bluuebunny/crossref_metadata_2025 huggingface dataset:
Unmet need and public financing of home care in England
Authors: Adrion Emily R
Published: December 2023

Background

Persons living with dementia often wish to remain in their own homes for as long as possible. Given the unpredictable nature and progression of dementia, this means that many adults will require some degree of home‐based support in the initial stages of the disease, as well as requiring continuous, intensive support in the later stages. Public financing can play a central role in ensuring equitable access to home care, however, public financing is limited in many nations due to the high cost of these services. Without consistent government financing, many vulnerable adults may forgo needed care, risking adverse outcomes. In this study, we seek to examine unmet need and the role of public financing of home care among English adults over 50.

Method

Drawing on waves 6‐9 (2013‐2019) of the English Longitudinal Study of Ageing, we use longitudinal fixed effects and pooled cross‐sectional models to understand patterns and predictors of unmet need for home care support services. We focus particularly on the type of home care received, differentiating between publicly financed and/or provided care, privately paid formal care, and informal home care services. We also differentiate between unmet need, where no help is received, and ‘under‐met’ need, where help is received but it does not fully meet the needs of the care recipient.

Result

Worsening cognition and greater limitations in activities of daily living (ADL) and instrumental activities of daily living (IADL) are associated with fewer entirely unmet needs. Receipt of publicly financed and/or provided care is also associated with fewer unmet needs as compared to receiving informal and/or formal privately paid care. However, shifting from publicly financed/provided home care to exclusively informal and/or formal privately paid care is associated with lower odds of under‐met need, where the help provided does not fully meet the home care support needs of the recipient.

Conclusion

Greater ADL and IADL limitations and worsening cognition may trigger access to home care support services. Public financing/provision of home care may guard against needs going entirely unmet, however, the care that is received may not fully meet the support needs of those with dementia.
Hub brain regions for the remote spatial association between tau and Amyloid‐β proteins
Authors: Hojjati Seyed Hani , Feiz Farnia , Nayak Siddharth , Shteingart Jacob , Ozoria Sindy , Picha Saman Gholipour , Fernández Antonio , Devanand Davangere P. , Luchsinger Jose A , Stern Yaakov , Razlighi Qolamreza R
Published: December 2023

Background

The pathology of Alzheimer’s disease (AD) is characterized by two types of proteins: intracellular neurofibrillary tau tangles and extracellular β‐amyloid (Aβ) plaques. In the present observational studies, spatial discrepancies between these two proteins across the brain regions are well‐documented. However, the association between these two proteins remains elusive in different stages of depositions.

Methods

We aimed to investigate the remote association between tau and Aβ uptakes by using 572 elderlies 67.11 ± 6.08 (476 healthy control (HC) and 96 mild cognitive impairments (MCI)) Aβ and tau positron emission tomography (PET) scans. We leveraged 47 tau‐PET and 97 Aβ‐PET scans of healthy young individuals (aged 20‐40) to find the regional cut‐points for 68 cortical regions in the brain. Then by using these cut‐points and tau PET scans of all elderly individuals, we identified four groups of individuals (no tau phase, pre‐acceleration phase, acceleration phase, and post‐acceleration phase) (Table 1). Finally, a regional multiple linear regression model is performed for each group to detect the hubs region based on the remote association between each target region of tau and all other regions Aβ in the different phases of tau accumulations (controlling for gender, age, intracranial volume, and each target region Aβ).

Results

First, we show that the left and right entorhinal cortex, and right parahippocampal tau are the hubs of remote association with Aβ in several cortical regions (especially temporal regions) in the early stage of aggregation (Figure 1). Second, we identify tau in the same regions, continuing to demonstrate the highest remote associations with cortical Aβ (Figure 2) in the acceleration phase.

Conclusion

The remote association appears in medial temporal lobe (MTL) tau during the early stage, as well as the later stage of tau accumulation (pre‐acceleration and acceleration phases). While the cellular mechanism of remote association is still elusive, in vivo studies have demonstrated that the Aβ triggers tau deposition indirectly in distal regions. Understanding the association between tau and Aβ at the preclinical stage of AD is critically important for a better consideration of tau spreading, especially in disease‐related brain regions.
The Effect of Telomere Length on Gray Matter Volume Change and Cortical Thickness
Authors: Yetim Ezgi , Topcuoglu Mehmet Akif , Kutlay Nuket Yurur , Tukun Ajlan , Oguz Kader Karli , Arsava Ethem Murat
Published: December 2023

Background

Telomeres are specific nucleotide repeats that play an important role in preventing DNA damage during cell division. Telomere length holds promise as a predictor for age‐related diseases. However, the relationship between leukocyte telomere length and structural changes in the brain is not well understood. The aim of this study is to evaluate the cross‐sectional and longitudinal relationship between telomere length, structural features of the brain, and to examine the interindividual differences in age‐related brain atrophy within the framework of biological age.

Methods

A total of 202 individuals ≥50 years of age without any neurological complaints were included in the study. Telomere length measurements from the peripheral blood leukocytes and brain magnetic resonance imaging (MRI) were performed in all participants. Forty‐six of the individuals without any major health events during the follow‐up period were evaluated with a second structural brain MRI after an average of 4.7 years. The relationship between global gray matter volume change and telomere length was investigated with multivariate models. In addition, longitudinal surface‐based analysis was used to determine the relationship between telomere length and cortical thinning regionally.

Results

The mean (standard deviation) age of the population was 65.9 (8.6) years; female gender constituted 60.9% of the cohort. The mean telomere length was 7.5 (2.0) kB. Telomere length was not significantly associated with brain volumes and cortical thickness. However, in the longitudinal phase of the study, we found a negative correlation between basal telomere length and the rate of total gray matter volume decrease over time (r = ‐0.370; p = 0.012). This significant relationship persisted after adjusting for age, gender, follow‐up time, and baseline total gray matter volume (Standardized β = ‐0.286, p = 0.05). Longitudinal surface‐based image analysis also revealed a negative association between telomere length and left superior parietal cortex thickness, which remained significant after cluster correction.

Conclusion

Telomere length might be a predictor of age‐dependent structural changes in the brain. The left superior parietal cortex, in particular, tended to possess a vulnerability in this interplay.
The role of psychosocial factors on cognitive test outcomes among cognitively unimpaired African American women
Authors: Gracia Fernando I , Aguilar Alejandra , Large Stephanie E , Hall James
Published: December 2023

Background

Previous research shows that chronic stress and depression have deleterious effects on cognition. African American (AA) women disproportionately experience higher rates of poor mental and physical health outcomes, and a growing body of research links chronic stressors to these inequities. In AA’s, Subjective Cognitive Concerns (SCC) have not been widely studied and may be an early indicator of cognitive decline. This study aims to investigate the effect of psychosocial factors such as chronic stress, depression, and SCC on cognitive test outcomes in cognitively unimpaired AA women.

Method

Data from 232 cognitively unimpaired AA women were collected from the Health and Aging Brain Study: Health Disparities, a community‐based epidemiological study of aging. To assess chronic stress, we used the Chronic Stress scale. Depression was accessed via Geriatric Depression Scale (GDS). SCC, which is an algorithm‐derived variable was used to classify participants as either having or not having SCC. Linear regressions were calculated with cognitive test scores as the outcome variable and chronic stress, GDS, age, education, and SCC as predicting variables. The cognitive tests included Weschler Memory Scale ‐III Logical Memory (LM) 1 & 2, Trail Making Test (TMT) Part ‐ A & B, and Digit Span (DS). For each significant linear regression, structure coefficients were calculated.

Result

All linear regression models were statistically significant, ranging from LM1, LM2, TMT A & B p < 0.001 to DS p = 0.005. In LM1, structure coefficients demonstrated that education was the only significant factor correlated with the effect in the model. For TMT A and B, education and age were significantly correlated. LM2 and DS establish a different pattern with GDS, and education significantly correlated with the effect. Stress was also significantly associated with the effect on DS.

Conclusion

The results demonstrate in cognitively unimpaired AA women, the GDS scores were related to decreased performance across multiple memory measures (DS and LM2). Chronic stress may be related to reduced performance in working memory. In AA women, future research should examine the relationship between discrimination, chronic stress, affective symptoms, and allostatic load on cognition. Early interventions targeting psychosocial factors may improve care for diverse communities.
A prospective study investigating the relation between blood‐based biomarkers for Alzheimer’s disease and diagnosis/patient management in primary care: The CANTATE‐PC study
Authors: Claessen Thomas , Vigneswaran Sinthujah , Verberk Inge M.W. , den Braber Anouk , Smit Maartje , Wilson David , Nierman Melchior C. , Kooren Jurgen A. , van der Flier Wiesje M. , van Harten Argonde C. , Teunissen Charlotte E.
Published: December 2023

Background

With the advent of disease‐modifying therapies, the need for accurate and cost‐effective diagnosis of Alzheimer’s disease (AD) is high. As the first step in the patient journey, the general practitioner plays an essential role in the diagnostic process. Accurately diagnosing AD in primary care is challenging, because early signs of AD frequently go unrecognized and other forms of dementia may be misdiagnosed as AD. We aim to take a first step towards identifying the utility of a panel of 5 blood‐based biomarkers for AD in primary care, assessing the relation between AD plasma biomarkers, diagnosis and patient management.

Method

Clinical Implementation of Amyloid Neurodegeneration and Tau testing in primary care (CANTATE‐PC) is a prospective study conducted in the Netherlands. CANTATE‐PC aims to enroll 400 participants > 50 years old who present to primary care with cognitive complaints or behavioral changes. Patients with known alcohol or drug abuse are excluded (figure 1). Participants are recruited from 20 primary care practices. At baseline demographic data, medical data and questionnaires regarding global cognitive performance, the nature and severity of cognitive complaints, and iADL are collected from participants (table 1). After enrollment, The general practitioner answers 5 questions about their working diagnosis, patient management and the utility of plasma biomarkers for AD for this individual patient via an online questionnaire, both at baseline and after 6 months. Blood is collected via venipuncture, performed at home or at a local laboratory. Amyloid‐beta42/40 ratio, hyperphosphorylated tau, glial fibrillary acidic protein and neurofilament light are analyzed using Single Molecule Assays (SiMoA, Quanterix Corp.). Primarily, we assess the association between plasma AD biomarkers as predictors and working diagnosis and patient management as outcome measures. Our secondary outcomes are (a) to ascertain if diagnosis and patient management differ between patients with and without plasma evidence of underlying AD (b) to explore associations between plasma biomarkers and the severity of cognitive complaints, global cognitive performance and functioning in iADL and to (c) qualitatively identify scenarios where plasma biomarkers can improve current care.

Result

None

Conclusion

This is the first step towards providing clinical relevance for AD plasma biomarkers in primary care.
Single‐nuclei RNA sequencing provides evidence for glial senescence in Alzheimer’s disease
Authors: Fancy Nurun N , Smith Amy , Tsartsalis Stergios , Muirhead Robert , Chau Vicky , Davey Karen , Mcgarry Aisling , Khozoie Combiz , Willumsen Nanet , Zhang Xiaowen , Jackson Johanna , Matthews Paul M , Jenkyns Marion
Published: December 2023

Background

Ageing is the greatest risk factor for Alzheimer’s disease (AD). While accumulation of senescent cells is one of the major hallmarks of ageing, the effect of the senescence burden is yet to be explored in AD. The aims of this study were to i) quantify senescent microglia, oligodendrocyte and astrocyte in human brain in AD, ii) determine the driver of cell senescence in AD, and iii) AD pathology associated senescence.

Method

We multiplexed Image Mass Cytometry (IMC) to co‐localise cell type markers (IBA1, OLIG2, GFAP), senescence markers (GLB1 and p16) and β‐amyloid (4G8) to detect senescence in tissues from Middle Temporal Gyrus (MTG) of 10 AD and 10 non‐disease control (NDC). We also generated snRNA‐seq from three different brain regions of the same subject namely Entorhinal (EC), MTG (Mid‐temporal Cortex) and Somatosensory Cortex (SSC) of 9 AD and 9 NDC. We performed geneset enrichment analysis using a set of curated senescence associated genesets in snRNA‐seq using AUcell and dream (variancePartition). We further performed trajectory analysis using Monocle3 to characterise β‐amyloid associated senescence signatures in the snRNAseq data.

Result

More than 25% microglia, oligodendrocyte and astrocyte were positive for GLB1 in AD brains while only around 5% glia showed GLB1 expression in NDC. Around 25% peri‐plaque microglia within 10 µm around β‐amyloid plaques in AD showed expression of GLB1 while only 3% of microglia >10 µm had associated senescence markers. Senescence genes were significantly upregulated in AD compared to NDC and were positively correlated with increase amyloid densities in all three glial cells (not in neurons). Trajectories of the glial nuclei described increased expression of pathways related to replicative senescence, cellular activation and stress response in microglia and oxidative stress in oligodendroglia, and astrocyte. Senescence gene signatures were positively associated with both β‐amyloid and pTau.

Conclusion

Our results highlight the high burden of senescent glia and provide evidence for distinct mechanisms of senescence in microglia (both replicative and stress‐induced) relative to oligodendroglia and astrocyte (stress‐induced) in AD. Both β‐amyloid and pTau associated increase in senescence gene signatures suggest that senescence is an important feature in the late stage of AD.
Functional connectivity changes in subjects at risk of developing Alzheimer’s disease
Authors: García‐Colomo Alejandra , Nebreda Alberto , Carrasco‐Gómez Martín , de Frutos Jaisalmer , Toraño Federico Ramirez , Bruña Fernández Ricardo , Maestú Fernando
Published: December 2023

Background

Alzheimer’s disease is currently diagnosed after sufficient cognitive impairment and clinical dysfunction are manifest. The underlying neurological damage and dysfunction at that point are vast and extensive, and the processes behind it have been going on for decades. Consequently, recent research has been focused on the identification of early biomarkers.

The initial damage induced by the increase in Aβ levels manifests as neuronal hyperexcitability that translates to network alterations and an early hypersynchrony.

For this study, we used magnetoencephalography (MEG) to measure changes in neuronal activity of cognitively unimpaired adults (50‐80 y/o) at different levels of risk of developing AD. We also measured plasma levels of p‐tau231, a novel biomarker known to increase very early in the pathological continuum of the disease.

The main objective was to evaluate longitudinal changes in the connectivity of three regions known to be affected in the progression of AD, and which, according to previous studies, exhibit hyperconnectivity in subjects at greater risk of AD.

Method

69 subjects with family history (FH+) of AD and 28 individuals with no history (FH‐) were included in the study. A CBPT was used to measure longitudinal connectivity changes, and significant clusters were correlated with p‐tau231 levels.

Result

The FH+ results show significant clusters of longitudinal change that closely resemble those obtained by Ramírez‐Toranõ et al. (2021). All three clusters present greater connectivity values in the second MEG recording. A significant positive correlation was found between the connectivity values at the second MEG recording and p‐tau231 in the left precuneus. The same positive trend was found for right precuneus and left anterior cingulate.

Conclusion

To our knowledge, this is the first longitudinal study performed on cognitively unimpaired subjects, addressing connectivity changes and studying the relationship between those values and plasma biomarkers. The precuneus is one of the areas that accumulates early damage due to the pathology of AD. We believe that the hyperconnectivity found in both precuneus can be considered an early biomarker of AD risk, and the correlation with p‐tau231 levels support its pathological nature.
A Study of the Usefulness of Self‐Assessment Memory Scale (SAMS) for the Elderly in the Community
Authors: Kowa Hisatomo , Oki Yutaro , Imamura Miki , Suzuki Yuka
Published: December 2023

Background

It is very important to detect a slight cognitive decline and start therapies at the very early stage as soon as possible. We have established a new method named the Self‐Assessment Memory Scale (SAMS), consisting of 8‐picture recall and 16‐word recognition test. This study examined the usefulness and validity of SAMS in older adults participating in a dementia prevention (J‐MINT PRIME Tamba) study.

Method

The subjects were 97 older adults aged 65 year or older (24 men). The subject was administered a test consisting of an 8‐picture recall and a 16‐word recognition test on a tablet twice on separate days. The SAMS index was calculatedby adding up the ratio of correct responses to both tests (max point is two). The correlation with the WMS‐R logical memory II (LMII) score was examined.

Result

The mean and standard deviation of SAMS for the subjects in this study by age groups 65‐69, 70‐74, 75‐79 and 80‐ were 1.71 ± 0.24, 1.55 ± 0.25, 1.36 ± 0.29 and 1.36 ± 0.29, respectively. The first and second attempt of SAMS showed a significant correlation with the LMII score. (R = 0.56 and R = 0.63 respectively, both showed p<0.001). Comparing the first and the second score, the latter had better for more than 90% of the participants.

Conclusion

SAMS showed the good correlation with LMII in older people in this community‐based study. The result that the second score of the SAMS was better and correlated better with the LMII compared to the first one suggests that it is important to provide some trial opportunities for this test administered on a tablet in order to accurately assess cognitive function in elderly subjects.
Aged mice lacking interaction between FKBP51 and Hsp90 have normal cognition and memory
Authors: Zhao Zhe , Sun Xuelian , Wang Lisha , Wojcieszak Jakub , Winblad Bengt , Pavlov Pavel F.
Published: December 2023

Background

FK506‐binding protein 51 kDa (FKBP51) is a heat shock protein 90 (Hsp90) associated co‐chaperone that has recently emerged as a possible AD therapeutic target. Increased expression of FKBP51 was found in brains of aged mice and AD patients and overexpression of FKBP51 in mice impairs cognitive function in vivo. Role of HSP90‐FKBP51 complex in cognition and memory remains to be characterized.

Methods

• Using CRISPR/Cas9‐mediated genome engineering we have created a new mouse strain (Fkbp5TPRmut) harboring point mutations disrupting FKBP51 binding to Hsp90.

• Genotype of mice was confirmed using PCR‐based assay.

• Behavior of adult was assessed at 12 months of age using a battery of tests, including open field, novel object recognition, Y‐maze, and fear conditioning.

Results

• Mutation of FKBP51 leads to reduced interaction with Hsp90.

• Mutation of FKBP51 is stable and inherited in Mendelian‐like manner. Mutant homozygotes, heterozygotes and wild type mice can be clearly distinguished.

• Fkbp5TPRmut mice do not suffer from any health or fertility issues.

• At 12 months of age Fkbp5TPRmut mice do not display any impairment in behavior, cognition or memory.

Conclusion

• Two‐point mutation of FKBP51 render it incapable of interacting with Hsp90.

• Fkbp5TPRmut mice do not display harmful phenotype, allowing for a broad use of this model.

Further research is granted to reveal functional significance of FKBP51‐Hsp90 interactions, especially in Alzheimer’s disease or stress‐related disorders.
First genome‐wide association study on Alzheimer’s disease in the Argentinian and the Chilean populations
Authors: Dalmasso Maria Carolina , de Rojas Itziar , Olivar Natividad , Muchnik Carolina , Angel Bárbara , Gogler Sergio , Sanchez‐Avalos Mariana S , Chacon Maria Victoria , Aránguiz Rafael , Orellana Paulina , Cuesta Carolina , Galeano Pablo , Campanelli Lorenzo , Novack Gisella V , Medel Nancy , Lisso Julieta , Sevillano Zulma , Irureta Nicolas , Castaño Eduardo M , Montrreal Laura , Heilmann‐Heimbach Stefanie , Mintz Ines , Villella Ivana , Lambert Jean‐Charles , Solis Patricia , Politis Daniel , Mangone Carlos A , Gonzalez‐Billault Christian , Boada Mercè , Tárraga Lluís , Slachevsky Andrea , Albala Cecilia , Fuentes Patricio , Kochen Silvia , Brusco Luis Ignacio , Ruiz Agustin , Morelli Laura , Ramirez Alfredo
Published: December 2023

Background

Genome‐wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities.

Method

We performed a GWAS on sporadic Alzheimer’s disease (AD) including 540 patients and 852 controls from Argentina and Chile. We explored the variants associated with AD in European GWAS from European Alzheimer’s and Dementia Biobank (EADB), and tested their genetic risk score (GRS) performance in this admixed population.

Result

We detected APOE4 as single genome‐wide significant signal (OR = 2.93[2.37‐3.63], p = 2.6×10−23), and fifteen additional suggestive signals previously undetected. Nine of the 83 variants reported by EADB in Europeans were replicated, and the AD‐GRS presented similar performance in this Latin population, despite the score diminishes when the Native American ancestry rises.

Conclusion

We report the first GWAS on AD in a population from South America. It shows shared genetics that modulate AD risk between the European and the Latin American populations.
Identifying the optimal age to intervene in Alzheimer’s disease prevention trials: Validation of Emax modelling in sporadic Alzheimer’s disease
Authors: Baksh Asaad , Hithersay Rosalyn , Ritchie Karen , Carter Ben , Strydom Andre
Published: December 2023

Background

Many clinical trials of disease‐modifying therapies which seek to delay or prevent Alzheimer’s disease (AD) currently exist. However, a limitation of these trials is the absence of considering the earliest age groups at which decline in cognition can be detected to guide optimal participant recruitment.

Previous work has shown that in people with Down syndrome, Emax modelling can be used to identify the trajectory of cognitive decline in the preclinical and prodromal stages of AD. We aimed to validate Emaxmodelling to identify the earliest age of change in cognition in people who developed sporadic AD and compare these individuals to healthy controls without AD.

Method

Our sample consisted of participants aged 65 years old from the Enquête Sante ́ Psychologique – Risques, Incidence et Traitement (ESPRIT) study. Participants were categorised into two groups based on whether they were ever diagnosed with possible and probable AD while enrolled in the study (n = 101) or did not receive a diagnosis of any subtype of dementia (n = 1392, our healthy control group). We included measures of general cognitive functioning (Mini Mental State Examination; MMSE), verbal fluency, visual memory (Benton Visual Retention Test) and executive functioning (Trail Making Test).

Result

In people with AD, the earliest decline in general cognitive functioning could be detected in the 67‐71 age band while verbal fluency appears to decline from the 41‐45 age band and visual memory in the 82‐86 age band according to our model. In healthy controls, general cognitive functioning shows early change in the 87‐91 age band while verbal fluency starts to decline in the 43‐47 age band and executive functioning in the 85‐89 age band. Models for Trail Making Models for people with AD and visual memory for controls were not well fitted to the data.

Conclusion

We have shown that sensitivity to change depend on the primary outcome so authors designing trials need to ensure the research question, population and primary outcome are consistent. This has implications particularly for trials targeting the stages of disease before dementia diagnosis.
Poor cognition is associated with increased abundance of Alistipes and decreased abundance of Clostridium genera in the gut
Authors: Muhammad Jazmyn A , Ngouongo Yannick Joel Wadop , Ramirez Sophia , Kautz Tiffany F , Satizabal Claudia L. , Himali Jayandra Jung , Seshadri Sudha , Fongang Bernard
Published: December 2023

Background

Brain and gut health are intricately connected via the gut‐microbiota‐brain axis. Studies have shown that gut dysbiosis is associated with neurodegenerative diseases, including Alzheimer’s disease. However, how cognitive changes affects the gut microbiome structure is currently understudied. We aimed to assess the association between the gut microbiome and global cognitive scores in the Framingham Heart Study (FHS).

Method

Our sample included 1,014 participants (mean age 52, 55% female) of the third generation FHS cohort with available stool samples, cognitive assessments, and no history of dementia or stroke (Table 1). We quantified the gut microbiome composition using 16S rRNA sequencing and performed multivariable association and differential abundance analyses, adjusting for age, sex, education, BMI, and other confounders. The global cognitive score (GCS) was built using neuropsychological assessments of four cognitive domains: Executive function (trails‐making B); Processing speed (visual reproduction immediate and delayed); Language (similarity test); and Memory (logical memory immediate and delayed). Participants were additionally stratified by GCS with lower and higher scores indicating poor and normal cognition, respectively.

Result

Our results (Figure 1) showed that individuals with poor cognition have a decreased abundance of genera Clostridium (OR = 0.69, 95% CI [0.55, 0.86]) and Ruminococcus (0.93, [0.93, 0.94]). Meanwhile, the genus Alistipes, previously connected to anxiety, chronic fatigue syndrome, depression, and hypertension, was more abundant (1.06, [1.05, 1.06]) in the poor cognition group. Moreover, the genus Pseudobutyrivibrio, a butyrate‐producing bacteria from the rumen, was also found to be highly abundant (1.12, [1.11, 1.14]) in the poor cognition compared to normal. Finally, there was no difference in alpha and beta diversity between cognitive groups (Figure 2).

Conclusion

Our study suggests that the abundance of several genera, including Pseudobutyrivibrio, Alistipes, Ruminococcus, and Clostridium is associated with cognition in middle‐age. Clostridium was previously proposed as novel probiotics for human health, and increasing its abundance was viewed as an effective strategy to regulate and maintain the homeostasis of the gut microbiota. As all these bacteria have neuroprotective effects, manipulating their abundance through diet and pre/pro‐biotics could be a research path for preserving global cognitive function in the future.
Nutritional intake and adherence to dietary recommendation for patients with prodromal Alzheimers disease within a multimodal lifestyle trial
Authors: Levak Nicholas , Lehtisalo Jenni , Thunborg Charlotta , Westman Eric , Sindi Shireen , Rosenberg Anna , Andersen Pia , Andrieu Sandrine , Broersen Laus M. , Coley Nicola , Irving Gerd Faxén , Mangialasche Francesca , Pantel Johannes , Ngandu Tiia , Soininen Hilkka , Hartmann Tobias , Solomon Alina , Kivipelto Miia
Published: December 2023

Background

Multimodal lifestyle interventions have proven successful with at‐risk populations; however, little is known of the interventions effect on patients with prodromal Alzheimer’s disease. Even less is known of feasibility and adherence to dietary recommendations within the population.

Method

A 6‐month pilot trial was conducted with 93 participants randomized into three intervention arms. Two groups received physical exercise, cognitive training, nutritional guidance, monitoring and management of vascular and metabolic risk factors, and social stimulation, with one group receiving a medical food product. The third group was a self‐guided control group. Intake of individual macro‐ and micronutrients were analyzed from 3‐day food records. Adherence to recommendations assessed from food frequency questionnaires and by using a healthy diet index.

Result

For macro‐ and micronutrient intake there were no differences at the end of the intervention and intake was in line with other national food surveys. The group who received intervention and medical food product has significantly better healthy diet index score compared to the other groups.

Conclusion

There were few longitudinal significant differences on macro‐ and micronutrient intake, however, dietary intake improved significantly in itself when the intervention was complemented with a medical food product.
Structural Brain Correlates of Physical Activity in Offspring of Parents with and without Exceptional Longevity
Authors: Delpratt Natalie A , Barzilai Nir , Milman Sofiya , Verghese Joe , Blumen Helena M
Published: December 2023

Background

Previous studies suggest that frequent participation in physical activities (PA) promotes healthy aging by decreasing late‐life morbidity. Several studies further suggest that the volume of the prefrontal cortex and the hippocampus increases in response to PA. Brain volume is also preserved among offspring of those with exceptional longevity. This research examined associations between self‐reported PA and gray matter volume in older adults without dementia, and as function of parental longevity.

Methods

Self‐reported PA (activity level (low/high); activity rating (low/high); city blocks walked (<10/≥10); weekly aerobic exercise (<4/≥4); flights of stairs (≤5/>5); longest continuous walk (<4/≥4) and structural MRI data from 107 Ashkenazi Jewish older adults (79.08±6.52 years; 57.94% women) was examined. 59.81% of participants were offspring of parents with exceptional longevity (at least one parent lived 95 years or more) and 40.19% were offspring of parents with usual survival (both parents lived less than 95 years). Voxel‐based morphometry and multivariate covariance‐based analyses – adjusted for age, sex, years of education, and total intracranial volume – were used to identify gray matter patterns associated with PA. Linear regression was used to determine if these patterns varied as a function of parental longevity.

Results

Significant gray matter covariance patterns associated with PA ratings (p = 0.001) and flight of stairs (p = 0.004) were derived. The gray matter pattern associated with flight of stairs were primarily composed of middle cingulate, thalamus, superior frontal gyrus and insula. The gray matter pattern associated with PA level were primarily composed of caudate nucleus, insula, and hippocampus. None of the derived gray matter patterns varied as a function of parental longevity. No significant patterns were observed for city blocks walked, weekly exercise, or longest continuous walk.

Conclusion

Our results suggest that self‐reported PA – when assessed with activity rating and flight of stairs climbed – are associated with gray matter volume pattern composed of hippocampal, cingulate, insular, and prefrontal regions. Our results further demonstrated that these gray matter patterns do not vary as a function of parental longevity. Participating in PA may benefit the aging brain to a similar extent in offspring of parents with and without exceptional longevity.
Association of self‐reported and objective sleep parameters with hippocampus and white matter hyperintensities volumes in a community‐dwelling older adults
Authors: Cavaillès Clémence , Carriere Isabelle , Jaussent Isabelle , Dauvilliers Yves
Published: December 2023

Background

Numerous studies report that sleep disturbances are associated with brain alterations; yet, results still remain controversial. Our aim was thus to examine the associations between self‐reported and objective sleep parameters, and volumes of hippocampus and white matter hyperintensities (WMH).

Method

This cross‐sectional analysis used data from the French ESPRIT study. At baseline, 718 participants aged 65‐80 underwent a brain magnetic resonance imaging examination. Among them, 675 had hippocampus volume data and 712 had WMH volume data. They also completed a sleep questionnaire at baseline and 167 participants underwent an ambulatory polysomnography to assess their objective sleep. Logistic regression models were performed and minimally adjusted for age, sex, educational level, and APOE ε4 status to assess the associations between sleep parameters and volumes of hippocampus and WMH.

Result

The participants’ mean age at baseline was 71.4 years (±4.0) and 51.3% were women. We found that a short (≤6 hours) but also a long (≥9 hours) 24‐hour sleep duration, a late (>8 am) get‐up time and a low score at the Epworth Severity Scale were associated with a low hippocampal volume. However, these associations did not remain significant after false discovery rate (FDR) correction. We also observed, even after FDR correction, that an early get‐up time (≤6 am) and having difficulty in initiating sleep were associated with a high WMH volume whereas a late bedtime (≥11 pm) was associated with a low WMH volume. Regarding objective data, longer rapid eye movement sleep and slow wave sleep durations were associated with a low WMH volume, and a higher number of periodic leg movements during sleep was associated with a high WMH volume; but these associations were not significant after FDR correction. All the results remained similar after taking into account intracranial volume.

Conclusion

In this population‐based study in older adults, the most robust findings concerned higher WMH volume for participants with early get‐up time, difficulties in initiating sleep or late bedtime. Overall, these results are consistent with the general view that there may be specific types of sleep parameters that can play a role in brain alterations.
Health care service use in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) during an extended follow‐up period
Authors: Ngandu Tiia , Kulmala Jenni , Lehtisalo Jenni , Nurhonen Markku , Peltonen Markku , Mangialasche Francesca , Laatikainen Tiina , Strandberg Timo , Antikainen Riitta , Tuomilehto Jaakko , Soininen Hilkka , Kivipelto Miia ,   FINGER study group
Published: December 2023

Background

Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a randomized trial aiming to prevent cognitive decline with a 2‐year multidomain lifestyle intervention. Beneficial effects were detected not only in cognition, but also for co‐morbidity, as reported earlier. Aim of this work was to investigate, if the multidomain intervention also had an impact on the health care use and to evaluate possible cost‐effectiveness of the interventions in terms of health care costs.

Method

The FINGER trial recruited a population‐based cohort of 1259 at‐risk individuals aged 60‐77 living in six areas of Finland. They were randomized into a multidomain lifestyle intervention consisting of diet, exercise, cognitive training and vascular risk management (n = 631) or a regular health advice (control) (n = 628) group for two years and followed on average for 8 years. Health care use was obtained from nationwide registers where all primary and specialized care visits are recorded. We calculated days spent in hospital, ambulatory visits, outpatient visits in hospitals and primary care, and home care. Costs will be evaluated based on national reference prices.

Result

Altogether 99% of the population used some health care services and 66% were hospitalized at least for one day during the 8 years. 128 (10%) participants died during the follow‐up. Preliminary data indicated that the intervention group spent less days in the hospital, but there were no differences in outpatient visits. Further analyses are ongoing to evaluate the costs related to these visits.

Conclusion

Multidomain lifestyle intervention which is effective in prevention of cognitive decline can also help in reducing health care use at least in terms of hospital stays.
miRNAs in Cerebrospinal Fluid Associated with Alzheimer’s Disease: a Systematic Review and Pathway Analysis
Authors: Pereira Jessica Diniz , Teixeira Lívia Cristina Ribeiro , Caramelli Paulo , Veloso Adriano Alonso , da Conceição Izabela Mamede Costa Andrade , Luizon Marcelo Rizzatti , Borges Karina Braga Gomes
Published: December 2023

Background

Approximately 55 million people live with dementia, and 10 million cases are diagnosed each year worldwide (1). Alzheimer’s disease (AD) is the most common type of dementia and accounts for 60% ‐ 70% of reported cases (1). MicroRNAs are small non‐coding RNAs that present highly conserved sequences, involved in gene modulation and several molecular mechanisms (2). The miRNAs can be found in cerebrospinal fluid (CSF) and they are potential biomarkers for AD diagnosis (3). This study aimed to perform a systematic review about the expression of miRNAs in the CSF of AD patients compared to cognitive controls and carry out an analysis of the biological pathways regulated by these miRNAs

Method

A systematic literature search was performed in Medline/PubMed, the Cochrane Central Register of Controlled Trials, Scopus, Lilacs, Web of Science, Embase and gray literature, including observational studies that evaluated patients with AD and healthy individuals, which evaluated the miRNA expression in CSF. To verify the main signaling pathways regulated by the miRNAs, the software Gene Cards was used (table 1).

Result

2060 studies were retrieved and, after removing duplicates and reading titles, abstracts and full text, 26 studies met the inclusion criteria. We identified 171 differentially expressed miRNAs between AD and controls. Among them, the miRNAs ‐125b, ‐125‐5p, ‐138‐5p and ‐485‐5p presented differentiated expression between the groups commonly in these studies. The evaluation of signaling pathways showed that regulation of gene expression, cell proliferation, and gene silencing, are regulated by these miRNAs.

Conclusion

Our results suggest that the miRNAs ‐125b, ‐125‐5p, ‐138‐5p and ‐485‐5p are involved in AD‐related biological pathways and are potential CSF biomarkers to AD diagnosis.

1. DEMENTIA. World Health Organization, 2022. Available at: . Access at 21 jan. 2023.

2. CORREIA DE SOUSA, Marta et al. Deciphering miRNAs’ action through miRNA editing. International Journal of Molecular Sciences, v. 20, n. 24, p. 6249, 2019.

3. TAKOUSIS, Petros et al. Differential expression of microRNAs in Alzheimer’s disease brain, blood, and cerebrospinal fluid. Alzheimer’s & Dementia, v. 15, n. 11, p. 1468‐1477, 2019.
Safety profile of semaglutide in people aged 55 years and over: pooled data from the PIONEER, SUSTAIN and STEP phase 3 clinical programmes
Authors: Sabbagh Marwan , Boschini Cristina , Cohen Sharon , Fugger Magnus , Jessen Frank , Martino Gabriel Gerardo , Pedersen Sue D. , Tarazona Luis Rafael Solís , Aroda Vanita R.
Published: December 2023

Background

The risk of Alzheimer’s disease (AD) increases with age. The glucagon‐like peptide‐1 analogue semaglutide, approved for type 2 diabetes (T2D) and overweight/obesity, is being investigated in the phase 3 evoke and evoke+ trials in people with early AD aged 55‐85 years. There is a need to summarise semaglutide weight loss efficacy and safety data in older populations. We investigated the safety of semaglutide in people with T2D and/or overweight/obesity ≥55 years using data from the phase 3a PIONEER, SUSTAIN and STEP clinical programmes.

Method

Safety data for participants ≥55 years were pooled for: people with T2D receiving once‐daily oral semaglutide 3, 7 or 14 mg versus comparator (active or placebo) for 26‒78 weeks in PIONEER 1‒5 and 7‒10 (PIONEER pool, N = 4186); people with T2D receiving once‐weekly subcutaneous semaglutide 0.5 or 1 mg versus comparator (active or placebo) for 30‒56 weeks in SUSTAIN 1‒5 and SUSTAIN Japan (NCT02207374 and NCT02254291; SUSTAIN pool, N = 2825); and people with overweight/obesity (with/without T2D) receiving once‐weekly subcutaneous semaglutide 2.4 mg versus placebo for 68‒104 weeks in STEP 1‐6 (STEP pool, N = 1584).

Result

Data from 8595 participants were included. At baseline in the PIONEER, SUSTAIN and STEP pooled datasets, mean (standard deviation [SD]) age was 64.3 (6.4), 63.5 (6.1) and 62.0 (5.6) years, respectively, and mean (SD) body mass index was 30.8 (6.2), 31.0 (6.2) and 35.6 (6.2) kg/m2 (Table 1). The percentages of participants with adverse events (AEs) leading to treatment discontinuation in the semaglutide arms of PIONEER, SUSTAIN and STEP were 10.2, 9.1 and 7.7%, respectively, versus 5.2, 3.9 and 3.3% for the comparator arms (Table 2). Gastrointestinal disorders were the most frequently reported AE system organ class, with nausea, diarrhoea, constipation and vomiting the most frequent gastrointestinal AEs in the semaglutide arm of each pooled dataset (Table 2). Weight loss was greater with semaglutide versus comparator in all trials, with a tendency to plateau over time (Figure 1).

Conclusion

The safety profile of semaglutide in participants ≥55 years is similar to that observed in the overall population, supporting the evaluation of semaglutide in an older population with early AD in evoke.
Bio‐Hermes: A study to assess the relationship of blood and digital biomarkers with Aβ PET scans in older persons with normal cognition, MCI or mild AD
Authors: Beauregard Douglas W. , Mohs Richard , Dwyer John , Hollingshead Sarah , Smith Katy , Bork Jason , Kerwin Diana R.
Published: December 2023

Background

Recently developed blood and digital biomarkers may enable the identification of persons with amyloid deposits in the brain. While these biomarkers are promising, most haven’t been evaluated in populations like those screened for clinical treatment trials or in populations with racial and ethnic diversity similar to the US population. The Global Alzheimer’s Platform Foundation® (GAP) completed its biomarker study (Bio‐Hermes) comparing results of blood and digital biomarker tests with brain amyloid PET scans and traditional cognitive tests. The trial enrolled 1,002 participants in three cohorts: Cognitively Normal (CN), Mild Cognitive Impairment (MCI), and Mild AD.

Method

Within 18 months, 17 sites enrolled 1,002 participants (60‐85 y/o) in clinically defined cohorts of: CN (N = 417), MCI (N = 312), and Mild AD (N = 273). Traditional and digital cognitive testing, amyloid PET imaging, biospecimen collection, and speech analytics were performed. A subset of participants received a retinal exam. Blood biomarkers included, Aß 42/40, p‐Tau181/217/231, NfL, GFAP, full genome sequencing, including APOE status, and proteomics. Digital biomarkers included memory recall, executive functions, and drawing‐based and speech elicitation tasks. Blood biomarkers’ relationship to amyloid PET was measured using Spearman’s rank correlation. A ROC curve analysis will assess the sensitivity and specificity of each biomarker and combination of biomarkers compared with amyloid positivity from PET.

Result

Statistical models to be competed in April 2023 for presentation.

24% of participants were from underrepresented populations (URP) either African American, Hispanic or other. The CN cohort was 61% female, with 21% amyloid PET Positive; the MCI cohort was 54% female with 34% amyloid PET Positive; the Mild AD cohort was 51% female with 62% amyloid PET Positive. Penalized multiple regression will be used to predict amyloid level (continuous) and amyloid positivity status. Candidate predictors include cohorts, blood‐based biomarkers, cognitive assessments (rating scales and digital), retinal measurements, and speech recognition digital biomarkers.

Conclusion

Bio‐Hermes generated a unique, well‐characterized, diverse sample set that determined the utility of several promising biomarkers. Validation of these biomarkers will expedite AD clinical trial enrollment by quickly identifying appropriate participants while reducing the variability and burden of screen failures from high‐cost brain scan procedures.