bluuebunny/crossref_metadata_2025_split huggingface dataset:
Midlife insulin resistance, APOE genotype, and change in late‐life brain amyloid accumulation – a 5‐year follow‐up 11C‐PIB‐PET study
Authors: Pietilä Elina M. , Ekblad Laura L. , Snellman Anniina , Toppala Sini , Tuisku Jouni , Helin Semi , Viitanen Matti , Jula Antti , Rinne Juha O. 
Published: June 2023

AbstractBackgroundMidlife insulin resistance has been associated with an increased risk for cognitive decline (1) and amyloid accumulation (2). We hypothesized that midlife insulin resistance would predict amyloid accumulation 20 years later, and the change in brain amyloid accumulation during the 5‐year imaging follow‐up.MethodsWe studied 60 cognitively normal participants from the Finnish population‐based Health2000 study in 2014‐2016 with 11C‐PIB‐PET (2). They were recruited according to their homeostatic model assessment of insulin resistance (HOMA‐IR) values measured 15 years earlier in 2000, and their APOEε4 genotype. The insulin resistance group (IR+, HOMA‐IR <1.25) and the control group (IR−, HOMA‐IR > 2.17) both included 30 participants and 50% APOEε4 carriers. In 2019‐2021 43 participants took part in the 5‐year 11C‐PIB‐PET‐imaging follow‐up. Here, we report the change in amyloid accumulation in the IR+ group (n = 19, 57% APOE ε4 carriers) and the IR‐ group (n = 24, 46% APOEε4 carriers) during this 5‐year interval. 11C‐PIB‐PET images were analyzed with an in‐house pipeline and standard uptake value ratio (SUVR) composite scores were calculated. Kruskal‐Wallis test and the Steel‐Dwass method was used to analyze the difference in amyloid accumulation rates between groups, and Spearman’s correlation was utilized to assess the association between HOMA‐IR and amyloid accumulation.ResultAt the 20‐year follow‐up, amyloid accumulation was significantly higher in the IR+ group than the IR‐ group (composite SUVR 2.43 vs. 1.96, p = 0.03) (Fig. 1). The change in amyloid accumulation during 5 years was significantly higher in the IR+/APOEε4+ group than in either IR−/APOEε4− (mean change in composite SUVR 0.79 vs. 0.32, p = 0.02) or IR+/APOEε4− groups (mean change in composite SUVR 0.79 vs. 0.26, p = 0.046,) (Fig. 2). HOMA‐IR in 2000 (rS = 0.39, p = 0.01) and 2014‐2016 (rS = 0.34, p = 0.03), but not in 2019‐2021 (rS = 0.24, p = 0.13), correlated with 11C‐PIB composite SUVR at the 20‐year follow‐up.ConclusionThese results suggest that IR could be an additive risk factor for late‐life amyloid accumulation in APOEε4 carriers, and that midlife, but not late‐life IR associates with amyloid accumulation.1) Ekblad et al., Diabetes Care 20172) Ekblad et al., Neurology 2018
Interaction between APOE4 and lifestyle on neuroimaging biomarkers and cognition in cognitively unimpaired older adults
Authors: Felisatti Francesca , Chauveau Léa , de Flores Robin , Marchant Natalie L , Collette Fabienne , Demnitz‐King Harriet , Whitfield Tim , Requier Florence , Palix Cassandre , Haudry Sacha , Delarue Marion , la Sayette Vincent De , Vivien Denis , Poisnel Géraldine , Chetelat Gael , Gonneaud Julie 
Published: June 2023

AbstractBackgroundAPOE4 is the main genetic risk factor for Alzheimer’s disease (AD). Recent findings suggest that lifestyle factors could modulate the association between APOE4 and cognitive impairment and/or dementia risk. However, a comprehensive assessment of the interactions between lifestyle and APOE4 status on neuroimaging and cognitive markers of aging and AD is still missing. Our objective is to assess this question in cognitively normal elderly.MethodBaseline data of 134 cognitively unimpaired older adults (mean age: 69) from the Age‐Well study were analysed. They underwent lifestyle questionnaires (physical and cognitive activity, and diet), neuropsychological assessment (global cognition, memory, attention and executive functions) and multimodal neuroimaging (structural MRI, FDG‐ and Florbetapir‐PET). Interactions between lifestyle and APOE4 status on neuroimaging and cognition were assessed for each lifestyle factor separately.ResultThere was an interaction between APOE4 status and cognitive activity on neuroimaging measures (p‐values<.04), such that higher cognitive engagement was associated with lower grey matter volume in the parahippocampal cortex and lower brain perfusion in the entorhinal and perirhinal cortices in APOE4 carriers only (Figure 1A). However, greater cognitive engagement was associated with increased cognitive performance (global cognition, executive function and attention, all p‐values<.005), and this irrespective of APOE4 status (i.e., no cognitive activity x APOE4 status interaction; Figure 1B). For diet, interactions were evidenced (p‐values <.04) such that higher adherence to the Mediterranean diet was associated with i) higher brain glucose metabolism in the medial temporal lobe (Figure 2A) and ii) higher performance on attention tests (Figure 2B) in APOE4 carriers only. No interactions were found for physical activity.ConclusionOur results indicate that APOE4 carriers with higher cognitive activity had lower brain outcomes but preserved cognition, suggesting that enriched cognitive engagement promotes cognitive resilience in this population. On the other hand, APOE4 carriers with higher adherence to the Mediterranean diet had greater cerebral metabolism and greater attention capacities. Overall, this suggests that distinct lifestyle factors differentially help APOE4 carriers to resist or cope with brain alteration and postpone cognitive decline.ClinicalTrials.gov Identifier: NCT02977819.
Sleep, physical activity, sedentary behavior, and risk of incident dementia: A prospective cohort study of 431,924 UK Biobank participants
Authors: Huang Shu‐Yi , Yu Jin‐Tai 
Published: June 2023

AbstractBackgroundSleep, physical activity (PA), and sedentary behavior have been individually associated with the risk of dementia, but findings are inconsistent. Their joint associations with dementia also remain unknown. We aimed to investigate the independent and joint associations of sleep duration, PA, and sedentary behavior with dementia risks and the underlying mechanisms.MethodA total of 431,924 participants with a median follow‐up 9.0 years from UK Biobank without dementia were included. Cox proportional hazards regression was performed to test the independent and joint association of sleep, PA, and screen‐based sedentary behavior with dementia. We also test the non‐linearity of these associations. Non‐linear regression was performed to examine the associations of each behavior with brain morphometric measures.ResultDuring a median observation follow‐up period of 9.0 years, 5390 participants developed an incident dementia among 431,924 individuals. Sleep duration, leisure‐time PA, and screen‐based sedentary behavior individually associated with dementia risks in different non‐linear association modes. Sleep duration associated with dementia risk in a U‐shape, and participants with a seven‐hour sleeping pattern showed the lowest dementia risk. Leisure‐time PA associated with dementia in a curvilinear relationship with diminishing returns, and sedentary behavior associated with dementia in a J‐shaped association. The dementia risk was 17% lower in the high leisure‐time PA group ((95%CIs), 0.83 (0.76‐0.91)) and 22% higher in the high sedentary behavior group (1.22 (1.10‐1.35)). A combination of seven‐hour sleep, moderate‐to‐high leisure‐time PA, and low‐to‐moderate sedentary behavior showed lower dementia risks (0.66 (0.56‐0.78)) compared to the referent group with atypical sleep, low leisure‐time PA, and high sedentary behavior. Notably, each of the three behaviors was non‐linearly associated with brain morphometric measures in the similar modes as their associations with dementia. Proper intensity/time‐spent on each behavior of interest was associated with higher brain volumes. The relationship of each behavior with dementia was partially mediated by cerebrovascular diseases.ConclusionA 7‐hour/day sleep duration, higher leisure‐time PA, and lower sedentary behavior are independently and jointly associated with lower dementia risks. Our findings underscore the potential of changing these three daily behaviors concomitantly to mitigate dementia risks in population‐wide strategies.
The burden of COVID‐19 on all‐cause mortality in older adults living in Wales
Authors: Lai Helen , Kolanko Magdalena A , North Laura , Akbari Ashley , Tzoulaki Ioanna , Sharp David J , Soreq Eyal 
Published: June 2023

AbstractBackgroundThe COVID‐19 pandemic has profoundly impacted the lives of people living with dementia (PLWD). Mitigating measures have led to extreme social isolation and reduced or limited capacity within routine health and social care services. Using anonymised individual‐level, population‐scale linked electronic healthcare, demographic and mortality records in Wales, we have examined the impact of the COVID‐19 pandemic on all‐cause mortality in PLWD and in older adults living with other comorbid conditions.MethodUsing the Secure Anonymised Information Linkage (SAIL) Databank (Lyons et al., 2009), we identified six cohorts of individuals aged 50‐101 and living in Wales on or before 1st February 2020, with conditions in the following domains: dementia, cardiovascular, respiratory, metabolic, renal, and cerebrovascular. For each, we identified paired samples matched by age and sex using propensity sampling. Evidence for comorbidities were extracted using ICD‐10 and READ codes. We quantified excess mortality in PLWD during the COVID‐19 period (July 2020 – May 2021 at the point of the analysis) by comparing weekly mortality to a baseline rate (2015‐2019 average) and to the population paired sample. We then extracted retrospective datasets across sixteen‐month periods from 2010‐2020. Finally, we estimated all‐cause mortality odds‐ratios for each period and comorbid domain using logistic regression, controlling for age and sex.ResultPLWD had higher risk of all‐cause mortality compared to a matched sample of individuals without dementia (Figure 1a), especially during the first wave of the pandemic (April 2020, Figure 1b), and in older PLWD (Figure 1c). Examining evidence across other comorbid conditions (Figure 2), logistic regression modelling showed the greatest increase in mortality odds among PLWD (Figure 2f) compared to people without dementia, increasing from 4.47 in 2018 to 5.61 in 2020. The magnitude of the increase in odds among people with cardiovascular, metabolic, renal, and cerebrovascular conditions from 2020‐2021 compared to previous years was smaller compared to the increase in PLWD (Figures 2a, 2c‐e).ConclusionPLWD experienced increased mortality risk compared to those living with other comorbid conditions during 2020. Further work will focus on the composition of death causes and the contribution of other comorbidities to all‐cause mortality among PLWD.
Brain neural synchronization mechanisms are affected by aging in cognitively unimpaired seniors and patients with Alzheimer’s disease and mild cognitive impairment
Authors: Percio Claudio Del , Lizio Roberta , Noce Giuseppe , Lopez Susanna , Soricelli Andrea , Ferri Raffaele , Tucci Federico , Güntekin Bahar , Yener Görsev , Frisoni Giovanni B , Babiloni Claudio 
Published: June 2023

AbstractBackgroundThe resting state eyes‐closed electroencephalographic (rsEEG) alpha (8‐12 Hz) rhythms reflect cortical neural synchronization mechanisms underpinning the inhibition of sensory, cognitive, and motor areas in parietal, temporal, and occipital cortex during a condition of low vigilance. Here we tested the hypothesis that age may diversely affect rsEEG alpha (8‐12 Hz) rhythms recorded in normal elderly (Nold) seniors and patients with Alzheimer’s disease and mild cognitive impairment (ADMCI).MethodClinical, magnetic resonance imaging (MRI) and rsEEG datasets in 63 ADMCI and 60 Nold individuals were taken from an international archive. The rsEEG rhythms were investigated at individual delta, theta, and alpha frequency bands as well as fixed beta (14‐30 Hz) and gamma (30‐40 Hz) bands. Each group was stratified into three subgroups based on age ranges (i.e., tertiles).ResultAs compared to the younger Nold subgroups, the older one showed greater reductions in the rsEEG alpha rhythms with major topographical effects in posterior regions (Figure 1). On the contrary, in relation to the younger ADMCI subgroups, the older one displayed lesser reduction in those rhythms (Figure 1). Furthermore, a decrease in the total grey matter (GM) volume and total cortical thickness as well as an increase in the white matter (WM) hypointensity were found in the older ADMCI subgroups compared to the younger ADMCI subgroups (Figure 2).ConclusionThe results of the present study suggest that in Nold seniors, the aging factor may significantly affect neurophysiological brain neural synchronization mechanisms underpinning the generation of dominant rsEEG alpha rhythms. In contrast, rsEEG alpha rhythms in ADMCI patients may be more affected by the disease variants, with more deleterious effects observed in early‐ than the late‐onset ADMCI patients. In the ADMCI patients, the mere effects of the aging factor may be hidden by dysfunctions in subcortical structures, including the cholinergic basal forebrain and thalamus.
Decreased activities of prefrontal and temporal lobes in patients with mild cognitive impairment and mild Alzheimer’s disease on a clock drawing task via functional near‐infrared spectroscopy imaging
Authors: Zhong Fuxin , Zhang Wenbo , Lü Yang 
Published: June 2023

AbstractBackgroundStudies have shown that changes in cerebral blood flow occur in the early stage of dementia, including Alzheimer’s disease (AD), and decreased cerebral blood flow contributes to impairment of brain activities, then affects cognitive function. To diagnose AD in very early stage, such as mild cognitive impairment (MCI), it is therefore necessary to find a new way to detect early activities of brain, such as functional near‐infrared spectroscopy (fNIRS).MethodsThe clock drawing task (CLOX) is one of the widely used neurocognitive function scoring test for dementia. In this study, brain activities were examined in patients with MCI (n = 8) and mild AD (n = 8) during an unprompted CLOX drawing using functional near‐infrared spectroscopy (fNIRS). The concentration changes of oxyhemoglobin (HbO), reflecting brain activities indirectly, were tested in each group via fNIRS.ResultsActivation in the right hemisphere was significantly attenuated in mild AD compared with MCI. With the development of disease severity from MCI to mild AD, the reductions of HbO2 concentrations in the right prefrontal and right temporal lobe were observed greater and steeper. The HbO2 in mild AD was significantly lower than that in MCI (false discovery rate corrected, p <0.025). In addition, HbO2 concentration was positively associated with the clinical score of MMSE (MCI group, p<0.05; mild AD group, p<0.05).ConclusionThis study suggests that activity in the frontal and temporal lobes of mild AD is reduced compared to MCI. Those results reflects that CLOX is an effective tool for extracting fNIRS signal features. In addition, fNIRS‐based analysis has great promise for exploring the mechanisms of changes in the sensory‐spatial function of MCI and mild AD.
The impact of dance‐movement interventions on psychological health in older adults: A systematic review and meta‐analysis of randomized controlled trials
Authors: Zarucha Alexis , Podolski Odile Sophie , Schaaf Leah , Cassing Vilana , Whitfield Tim , Wirth Miranka 
Published: June 2023

AbstractBackgroundGood psychological health is proposed as a key factor in the protection against Alzheimer’s disease (AD) and age‐related cognitive decline1. Multimodal motor, cognitive, sensory, and social enrichment as induced by dance‐movement interventions (DMI) could promote psychological health in the older population. This systematic review and meta‐analysis investigated the impact of DMI compared to control intervention (active/passive) on psychological health in older adults.MethodsA systematic search of three databases (PubMed, Web of Science, PsycInfo; screenings: April and November 2021) was conducted following PRISMA guidelines. Criteria included randomized controlled trials (RCTs) evaluating the effects of DMI (minimum 4 weeks’ duration) on health‐related psychological outcomes (primary outcome) and global cognitive functioning (secondary outcome) among non‐demented older adults (≥ 55 years of age). A random‐effects meta‐analysis with robust variance estimation was carried out. This review was registered with PROSPERO (CRD42021265112).ResultsData of 13 eligible primary RCTs (n = 943, n‐DMI = 474, n‐control = 469) were synthesized. Overall heterogeneity of results and risk of bias across RCTs were high. DMI had a small positive impact on psychological health compared to control (g = 0.31; 95% Confidence Interval (CI): [0.09, 0.53]; p = .01, I2 = 62.55). Separation of psychological health into positive and negative outcomes and particularly social and emotional aspects showed similar trends favouring DMI compared to control (see Figure 1). Analysis of secondary outcomes indicated a positive effect of DMI on global cognitive functioning (g = 0.48; 95%CI: [0.03, 0.93], p = .04, I2 = 82.44). Exploratory subgroup analyses suggested that the implementation of longer intervention durations and psychotherapeutic elements increase the psychological health benefits of DMI.ConclusionMultimodal interventions, as specifically offered by DMI, may serve as an effective tool to promote psychological health together with cognitive functioning in older adults. High‐quality future trials are needed to expand evidence on the particular aspects of psychological health and identify underlying neurophysiological correlates. We will present a protocol for a prospective RCT to assess the impact of a DMI on psychological, cognitive and brain health outcomes in the older population at increased risk of AD.References1Livingston G, et al. Lancet 2020.
Cross‐sectional and longitudinal associations of plasma makers of amyloid and tau pathology and neurodegeneration with gait speed
Authors: Syrjanen Jeremy A. , Vemuri Prashanthi , Graff‐Radford Jonathan , Machulda Mary M. , Knopman David S. , Petersen Clifford R. JackRonald C. , Mielke Michelle M. 
Published: June 2023

AbstractBackgroundHigher brain amyloid PET is associated with slower gait speed and has been hypothesized to play a role in age‐related mobility decline. With the development of blood‐based biomarkers of Alzheimer’s disease pathology, we examined whether plasma levels of amyloid‐beta (Aβ)40, Aβ42, the Aβ42/Aβ40 ratio, phosphorylated tau 181 (p‐tau181) and 217 (p‐tau217), total tau, and neurofilament light chain (NfL) were associated with gait speed.MethodThis study included 779 cognitively unimpaired participants (median age 75, 54.8% male, median follow‐up 6.8 years) in the Mayo Clinic Study of Aging with concurrent measurement of plasma biomarkers and gait speed. Individuals with chronic kidney disease or a history of stroke were excluded. The plasma markers (pg/mL) were measured on the Quanterix Simoa® HD‐1 analyzer (total tau, Aβ42, Aβ40, NfL) and the Meso Scale Discovery platform (p‐tau181, p‐tau217). Gait speed (m/s) was obtained by timing a self‐paced walk across 25 ft using a stopwatch. Linear mixed effects models, with subject‐specific intercepts and slopes for time since baseline, with z‐scored baseline plasma markers were used to predict cross‐sectional and longitudinal gait speed. All models adjusted for baseline age and sex.ResultAt baseline, higher Aβ42 [Beta = ‐0.019; 95%CI = (‐0.035, ‐0.004)], total‐tau [‐0.026; (‐0.041, ‐0.011)], and p‐tau181 [‐0.021; (‐0.036, ‐0.006)] were associated with slower gait speed. Gait speed decreased, on average, by about 0.015 m/s annually for those in this study. Each one standard deviation (SD) increase in baseline level of plasma Aβ40 [‐0.005; (‐0.007, ‐0.002)], NfL [‐0.006; (‐0.009, ‐0.004)], and p‐tau217 [‐0.004; (‐0.007, ‐0.001)] accelerated this decline over time. In contrast, each one SD increase in Aβ42/Aβ40 ratio [0.003; (0.001, 0.006)] mitigated decline. Additional analyses adjusting for Charlson comorbidity index, Beck Depression Inventory, body mass index, and APOE E4 allele status gave similar results.ConclusionBoth cross‐sectional and longitudinal associations of plasma markers of amyloid and tau pathology and neurodegeneration with gait speed among cognitively unimpaired individuals were present. Therefore, not only are these markers of cognitive changes, they are also related to motor changes such as those affecting gait speed.
Apolipoprotein C proteins in plasma non‐high‐density lipoprotein fractions and development of Alzheimer’s disease, central arterial stiffness, and cerebral small vessel disease in older adults
Authors: Glittenberg Matthew , Flaten Zachery , Kumar Sai Kaushik Shankar Ramesh , Li Danni 
Published: June 2023

AbstractBackgroundPlasma non‐high‐density lipoproteins impact development of central arterial stiffness and cerebral small vessel disease (cSVD), significantly contributing to Alzheimer’s disease (AD) and related dementias (ADRDs) through an increase in cerebral amyloid beta (Aβ) burden and acceleration of atrophy in susceptible brain regions. We sought to identify proteins in three non‐HDL plasma lipoproteins (very‐low density lipoprotein [VLDL], intermediate‐density lipoprotein [IDL], low‐density lipoprotein [LDL]) and their cross‐sectional associations with brain amyloid deposition, central arterial stiffness, neuroimaging features of cSVD (e.g., white matter hyperintensity volume), brain volumes susceptible to AD and cSVD, and incidence of dementia.MethodPlasma samples from 66 participants of the Atherosclerosis Risk in Communities (ARIC) study were fractionated to isolate VLDL, IDL, and LDL and analyzed using label‐free liquid chromatography‐mass spectrometry (LC‐MS) with Data‐Independent Acquisition. Acquired MS spectra were processed using Spectronaut™ to give protein identification and relative protein abundances were calculated using R. Linear regression models were used to examine the cross‐sectional associations between protein abundances in VLDL, IDL or LDL and brain amyloid deposition (measured by amyloid PET scan), white matter hyperintensities (WMH) volume (measured by brain MRI), central arterial stiffness (carotid‐femoral and heart‐femoral pulse wave velocity), AD‐signature region, frontal, parietal, and hippocampal brain region volumes (measured by brain MRI), and incidence of dementia. Regression models were adjusted for age, sex, race, number of APOε4 alleles, and cholesterol level (if applicable). Additionally, differential analysis (student’s t‐test) was used to compare protein abundances in non‐HDL lipoproteins between participants with elevated versus normal brain amyloid deposition.ResultWe identified 50, 78, 81 proteins in VLDL, IDL, and LDL, respectively. The most significant findings were: 1) higher levels of apolipoprotein C proteins in VLDL, IDL, and LDL were associated with lower WMH volume or less central arterial stiffness; 2) lower levels of apolipoprotein C proteins in VLDL, IDL, and LDL were associated with less incidence of dementia; 3) lower levels of apolipoprotein C proteins in VLDL, IDL, and LDL for participants with elevated amyloid deposition.ConclusionThese results suggest the possible role of apolipoprotein C proteins present in non‐HDL‐lipoproteins in the development of AD, central arterial stiffness, and cSVD.