bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moderate to vigorous physical activity and sedentary time as predictors of cognitive function in older adults with hypertension: NHANES 2011‐2014
Authors: Hoffmann Coles M , Petrov Megan E 
Published: December 2021

AbstractBackgroundHypertension is associated with increased risk for cognitive decline. Lifestyle behaviors such as moderate to vigorous physical activity (MVPA) and sedentary time (ST) may mitigate this decline, though limited research on the joint association exists. The aim of the study was to examine the joint association of MVPA and ST on cognitive function by hypertension status.MethodsAdults (n=2916, ≥60yrs) from the 2011‐2014 National Health and Nutrition Examination Survey (NHANES) were assessed for their participation in MVPA (meets recommendations: ≥150min MPA and/or ≥75min MPA vs does not meet recommendations: <150min MPA and <75min VPA), self‐reported ST (≤7hrs ST vs >7hrs ST), hypertension, and cognitive function (Digit Symbol Substitution Test [DSST]; Animal Fluency [AF] test). Weighted linear regression analyses were conducted to assess joint association of MVPA and ST on cognitive function, and test the modifying effect of hypertension status (alpha level set at 0.1) after adjustment for demographics, cardiovascular disease, diabetes, body mass index (BMI), and depression.ResultsSee Table. There were significant main effects for combined MVPA and ST on DSST (Wald F(3,30)=3.393, p=.031) and AF (Wald F(3,30)=17.33, p<.001). Participants who did not meet MVPA recommendations regardless of ST had significantly worse scores on DSST compared to participants who met MVPA recommendations and reported ≤7hr ST. Participants who did not meet MVPA recommendations and had ≤7hr ST had significantly worse scores on AF. There was a significant interaction between MVPA‐ST groups and hypertension status on AF (Wald F(3,30)=3.766, p=.021), but not on DSST. Stratified analyses indicated among individuals without hypertension significance was maintained. For participants with hypertension, not meeting MVPA recommendations regardless of ST was associated with significantly worse scores.ConclusionsIn a sample of adults, meeting recommendations for MVPA was associated with better cognitive outcomes regardless of ST. Among individuals with hypertension regular MVPA regardless of ST was significantly associated with higher scores on one measure of executive function. This research highlights the added importance for individuals with hypertension to participate in the recommended amount of MVPA.
Quantitative assessment of cortical excitability in Alzheimer’s dementia and its association with clinical symptoms: A systematic review and meta‐analyses
Authors: Joseph Shaylyn , Patterson Rachel A. , Wang Wei , Blumberger Daniel M. , Rajji Tarek K. , Kumar Sanjeev 
Published: December 2021

AbstractBackgroundAlzheimer’s Disease (AD) is characterized by cognitive and neuropsychiatric symptoms (NPS). Studies using electroencephalography (EEG) have shown increased epileptiform and epileptic activity in AD. Transcranial magnetic stimulation (TMS) studies have also shown abnormal cortical excitability in AD, however findings have been inconsistent. Further, relationship between cortical excitability and clinical symptoms of AD is not clear. This review and meta‐analyses aims to synthesize the existing evidence for abnormal cortical excitability in AD and its relationship with clinical symptoms.MethodWe systematically searched and reviewed publications that quantitatively assessed cortical excitability, using TMS resting motor threshold (rMT), active motor threshold (aMT), motor evoked potential (MEP) or directly from the cortex using TMS‐EEG via TMS‐evoked potential (TEP). Effect sizes and 95% confidence intervals (CI) of rMT and aMT were calculated using Hedges’ g and meta‐analyzed using a random effects model. Heterogeneity among studies was assessed by Cochran’s Q and I2 statistic.ResultWe identified 895 publications out of which 68 were reviewed in full‐text and 37 were included in the final review. Thirty studies using rMT and seven using aMT were included in the meta‐analyses. The AD group had reduced rMT (Hedges’ g = ‐0.99, 95% CI [‐1.29, ‐0.68], p < 0.00001) and aMT (Hedges’ g = ‐0.87, 95% CI [‐1.50, ‐0.24], p < 0.00001) as compared with control groups, indicative of higher cortical excitability. Evidence of considerable heterogeneity was found across the studies (Q (29) = 85.68, p < 0.00001, I2 =81%). Qualitative review of the literature showed some evidence of increased MEP amplitude (n = 2 studies), however findings related to TEP were inconsistent. Further, there was some evidence (n = 4 studies) supporting an inverse association between cortical excitability and global cognition. No publications reported on the relationship between cortical excitability and neuropsychiatric symptoms (NPS).ConclusionThere is strong evidence of increased motor cortex excitability in AD and some evidence of an inverse association between excitability and cognition. Future studies should assess cortical excitability from non‐motor areas and examine its relationship with cognition and NPS.
Assessments of instrumental activities of daily living in low‐middle income countries: A systematic review
Authors: Ardle Ríona Mc , Yemm Heather , Goodon Michaela , Poole Marie , Narytnyk Alla , Dotchin Catherine , Paddick Stella‐Maria , Robinson Louise 
Published: December 2021

AbstractBackgroundDementia prevalence in low‐middle income countries (LMIC) is projected to rise exponentially by 2050. However, less than 10% of people with dementia have a formal diagnosis, partially due to difficulties in clinically recognizing and diagnosing dementia. Culturally‐appropriate screening tools for dementia are needed. As functional impairments are fundamental elements of dementia diagnosis, assessments of instrumental activities of daily living (IADLs) may be appropriate screening tools. IADLS are complex daily tasks required to maintain functional independence (e.g. managing finances). They are susceptible to cultural variation, such as differences in gender roles cultural responsibilities of older adults in LMICs (e.g. social‐orientated activities). IADL assessments validated in high‐income countries may not be appropriate for LMICs. The aim of this systematic review is to identify IADL assessments which have been developed, validated or adapted for use in LMICs, and report how accurate, valid and reliable these tools are for identifying dementia.Method2,507 articles were systematically reviewed during title and abstract screen. 46 full‐text articles were reviewed for inclusion, with 16 English‐language articles confirmed and 13 currently undergoing final adjudication.ResultsFrom the confirmed 16 articles, 10 LMIC countries are represented (Figure 1). 16 different IADL assessments were investigated; two studies compared two different IADL tools. Eight (50%) were existing tools translated from their original language into a target language (in Brazil (n=4), Turkey (n=2), Iran (n=1), Argentina (n=1)), three (19%) were existing scales culturally adapted and translated to a target language (Brazil (n=3)), and six (38%) were novel tools developed for specific cultures (in Tanzania (n=1), India (n=2), Thailand (n=1), Nigeria (n=1), Republic of Congo and Central African Republic (n=1)). Eight studies (50%) reported accuracy of tools to correctly identify dementia. Sensitivity ranged between 63‐97% and specificity between 69‐100%.ConclusionFrom preliminary trends, bespoke culturally‐specific tools are more likely to be investigated in African and South Asian countries, while translated Western tools are more likely to be investigated in South American and West Asian countries. It is currently unclear which approach is best, but further synthesis will lead to recommendations regarding future validation and adoption of valid, reliable IADL tools in LMICs.
Everyday functioning in a community‐based volunteer population: Factors associated with concordance between participant and study partner—Report
Authors: Verrijp Merike , Dubbelman Mark A. , Visser Leonie N.C. , Jutten Roos J. , Nijhuis Elke W , Van Hout Hein PJ , Scheltens Philip , van der Flier Wiesje M , Sikkes Sietske A.M. 
Published: December 2021

AbstractBackgroundWith the shift towards preclinical phases of Alzheimer’s disease (AD) and other neurodegenerative diseases in research studies and clinical trials, the question arises if participants can reliably self‐report their level of everyday functioning. Here, we aim to investigate the factors related to concordance between participant‐ and study partner‐report versions of the Amsterdam Instrumental Activities of Daily Living Questionnaire (A‐IADL‐Q) in a community‐based volunteer population.MethodCommunity based volunteers (participants) and their study partners were recruited from a Dutch brain research registry. IADL concordance between participant and study partner was investigated using intraclass correlation coefficient (ICC). Dyads were subsequently categorized as (1) concordant (<2 points differences in A‐IADL‐Q score); (2) discordant, with study partner reporting more difficulties (study partner>participant) and (3) discordant, participant>study partner. Multinomial logistic regression models were used to investigate the association between subjective cognitive decline, depressive symptoms (Geriatric Depression Scale‐5), type of relationship, objective cognitive functioning (Cognitive Online Self‐Test Amsterdam), and concordance as dependent variable.ResultA total of 1213 participants (18‐93 years of age, 68.3% female) and 1213 study partners (18‐88 years, 45.8% female) completed the A‐IADL‐Q. The majority of participants (52.8%) and study partners (59.5%) reported no IADL difficulties. Figure 1 shows the percentage of IADL difficulty reported for individual activities by both participants and study partners. Of the dyads, 653 (53.8%) were in concordance, with an ICC of .55 (95%CI=[.51, .59], Figure 2). Depressive symptoms and memory complaints increased the odds of participants reporting more IADL difficulties compared to their study partner (odds ratio (OR)=1.31, p<.01 and OR=2.56, p<.01, Table 1). An inverse association was found between A‐IADL‐Q and concordance, to the extent that higher A‐IADL‐Q scores were associated with a lower odds of study partner>participant discordance (OR=0.68, p<.01).ConclusionA slight majority of dyads showed concordance between participant‐ and study partner‐reported IADL scores. Our findings suggest that concordance is less likely in the presence of memory complaints, depressive symptoms and with lower levels of everyday functioning. These findings implicate that participant‐ and study partner report capture different aspects of functional decline, which might influence the study design of longitudinal aging studies.
Plasma biomarkers predict longitudinal amyloid accumulation, tau burden, brain atrophy and cognitive decline in early Alzheimer’s disease
Authors: Pereira Joana B. , Janelidze Shorena , Stomrud Erik , Palmqvist Sebastian , Dage Jeffrey L. , Mattsson‐Carlgren Niklas , Hansson Oskar 
Published: December 2021

AbstractBackgroundIt is currently unclear whether plasma biomarkers can be used as independent prognostic tools for early Alzheimer’s disease (AD). In this study we sought to address this question by assessing whether plasma biomarkers can predict changes in amyloid load, tau accumulation, brain atrophy and cognition in non‐demented individuals.MethodTo achieve this, plasma amyloid‐β 42/40 (Aβ42/40), phosphorylated‐tau181 (P‐tau181), phosphorylated‐tau217 (P‐tau217) and neurofilament light (NfL) were determined in 120 non‐demented individuals, 123 patients with AD dementia and 15 patients with a non‐AD dementia from the Swedish BioFINDER‐2 study, who underwent longitudinal amyloid (18F‐flutemetamol) and tau (18F‐RO948) positron emission tomography (PET), structural magnetic resonance imaging (T1‐weighted) and cognitive testing.ResultOur univariate linear mixed effect models showed there were several significant associations between the plasma biomarkers with imaging and cognitive measures. However, when all biomarkers were included in the same multivariate linear mixed effect models, we found that increased longitudinal amyloid‐PET signals were independently predicted by low baseline plasma Aβ42/40 (p = 0.011), whereas increased tau‐PET signals, brain atrophy and worse cognition were independently predicted by high plasma P‐tau217 (p < 0.004). These biomarkers performed equally well or better than the corresponding biomarkers measured in the cerebrospinal fluid and showed a similar performance to binary plasma biomarker values, which can be more easily implemented in the clinic and were defined using the Youden index as the optimal cut‐offs that could discriminate a sample of Aβ‐negative cognitively normal individuals from AD dementia patients. In addition, plasma Aβ42/40 and P‐tau217 did not predict longitudinal changes in patients with a non‐AD dementia.ConclusionIn conclusion, our findings indicate that plasma Aβ42/40 and P‐tau217 could be useful in clinical practice, research and drug development as prognostic markers of future AD pathology.
Breast cancer therapies reduce risk of Alzheimer’s disease and dementia: A claims‐based retrospective study with clinic to bench implications
Authors: Branigan Gregory L , Torrandell‐Haro Georgina , Brinton Roberta Diaz 
Published: December 2021

AbstractBackgroundWorldwide, breast cancer is the most common non‐skin cancer in women. Currently, Alzheimer’s disease affects 1 in 9 persons in the US over the age of 65, two thirds of whom are women. The high global prevalence and economic impact of Alzheimer’s disease presents a significant public health challenge while the identification of therapies to prevent Alzheimer’s disease (AD) remains a challenge. The object of this study was to determine whether estrogen modulating therapy (EMT) exposure is associated with risk of Alzheimer’s (AD) in women with breast cancer in the Symphony claims data set and identify potential mechanisms by which these drugs may impact risk.MethodsPatients receiving EMT for breast cancer treatment were identified and survival analysis, stratified by age and by individual therapeutics, was used to determine the association between EMT exposure and diagnosis of AD. A propensity score approach was used to minimize measured and unmeasured selection bias. The impact of the impact of EMT on mitochondrial bioenergetics and dynamics were determined using Metabolic flux analysis and live cell imaging using Rat E18 hippocampal neurons.ResultsIn this cohort study of propensity score matched perimenopausal to postmenopausal aged women with breast cancer, EMT exposure was associated with decrease in diagnosis of neurodegenerative disease, most specifically AD (RR, 0.85; 95% CI, 0.78‐0.92; P < 0.001) and Dementia (RR, 0.88; 95% CI, 0.84‐0.93; P < 0.001). The preventative effect of EMT was shown to increase with age and was associated with a 5‐year shift in disease conversion rate. Mitochondrial bioenergetic data suggest that tamoxifen and the aromatase inhibitors show estrogen‐like response.ConclusionAmong female patients with breast cancer, exposure to estrogen modulating therapies was associated with a decrease in diagnosis of AD and Dementia. If tamoxifen and aromatase inhibitors are acting to increase estrogen‐related actions in brain tissue, the argument for the protective association of estrogen with AD‐related outcomes is strengthened. Funding: This study was supported by grants from the Women’s Alzheimer’s Movement, National Institute on Aging grants P01AG026572 Perimenopause in Brain Aging and Alzheimer's Disease and T32AG061897 Translational Research in AD and related Dementias (TRADD) to RDB.
Individual classes of prostate cancer therapies impact risk of Alzheimer’s disease: A claims‐based retrospective study
Authors: Branigan Gregory L , Torrandell‐Haro Georgina , Brinton Roberta Diaz 
Published: December 2021

AbstractBackgroundProstate cancer is the most prevalent non‐skin cancer in men and the second leading cause of cancer related deaths among men worldwide. There are growing concerns regarding a potential association between androgen targeting therapeutic exposure and Alzheimer’s disease (AD) where the existent literature is limited and highly controversial. The object of this study was to determine whether androgen targeting therapy (ATT) exposure is associated with risk of Alzheimer’s (AD) in men with prostate cancer in the Symphony claims data set.MethodsPatients receiving ATT for prostate cancer treatment were identified and survival analysis, stratified by age and by individual therapeutics, was used to determine the association between EMT exposure and diagnosis of AD. A propensity score approach was used to minimize measured and unmeasured selection bias. Individual classes of ATT were examined to determine risk impact profiles for each therapeutic target of hormone ablation in prostate cancer treatment.ResultsIn this cohort study of propensity score matched men, all ATT class exposure taken together was associated with no impact in diagnosis of neurodegenerative disease (RR, 1.01; 95% CI, 0.96‐1.07; P = 0.56). The class of androgen synthesis inhibitors were associated with a decreased risk of AD (RR, 0.61; 95% CI, 0.46‐0.80; P < 0.001) whereas the class of androgen receptor blockers were associated with an increased risk of AD (RR, 1.29; 95% CI, 1.13‐1.34; P < 0.001). All other classes of ATT were associated with increased AD risk.ConclusionAmong male patients with prostate cancer, exposure to the androgen synthesis inhibitor class of androgen targeting therapy was associated with a decrease in diagnosis of AD and Dementia. All other types of ATT were associated with an increased risk of AD diagnosis. These data help to explain the current controversies in the literature where groups reporting impact of ATT as a composite of each individual drug suggest contradicting results on AD risk. Funding: This study was supported by grants from the Women’s Alzheimer’s Movement, National Institute on Aging grants P01AG026572 Perimenopause in Brain Aging and Alzheimer's Disease and T32AG061897 Translational Research in AD and related Dementias (TRADD) to RDB.
Mitigation of cognitive decline and brain pathology after transaortic constriction by Mas agonists
Authors: Reyes‐Reyes Elsa M , Jadhav Sachin , Soto Maira , Gaffney Kevin , Rodgers Kathleen E 
Published: December 2021

AbstractBackgroundMas and A(1‐7), the endogenous ligand of Mas, were first characterized for their ability to counter regulate the pathological actions of A‐II and AT1R. A(1‐7) has been shown to decrease inflammation and OS and increase cerebral blood flow reactivity. Plasma A(1‐7) levels were decreased in AD patients as compared to age and gender matched controls. Intra‐cerebroventricular (ICV) infusion of A(1‐7) improved cognitive and cerebrovascular function in mice receiving ICV infusion of A‐II. In SAMP8 and in P301S mice, low brain levels of A(1‐7) were correlated with increased tau hyperphosphorylation. However, the short half‐life and lack of oral bioavailability of A(1‐7) make it challenging to develop as a therapeutic modality. In order to overcome this shortcoming, our lab has developed equipotent small molecule analogs of A(1‐7), RASRx1902 and RASRx1911.MethodC57/Bl6 mice underwent transaortic constriction (TAC). One week later, echocardiography was performed and the animals randomized based on their TAC gradient and treatment (vehicle or 2 mg/kg RASx1902 or RASRx 1911 subcutaneously, once daily for 12 weeks. After 10 weeks of treatment, the mice underwent novel object recognition. At necropsy, brain tissue was analyzed by flow cytometry and levels of inflammatory cytokines by MSD.ResultTAC surgery alone resulted in reduced cognitive function measured by NOR. This cognitive decline was reversed by RASRx1902 and RASRx1911 treatment. Treatment with RASRx1902 and RASRx1911 also reduced the levels of microglial and neuronal mitochondrial dysfunction, oxidative stress (OS) and inflammation seen in saline treated mice to levels comparable to sham controls.ConclusionIn conclusion, RASRx1902 and RASRx1911 resulted in improved cognition and reduced OS and inflammation in the brain of mice that had undergone TAC surgery.
Measuring the developmental relationship between memory ability and organization of a functional brain network vulnerable to Alzheimer’s disease: Preliminary findings from the PRANK study
Authors: Behm Lillian , Phipps Connor J. , Sexton Jennifer N. , DeCesare Thomas A. , Heller Abi M. , Maerlender Arthur C. , Phatak Vaishali S. , Cramer Justin A. , Blair James , Murman Daniel L. , Warren David E. 
Published: December 2021

AbstractBackgroundThe hallmark memory impairments of typically presenting Alzheimer’s disease (AD) are associated with pathological changes of the hippocampus. While it is known that the hippocampus is necessary for normal relational memory performance, the development of functional brain networks associated with the hippocampus is not well characterized, particularly in the periadolescent epoch. The development of the hippocampus and its associated functional brain network may be influenced by genetic, environmental, or other risk factors for AD, potentially creating vulnerabilities to AD in later life. This project explores the neurodevelopment of this hippocampal network to determine how individual differences in functional connectivity impact relational memory abilities during the periadolescent epoch. Here, we utilized preliminary data from the NIA‐funded Polygenic Risk of Alzheimer’s Disease in Nebraska Kids (PRANK) study, which aims to improve insight regarding how brain and cognitive development is affected by polygenic risk for Alzheimer’s disease. Our continuing study is recruiting healthy periadolescent individuals (8‐13 years of age). Here we report preliminary cross‐sectional findings from the PRANK study exploring how individual differences in hippocampal resting‐state functional connectivity (RSFC) covary with declarative/relational memory ability.MethodAnalyses were conducted on preliminary data from healthy periadolescent participants (n=40). Declarative/relational memory performance was measured with Cambridge Cognition’s Paired Associates Learning (PAL) task. Resting‐state functional MRI data was analyzed using a seed‐based approach with the bilateral hippocampus as the seed region of interest. RSFC data were analyzed to determine their covariance with relational memory ability (operationalized as PAL performance).ResultOur analysis revealed patterns of hippocampal RSFC that were broadly consistent with prior work, sharing the territory of the default mode network (DMN). We also observed regional covariance between hippocampal RSFC and performance on the PAL task.ConclusionThe present work describes preliminary findings of the ongoing PRANK study. Our preliminary observations are consistent with the perspective that hippocampal RSFC covaries with hippocampal‐dependent declarative/relation memory ability among periadolescent children. To understand whether this hippocampal network development is susceptible to genetic risk factors for AD, future work from the PRANK study will utilize participants’ AD polygenic risk scores to determine whether those scores are related to individual differences of hippocampal RSFC.