hippocampal neuronal cultures, we first validated the effect of HMB in terms of neuronal plasticity and neuronal markers. Additionally, we gave six‐month‐old XFAD animals oral HMB for 30 days, and we used the T‐Maze, Barnes Maze, Novel Object Recognition, and locomotion tests to evaluate the animals' cognitive skills. In vivo pathway inductions were analyzed using western blotting and immunohistochemical studies.

Result

In the current study, HMB treatment prominently elevated neuronal plasticity markers like Glut N2A, Glu‐A1, Snap25, and PSD 95 in primary hippocampal cultures. HMB restores the cognitive malfunctions in 5xFAD AD mice; SNAP25 and PSD 95 expressions were increased following HMB administration. This was consistent with the phosphorylation of CREB and the increased calcium influx in the hippocampal region implicated in improving synaptic plasticity.

Conclusion

Our results indicate that HMB increases the expression of synaptic proteins and controls CREB phosphorylation, which could regulate neural plasticity and lead to cognitive recovery in AD models. Given that HMB is a strong, safe supplement, more research on its potential benefits for treating AD seems needed.
Self‐Reported Dementia Risk for People with Parkinson’s Disease Identifying as Sexual and Gender Minorities
Authors: Bayram Ece , Banks Sarah
Published: January 2025

Background

People identifying as sexual and gender minorities (SGM) may have higher risk for subjective cognitive decline and Alzheimer’s disease, although the risk for Parkinson’s disease dementia (PDD) has not been investigated. Male sex is associated with a higher risk for PDD, it is unclear whether SGM status impacts the risk.

Methods

Data were obtained from Fox Insight on April 5th, 2023. The analysis included people (1) with adult‐onset Parkinson’s, (2) responding to questions on sex assigned at birth, gender identity, sexual orientation, (3) with at least one available Penn Parkinson’s Daily Activities Questionnaire‐15 (PDAQ‐15), (4) without dementia at baseline, based on the first PDAQ‐15 (>43). Groups consisted of people identifying as (1) SGM with female sex assigned at birth (SGM‐F, n = 75); (2) cisgender, heterosexual women (CHW, n = 2,046); (3) SGM with male sex assigned at birth (SGM‐M, n = 84); (4) cisgender, heterosexual men (CHM, n = 2,056). Sex assigned at birth and SGM status effects on dementia likelihood during follow‐up were assessed with generalized linear mixed models.

Results

Out of 159 people identifying as SGM, eight (5.0%) identified as gender minorities, 144 (90.6%) identified as sexual minorities, seven (4.4%) identified as both gender and sexual minorities. At baseline, people with female sex had better PDAQ‐15 scores than people with male sex assigned at birth; SGM‐M had the lowest scores. SGM‐M had a higher dementia likelihood compared to people not identifying as SGM. After adjusting for age, education, employment status, income, perceived discrimination level, age at Parkinson’s diagnosis, baseline PDAQ‐15 scores, that differed across groups at baseline, dementia likelihood was lower for CHW compared to people with male sex assigned at birth.

Conclusions

For PDD, SGM‐M can be at a higher risk than CHM; people with female sex can have a lower risk than people with male sex assigned at birth. Socioeconomic disadvantages can alter the sex effect on PDD risk, by putting SGM‐M at a higher risk and females at a similar risk level compared to people with male sex assigned at birth, as shown in unadjusted models. Socioeconomic disadvantages should be acknowledged and addressed to support the well‐being of SGM with Parkinson’s.
Caregiving Concerns in Lewy Body Dementia
Authors: Bayram Ece , Patel Bhavana , Stacy Kelly E , Farley Morgan , Bedenfield Noheli , Taylor Angela , Wood Julia M , Armstrong Melissa J , Holden Samantha K. ,   Lewy Body Dementia Association Community Engagement Group
Published: January 2025

Background

Lewy body dementia (LBD) is a common and burdensome neurodegenerative dementia, that remains under‐recognized and under‐studied. Caregivers play an important role, although research on their needs is lacking. Understanding and addressing their concerns can help improve their well‐being, the care they provide for their loved ones, and also participation in research.

Methods

Between April 7, 2021, and July 1, 2021, we queried the research priorities, symptom burden, gaps in care, and concerns of people with LBD, and caregivers of people with LBD through forced ranking in an anonymous 15‐20 minute web‐based survey. It was designed by the LBD Association Research Centers of Excellence Community Engagement Working Group and distributed by the LBD Association.

Results

Participants included 832 caregivers (550 current, 280 former, 2 did not specify) with the majority caring for their spouse/partner (63%). They were most likely to be 70‐79 years old (33.5%), married/in a domestic partnership (71.3%), have a bachelor’s or graduate degree (32%, 34.2%), identify as woman (84%), and White (93.4%). Current caregivers were caring for a person who had been diagnosed within the past year (28.4%). Formal caregivers reported their loved one most likely died within the past year (37.5%). Overall, 80% had not participated in research previously. They were frequently concerned about how to manage caregiving alongside other responsibilities (50.1% on a daily basis), what to expect with disease progression (49.7% on a daily basis), how to handle behavior changes (45.9%), and how to support the independence of their loved one (42.6%). They were least concerned about how to obtain medical care for themselves; 34.9% never experienced this concern.

Conclusions

Caregivers of people with LBD experience multiple concerns on a daily basis. Providing support, creating resources, and raising awareness about the available resources can benefit both the caregivers and their loved ones with LBD. Although our cohort was not diverse and the results should not be generalized, our findings can guide future efforts to include caregivers in clinical care, education, and research. Caregivers can provide invaluable information regarding their loved one’s state, the effectiveness of treatments, and the feasibility of research studies.
Cellular Automata Framework for Classification of Cognitive Impairment from Clinical Dementia Rating
Authors: Kesu Siva Manohar Reddy , Sinha Neelam , Ramasangu Hariharan
Published: January 2025

Background

Clinical Dementia Rating (CDR) and its evaluation have been important nowadays as its prevalence in older ages after 60 years. Early identification of dementia can help the world to take preventive measures as most of them are treatable. The cellular Automata (CA) framework is a powerful tool in analyzing brain dynamics and modeling the prognosis of Alzheimer’s disease.

Method

The proposed algorithm uses the CA framework to construct features for the classifier for the classification of classes in the dataset. A subject is assigned to a CA cell grid based on its feature values as rows and the specified number of cells in each row. When a CA grid receives a feature from a subject, the feature values are distributed among the cells using a transfer function. The distribution of featured values in the CA grid from the initialized cell to the neighboring cells in the row with a diffusion rate of 20%. Hence, redistributed CA images have been obtained for all the subjects. Deep learning architecture constituted with 4 layered Conv2d has been modeled for the classification of the CA images to classify low, moderate, and severe cognitive impairment.

Result

CDR from the ADNI dataset comprising 1948 subjects has been preprocessed for the six features and three classes (i.e., Low, moderate, and severe cognitive impairment) with 70% train sets and 30% test sets. A balanced dataset of 89 subjects for moderate and severe cognitive impairment has given the classification accuracy of 96%. A balanced dataset of 363 subjects for low and moderate cognitive impairment has given the classification accuracy of 95%.

Conclusion

A CA framework for the classification of cognitive impairment has been achieved with good accuracy. The implementation of the CA approach and its runtime performance has an advantage over the well‐known algorithms by giving a good pathway in contributing to the classification problems.
Factors influencing frailty in older adults admitted to a tertiary level hospital of Nepal
Authors: Shrestha Prabha , Shakya Sarina , Acharya Radha
Published: January 2025

Background

Frailty is significantly associated with incidence of Alzheimer’s disease and dementia and death (1). The worldwide incidence of frailty and pre frailty was estimated as 43.4 and 150.6 new cases per 1000 person‐years, respectively(2). Risk of frailty is high in Low and Middle Income countries (3) 65%‐71% of the community dwelling older adults had reported frailty in Nepal(4). We aimed to find out the frequency of frailty and it’s associated factors in older adults admitted to a tertiary level hospital of Nepal.

Method

We conducted a cross sectional analytical study with the estimated sample size of 109. Ethical approval was obtained from ethical review committee Kathmandu University School of Medical Sciences. Data were collected from the older adults admitted to general wards via face to face interview after obtaining informed consent. Frailty was assessed by Groningen Frailty Index (GFI) which has total score of 15 and the participants scoring four or more were considered frail (4). Binary logistic regression analysis was done to examine the association between independent variables and frailty.

Result

Total 109 older adults participated in the study. The mean age was 72.5 (60‐90) years. Half of the participants (51.4%) were male. Nearly two third (60.6%) among them met the criteria of frailty. Mean score of frailty was 4.9 with SD 3.55. On the Binary logistic analysis, the model predicted frailty with 38% of variance (Nagelker R Square = 0.38) in the outcome. Female were at risk of frailty with odd ratio of 3.48 (p = .014) history of fall within a year predicted frailty with odd ratio 4.24 (p = .043) and the people who perceived their health as good reduced the risk of frailty with odd ratio 0.34 (p = 0.10). However, age, presence of chronic illness and number of daily drug consumption could not predict frailty in this population.

Conclusion

These result raise red flags for the incidence of dementia in Nepal, as frailty is a notable precursor to worsening cognitive status. Timely management of frailty in Nepal is imperative. Further research is needed to identify the best ways to address frailty in this setting.
Are women at a higher risk of dementia? A National Study of Underlying Background Medical Conditions
Authors: Rotstein Anat , Kodesh Arad , Levine Stephen Z
Published: January 2025

Background

Studies of the association between sex and the risk of incident dementia are inconsistent, in part conceivably due to sex‐specific background medical conditions.

Method

A prospective national cohort study which consisted of 112,204 members of a nonprofit Israeli health maintenance organization born between 1902 and 1952 who entered the cohort on January 1, 2002, without a dementia diagnosis and were followed up to January 1, 2020. Participants were aged 50 to 100 years. Incident dementia was ascertained based on medical diagnoses with International Classification of Diseases codes from the Ninth (331.0‐331.9) and Tenth (F00–F03) revisions. Cox regression models were fitted to quantify the association between sex and the risk of incident dementia with Hazard Ratios (HR) and their 95% Confidence Intervals (CI) unadjusted and adjusted for 34 sources of potential confounding.

Results

Women had a higher unadjusted risk for dementia. After adjustment for two demographic factors (birth year and socioeconomic status) and 32 medical conditions (psychiatric disorders, musculoskeletal system, and connective tissue disorders, metabolic syndromes, cardiovascular diseases, respiratory diseases, neurological diseases, genitourinary, digestive, malignant diseases, and injuries) the association between sex and dementia was no longer significant.

Conclusion

The commonly reported increased dementia risk for women does not extend once a history of selected medical conditions is considered, suggesting that a more focused outlook on the association between sex and dementia may be a step forward in the identification of at‐risk groups and dementia prevention.
Later‐life cognitive and behavioral changes in older adults with Long COVID
Authors: Azhar Sabika , Guan Dylan X. , Smith Eric E. , Ismail Zahinoor
Published: January 2025

Background

Individuals diagnosed with COVID‐19 may continue to experience symptoms long after infection. Research suggests that the COVID‐19 virus may be linked to brain pathology and dementia risk, possibly due to neurological complications and long‐term cognitive effects. Mild Behavioral Impairment (MBI) is an early indicator of dementia risk characterized by later life onset of persistent changes in behavior or personality. To better understand the consequences of COVID‐19 on older adults, we investigated whether older adults who experienced Long COVID reported more severe later‐life emergent cognitive and behavioral symptoms linked to elevated dementia risk.

Method

Participants were from the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behavior, Function, and Caregiving in Aging (CAN‐PROTECT), who self‐reported testing positive for COVID‐19 (n = 684), stratified by whether they reported having Long COVID. The severity of subjective cognitive symptoms was measured with the Everyday Cognition scale (ECog‐II). The severity of MBI symptoms was measured with the MBI Checklist (MBI‐C). We modelled associations between Long COVID (exposure) and ECog‐II or MBI‐C total scores using negative binomial regression models (zero‐inflated, if appropriate), adjusting for age, sex, education, ethnocultural origin, marital status, employment status, and number of vaccine doses administered.

Result

Participants (81.7% female, mean age 63.7±7.3 years) who experienced Long COVID (n = 41) reported an ECog‐II total score 1.73 times higher (95% CI: 1.32‐2.32, p ≤0.001), and an MBI‐C total score 2.18 times higher (95% CI: 1.46‐3.22, p≤0.001) than those without Long COVID. Effect sizes differed for each of the ECog‐II and MBI‐C domains (Table 2). The greatest magnitude of effect was seen in the executive function domain for ECog‐II with a 2.32 times greater score (95% CI: 1.57‐3.60, p≤0.001), and psychotic symptoms domain for MBI with a 3.49 times higher score (95% CI: 1.57‐7.92, p = 0.002), compared to those without Long COVID

Conclusion

Among older adults who tested positive for COVID‐19, those who experienced Long COVID symptoms reported more severe cognitive and behavioral symptoms that indicate elevated risk for dementia. Future studies should investigate symptoms over time and mechanisms linking Long COVID with potential prodromal cognitive and behavioral symptoms for dementia.
The associations of body shape and composition with incident dementia and cognitive changes
Authors: Wu Zimu , Owen Alice , Woods Robyn , Cribb Lachlan , Zhou Zhen , Chong Trevor T.‐J. , Orchard Suzanne , Shah Raj C. , Wolfe Rory , McNeil John J , Sheets Kerry M. , Murray Anne , Ryan Joanne
Published: January 2025

Background

Although the importance of body weight in later life for brain health has been established, less is known about body shape and composition. This study aims to examine their associations with dementia and cognitive changes in older adults.

Method

Data were obtained from over 17,000 community‐dwelling individuals aged 65‐98 years, recruited in Australia and the US. We assessed body shape using the ratio of waist circumference to body mass index (WBR), and estimated lean (LM) and fat mass (FM) by the Hume formula. Dementia diagnosis was adjudicated according to DSM‐IV. Global cognition, verbal fluency, episodic memory, and psychomotor speed were assessed annually for 11 years. Cox regression and mixed‐effects models were used respectively, to estimate the associations with incident dementia and cognitive changes over time.

Result

A higher WBR was associated with higher dementia risk in men (HR: 1.41, 95% CI: 1.04‐1.93, p = 0.03), and with greater decline in all cognitive tests in both genders (coefficients: ‐0.123 to ‐0.030, all p‐values<0.05). Conversely, lower dementia risk was shown in greater LM (men, HR: 0.97, 95% CI: 0.95‐0.99, p<0.001; women, HR: 0.96, 95% CI: 0.95‐0.98, p<0.001) and FM (men, HR: 0.62, 95% CI: 0.48‐0.80, p<0.001; women, HR: 0.63, 95% CI: 0.49‐0.81, p<0.001). Also, they showed slower decline in global cognition, episodic memory, and psychomotor speed (coefficients: 0.002 to 0.007, all p‐values<0.05).

Conclusion

Higher body weight in later life, independent of composition, may benefit brain health. However, increased abdominal fat poses risks for cognitive impairments.
The neuroprotective properties of GLP‐1R agonists correlate with their ability to cross the blood‐brain barrier
Authors: Holscher Christian
Published: January 2025

Background

Glucagon‐like peptide 1 (GLP‐1) is a peptide hormone that plays several physiological roles in treating diabetes and in protecting the brain. Recent clinical trials testing 4 different GLP‐1 class drugs in phase 2 trials showed a clear correlation between neuroprotection and the ability to cross the BBB. Exenatide and Lixisenatide both showed excellent protective effects in patients Parkinson’s disease (PD) and both drugs can readily cross the BBB. Liraglutide showed limited effects and can only cross the BBB at a low rate. A pegylated form of exenatide NLY01 did not show any effects in a clinical trial and the drug does not cross the BBB.

Method

We tested a novel dual GLP‐1/GIP agonist that can cross the BBB easily and compared it to Semaglutide, a GLP‐1 class drug on the market to treat diabetes in the 3xFAD tg mouse model of AD. Water maze tests and in vivo electrophysiology had been conducted, and synapses quantified using the GOLGI method. Biomarkers were analyzed by histology and western blot to test for inflammation.

Result

In a direct comparison, the dual agonist was superior to Semaglutide in improving learning and memory, in vivo LTP in the hippocampus, activation of microglia and release of pro‐inflammatory cytokines. Synapse numbers were enhanced by both drugs.

Conclusion

The results demonstrate that enhanced BBB penetration of GLP‐1 class drugs shows superior neuroprotective effects in a 3xtg mouse model of AD. This mirrors the observations from clinical trials in PD patients that show enhanced protection with drugs that can cross the BBB better.
The Role of Cerebral Small Vessel Disease Burden in Idiopathic Normal Pressure Hydrocephalus: Insights from a Prospective Cohort Study
Authors: Cai Hanlin , Huang Keru , Yang Feng , Hu Na , He Jiaojiang , Gao Hui , Feng Shiyu , Qin Linyuan , Wang Ruihan , Wang Shan , Liao Qian , Liu Yi , Zhou Liangxue , Zhou Dong , Hao Zilong , Chen Qin
Published: January 2025

Background

The pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) remain unclear. The cerebral small vessel disease (CSVD) pathology may play a crucial role in patients with iNPH. This study aims to investigate the prevalence of CSVD in patients with probable iNPH and examined the associations between CSVD burden and clinical characteristics and prognosis after shunt surgery.

Method

We enrolled patients with iNPH from an ongoing prospective cohort study in the West China Hospital of Sichuan University from August 2021 to present. The clinical characteristics, cognitive assessment, quantitative gait analyses, and MRI were prospective collected. Those patients who underwent shunt surgery were followed up at 3 months after. CSVD imaging markers including the CSVD burden, PWMH Fazekas, DWMH Fazekas, BG‐EPVS, and CSO‐EPVS scores, and the presence of lacunes and CMBs were evaluated. The linear and logistic regression models were used to investigate the association between the CSVD imaging markers and clinical features and outcomes in patients with iNPH.

Result

Among the 65 patients with iNPH (Age: 74.82 ± 6.23 years, Male: 69%), 83% (54/65) patients had at least one type of CSVD imaging markers and 63% (41/65) patients had CSVD score≧2. Age and hypertension were the highest risk factors. The CSVD score was associated with poorer Stroop test scores, a shorter stride length, lower step height, a faster cadence, and a longer Timed‐Up and Go test time. Adjusting for age, sex, years of education, and vascular risk factors, it remained associated with a shorter stride length. The CSVD score had increased trends for poor improvement in patients with shunt surgery.

Conclusion

Our study showed the high occurrence of CSVD imaging abnormality in patients with iNPH, and the comorbid CSVD were associated with more severe gait disturbances and cognitive decline, suggesting that CSVD may be involved in the pathogenesis of iNPH.