bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review of the impact of menopause symptoms on longevity
Authors: Andrews Robin , Lacey Arron , Bache Kate , Kidd Emma J 
Published: December 2023

AbstractBackgroundEmerging evidence suggests that experiencing specific symptoms during menopause can heighten risks of developing conditions which can impact lifespan and long‐term vitality including dementia, cardiovascular disease, psychiatric conditions and cancer. In addition, it is now recognised that, while women live on average about 5 years longer than men, they often have poorer health which could be linked to this increased risk. The aim of the present review was to assess past literature to understand how distinct menopausal symptom presentations can impact lifespan and propensity for developing life‐limiting conditions.MethodThe following databases were searched: Google Scholar, EMBASE, MEDLINE, Cochrane Library, Scopus, PubMed, and Web of Science. Keys words aimed to capture factors relating to menopause, menopausal symptoms, mortality, and life limiting conditions such as Alzheimer’s disease, dementia, cardiovascular disease, stroke, cancer, liver disease, and suicide susceptibility.ResultFindings suggested that cognitive symptoms experienced during menopause were related to heightened risks of developing Alzheimer’s disease, mild cognitive impairment, dementia, and premature mortality. Vasomotor symptoms were related to increased risks of stroke and cardiovascular disease mortality. Psychological symptoms during the menopause transition were related to increased suicide risks and cardiovascular disease. Sleeping problems during menopause were related to heightened risks of cardiovascular mortality, cancer‐related mortality, and premature death from all causes.ConclusionThese findings warrant further investigation through robust analyses of public health data, to evaluate whether these outcomes are replicated within the general population. Should these findings endure, these outcomes suggest a need to improve the health of women during midlife, as doing so may prolong wellness in later life and also have consequences for socioeconomic costs. Furthermore, clarifying these associations may enable women and their health providers to recognise whether they are at risk of developing life‐limiting conditions, thus enhancing their vitality by increasing their likelihood of accessing preventative or early interventions and treatments.
Precision and Accuracy of a Novel Cognitive Battery for Use in Alzheimer’s Disease Clinical Trials: The NOMAD Study
Authors: Goldberg Terry E. 
Published: December 2023

AbstractBackgroundMany of the established measures used in current AD trials were developed for use in dementia populations. They may lack sensitivity to more subtle declines in earlier stages of the disease, be prone to practice effects (sometimes called learning effects), cause misalignment of biomarker and cognitive scores, have unknown or suboptimal psychometrics, may be prone to ceiling effects, and do not map onto neural systems. Informant based measures of function may increase uncertainty around bias, if the informant is inaccurate in report, biased, or if there is “functional unblinding” of the study drug. Here we address these problems and offer solutions to improve precision and accuracy of these outcome measures using a novel cognitive test battery and a novel performance‐based test of everyday function in the NIA funded multi‐site NOMAD study.MethodsDesign: Using a clinical trials structure one randomized group received novel measures (N Back, Brown Peterson, Fluency, Recognition Memory, Letter‐Number Span, Symbol Digit) and the other group received established measures (PACC, ADAS Cog) to reduce interference. Participants: 145 cognitively unimpaired or early MCI in each group. Serial assessments were conducted at baseline, 3 months, and 12 months.ResultsBaseline data revealed that the novel tests did not have ceiling effects, had excellent test‐reliability, had an interpretable factor structure, and were associated with AD related risk factors and biomarkers, including age, early MCI, APOE e4, and cortical volume. Additionally, they were sensitive to educational level but not sex. Examination of longitudinal data from 3 serial assessments over a 12‐ month period suggested markedly attenuated practice effects when compared to more established measures such as the PACC and ADAS‐ Cog.ConclusionNovel measures demonstrated high test‐retest reliability, sensitivity to important AD related biomarkers and demographics, and attenuated practice effects. These results suggest that we met important aims having to do with precision and accuracy— test measurements were reproducible and measured what they were designed to measure, based on factor structure, associations with AD risk factors, and reduced practice effects that would otherwise confound measurement accuracy.
user experience and redesign of a cognitive stimulation web lab for older people with and without mild cognitive impairment
Authors: Moreno Maria Celeste López , Vivas Leticia , Sarmiento Araceli Elsa Revollo 
Published: December 2023

AbstractBackgroundLABPSI is a cognitive stimulation web laboratory (labpsi.mdp.edu.ar/ejercicioscognitivos). We present here the results of the redesign process based on user experience (UX).MethodSample comprised 40 older adults with an average age of 73 years, from the city of Mar del Plata, Argentina, with and without cognitive impairment, who used the LABPSI on tablets and cell phones. Within the framework of the Mobile Goal Questions metrics (Hussein, 2012) we registered the participants´ performance in three activities. We recorded the correct steps achieved, the mistakes made, and, for tasks 2 and 3, the correct steps in a specific time frame, obtaining 13 measures. These measures were registered before and after the lab´s redesign with different participants in order to avoid learning effect.ResultA Mann Whitney U test was performed. First, we compared the performance before and after the redesign for both groups.The MCI group showed significant results in almost all the measures except for the completion of task 3, whose result was very close to the value of significance (p = .064).The group of people without MCI showed significant results in 10 measures, indicating that they improved their performance in the majority of the tasks with the exception of task 3 where they maintained the same amount of errors (p = .386), correct steps (p = .064) and steps in 5 minutes (p = .164).Then we compared the performance between people with MCI and without MCI in the redesigned version of the lab and we only observed differences in three measures: number of steps achieved in task 1 (p<.05); number of steps achieved and errors in task 2 (p<.05).ConclusionThe results show the importance of the UX analysis in the design of cognitive stimulation web labs for elderly people. In the case of the modifications implemented in the LABPSI, the laboratory´s current version proved to be accurate and improve performance for older people with and without MCI.
Anticholinergic burden and polypharmacy in primary care referrals to tertiary outpatient clinics in Brazil
Authors: Castilhos Raphael Machado , Formoso Carolina Rodrigues , Borelli Wyllians Vendramini , Teixeira Elaine Calumby , Dousseau Gabriella , Chaves Marcia L Fagundes , Brucki Sonia Maria Dozzi 
Published: December 2023

AbstractBackgroundAnticholinergic burden (ACB) and polypharmacy are associated with cognitive/functional impairment in the elderly and their frequency in primary care has been poorly studied in Brazil. We aimed to evaluate the frequency ACB/polypharmacy and association with cognitive impairment in two large tertiary care outpatients memory clinics in Brazil.MethodsWe retrospectively analyzed records of referrals from primary care to two tertiary outpatients memory clinics in Brazil (Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre and Hospital Santa Marcelina (HSM), São Paulo) from 2014 to 2022. Sociodemographic, clinical and medications in use in the first appointments were recorded. The ACB was calculated using the Brazilian Anticholinergic Activity Drug (BAAD) score, which classified drugs according to their central anticholinergic activity from 1 to 3, with higher values indicating greater anticholinergic activity. The BAAD score was dichotomized as = 0 or ≥ 1. Polypharmacy was defined as ≥ 5 drugs. A logistic regression was performed using age, sex, education, disease duration, dementia etiology, center and Mini Mental State Examination (MMSE) as covariates.ResultsAmong 980 referrals (HCPA = 429; HSM = 551), 602 (64.9%) had a final diagnosis of dementia, HCPA = 226 (56.1%); HSM = 376 (71.8%); p<0.001. Alzheimer’s disease, 93 (21.7%) and multifactorial dementia, 109 (19.8%), was the most common dementia diagnosis in HCPA and HSM, respectively. Most patients, 666 (74%), had BAAD ≥ 1 and nearly half 438 (48.7%) had polypharmacy, with no difference between centers (Table 1). BAAD was not different between diagnoses, but polypharmacy was more frequent in vascular (71, 63.4%) and multifactorial (82, 59.9%) dementia. BAAD was associated with MMSE (OR 0.95, IC 95% 0.93‐0.97) and polypharmacy (OR 3.71, IC 95% 2.66‐5.24). In addition to BAAD, polypharmacy was also associated with female sex (OR 1.45, IC 95% 1.09‐1.91) and age (OR 1.01, IC 95% 1‐1.02).ConclusionMost patients referred from primary care were using some drug with anticholinergic activity and almost half had polypharmacy, which suggests liberality in the prescription of medications in this context.
Value of hope in dementia care: what if hope is an omitted benefit in economic evaluation?
Authors: Nguyen Kim Huong 
Published: December 2023

AbstractQuality of life has been perceived as the ultimate outcome of dementia treatment and care, from patient, family, clinical and policy perspectives. Increasingly, there emerges evidence that the utility gain/loss from quality of life changes might not capture a critical function of dementia care: hope. Hope may be an important missing value from utility estimate, which is the key outcome measure in determining whether or not an intervention entails valued care.Most standard quality of life (EQ5D, HUI) and dementia‐specific measures (QoL‐AD, DEMQoL) do not directly capture hope. They might indirectly capture an aspect of hope that is correlated with self‐reported anxiety, depression or despair. Quality of life reflects the static state of health and immediate satisfaction derived from a particular health state. It does not cover the “forward looking” aspect that is embedded in hope. Furthermore, quality of life does not contain the dynamic nature of hope as a way of thinking ‐ a cognitive process.The ISPOR task force recently proposed to include hope as a novel element in the evaluation framework in decision making and health technology assessment [Lakdawalla2018]. Here, hope was framed around the risk‐aversion aspect, following two studies of cancer patients [Lakdawalla2014, Hauber2020]. This is a narrow understanding of hope, and strongly links to the prospect of being cured and/or prolonging life until a cure is found.In this study, we hypothesize that hope in dementia carries a weak link to “risk preference” yet strong association with the cognitive process underlying agency, resilience, and independence. Through the human rights lens, we apply the capability framework [Amartya Sen] to bring out the cognitive process aspect of hope, and propose a dementia‐specific measure of hope. This will also capture the lived experience of patients and families throughout care and when the care outcome is realized.From both economic and policy perspectives, if the lived experience of hope in dementia could be captured through utility measures, then “hope” will no longer be a missing source of value when evaluating dementia care. This will lead to improved efficiency of resource allocation in favour of novel approaches to care.
Microstructure of White Matter, Probed With Diffusion MRI Modeling, Reveals Distinct Correlations Between Intra‐ vs Extra‐Cellular Spaces and Tau Load
Authors: Pavan Tommaso , Ribaldi Federica , Pievani Michela , Jovicich Jorge , Garibotto Valentina , Frisoni Giovanni B , Jelescu Ileana O 
Published: December 2023

AbstractBackgroundIn Alzheimer’s disease, pathological phosphorylation of tau protein destabilizes microtubules affecting the neural cytoskeleton organization (Kolarova et al., 2012). In this study, we investigated correlates of Alzheimer’s tau pathology and white matter (WM) microstructure using diffusion MRI (dMRI) advanced models to detect tau‐related tissue changes and their trends across brain regions.MethodTen cognitively impaired subjects (age:70±7,M/F:6/4,MMSE:27.8,CI) and 11 cognitive unimpaired (age:62.4±9,M/F:1/10,CU) were recruited in the context of the COSCODE research project (Ribaldi et al., 2021). Tau standardized uptake value ratio (SUVR) was assessed from 18F‐flortaucipir PET in entorhinal, lateral‐occipital, inferior‐temporal cortex, and amygdala (reference: cerebellar crus; Mishra et al., 2017). dMRI scans were collected at 7T. WM microstructure analysis included: diffusion tensor (DTI), kurtosis tensor imaging (DKI, Jensen and Helpern, 2010), and a biophysical model of WM microstructure (WMTI‐Watson, Fig.1, Jespersen, et al., 2018). Mean values for each diffusion metric were calculated in WM ROIs of the JHU atlas (Mori et al. 2005) and correlated to tau across CI subjects (statistical significance: p<0.05).ResultCorrelation analysis showed a systematic disconnect between diffusion metrics parallel and perpendicular to the axons: RD (and MD) correlated positively with tau, while AD negatively. Similarly, RK (and MK) correlated negatively, while AK positively (Fig. 2). Higher diffusivities and lower kurtosis (perpendicular to axons) are associated with less complex tissue, while lower diffusivities and higher kurtosis (parallel to axons) are associated with a more tortuous and heterogeneous environment. The biophysical model showed that higher diffusivity in the extra‐cellular space (De,//, De,

⊥
) was associated with higher tau, while axonal density (f) and within‐axon diffusivity (Da) correlated negatively.ConclusionThe significant correlations between tau and FA, RD, MD, RK and MK, are consistent with neurodegeneration. The positive correlation of De,//, De,

⊥
and negative correlation of f to tau confirms the axonal loss and the increase of extracellular diffusivity. Interestingly, the negative correlation of tau to water diffusivity within the axons (Da) could be explained by microtubules breakdown and intra‐axonal deposition of neurofibrillary tangles that impede water diffusion. These evidences of dMRI microstructure correlation with tau SUVR may be useful to detect the in‐vivo neurodegeneration.
Sex and family history differences in Aβ and tau vulnerability in preclinical Alzheimer’s disease
Authors: Ourry Valentin , St‐Onge Frederic , Mohammediyan Bery , Yakoub Yara , Soucy Jean‐Paul , Poirier Judes , Breitner John C.S. , Villeneuve Sylvia 
Published: December 2023

AbstractBackgroundFemales and individuals with a family history (FH) of Alzheimer’s disease (AD) are considered at higher risk of sporadic AD. However, how sex and maternal/paternal heredity affects in vivo AD biomarkers is not well understood. Our objectives were to 1) assess if females or individuals with a first‐degree maternal FH of AD accumulate amyloid‐beta (Aβ) and/or tau faster than males or individuals with a first‐degree paternal FH of AD and 2) assess if both could influence the rate of Aβ driving tau in preclinical AD.MethodTwo hundred and thirty‐five older adults (age 68.3 ± 5.1 years, 69.8% female) from the PREVENT‐AD cohort, cognitively unimpaired at baseline, underwent [18F]‐NAV4694 and [18F]‐AV1451 positron emission tomography (PET) scans. Longitudinal PET scans were available for 106 individuals (4.3 ± 0.4 years follow‐up). We extracted and averaged the standard uptake value ratio (SUVr) in fronto‐parietal regions for Aβ and in temporal regions for tau. We performed t‐tests and ANOVA models to assess sex or maternal/paternal FH (FHsex) differences in Aβ and tau burden or annual change. We then performed linear regression models with an interaction term between Aβ and sex (or Aβ and FHsex) on tau burden and annual change, plus additional models to adjust for age and education.ResultSex and FHsex differences on Aβ and tau burden or annual rate of change did not reach significance although females tended to have higher tau SUVr at baseline (p = 0.053) (Figure 1 & 2). We found an interaction between Aβ and sex (𝛽 = ‐0.13, p = 0.008), and between Aβ and FHsex (𝛽 = 0.11, p = 0.03), on tau at baseline (Figure 3) suggesting that, for the same level of Aβ burden, females and individuals with paternal FH of AD had higher tau burden than males and individuals with maternal FH of AD. Results were similar when adjusted for age and education.ConclusionFemales and individuals with a paternal FH of AD might need less Aβ before developing AD‐related tau, but did not accumulate tau faster. Identifying individuals more vulnerable to AD pathology, by disentangling sex‐specific effects, would help to design personalized interventions for AD.
Immunohistochemical and behavioral assessment of FKBP51‐Hsp90 interaction‐deficient mouse crossed with Alzheimer tau transgenic Tg4510 mice
Authors: Winblad Bengt , Wang Lisha , Zhao Zhe , Sun Xuelian , Shimozawa Makoto , Nilsson Per , Pavlov Pavel F. 
Published: December 2023

AbstractBackgroundFK506‐binding protein 51 kDa (FKBP51) is a heat shock protein 90 (Hsp90) associated co‐chaperone which has recently emerged as a possible Alzheimer disease (AD) therapeutic target involved in tau metabolism. 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. To elucidate the role of FKBP51‐Hsp90 complex in tau biology in vivo we have crossed well characterized tau transgenic Tg4510 mice with our novel FKBP51‐Hsp90 interaction‐deficient mice (Fkbp5TPRmut).Methods• Using PCR amplification, we have confirmed correct genotype of crossings.• Immunohistochemical staining of brains of 4 months‐old animals with total tau and phospho‐tau antibodies.• Behavior assessment of cognition and memory using open field, novel object recognition, Y‐maze, and fear conditioning tests.Results• Successful crossings between Fkbp5TPRmut and Tg4510 mice have been obtained• We have confirmed phospho‐tau expression in the cortex and hippocampus of 4 months‐old transgene‐expressing animals (positive controls).• Immunohistochemical assessment of phospho‐tau expression in the cortex and hippocampus of wild‐type and Fkbp5TPRmut x Tg4510 crossings is ongoing.• Behavioral assessment of Wt x Tg4510 and Fkbp5TPRmut x Tg4510 crossings is ongoing.Conclusion• Fkbp5TPRmut crossings with Tg4510 mice do not display harmful phenotype.• Behavioral and immunohistochemical evaluation experiments are ongoing and will soon be completed.
The prioritization of biomarkers in the diagnostic workup of Lewy body disease
Authors: Aarsland Dag 
Published: December 2023

AbstractThe term Lewy body disease (LBD) encompasses a spectrum of neurodegenerative conditions, particularly Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB), associated with abnormal deposits of alpha‐synuclein in the brain and representing up to 20% of all neurocognitive disorders in memory clinics. Mild cognitive impairment or mild dementia precede or concur with Parkinsonism in the early stages of DLB and in a third of patients with PD at diagnosis. However, when Parkinsonism is slightly detectable, the differential diagnosis from other dementing conditions, such as Alzheimer’s disease (AD), may be challenging. For this reason, neuroimaging and electrophysiological biomarkers, divided into indicative or supportive based on their diagnostic performance over or below 80%, assist the clinical reasoning to increase the likelihood that MCI/early dementia is associated with LB. The European Intersociety Consensus Diagnostic Task Force recommends prioritizing the Dopamine transporter (DaT)‐SPECT imaging to investigate nigro‐striatal degeneration as the first biomarker (sensitivity 76%, specificity 88%), and suggests subsequently [123I]‐MIBG cardiac scintigraphy to evaluate the postganglionic sympathetic denervation in those cases (about a quarter) where DaT‐SPECT is negative but DLB is still clinically possible (AD pathology is estimated to be underlying in about 86% of these cases). In the absence of well‐validated techniques to establish the presence of brain alpha‐synuclein aggregates in vivo, the proposed sequence of biomarkers will provide the most accurate and cost‐effective biomarker‐based diagnosis of LBD.
Oligodendrocytes and Oligodendrocyte Precursor Cells (OPCs) in aged human brain. A Neuropathology study.
Authors: Hainsworth Atticus H , Bridges Leslie , Jeevahan Jamuna , Fang Wen Yung Stephanie , Keefe Jemma 
Published: December 2023

AbstractBackgroundCerebral Small Vessel Disease (CSVD) represents a variety of pathological processes affecting the cerebrovascular system. We tested whether the populations of oligodendrocytes (OLs) and oligodendrocyte precursor cells (OPCs), associate with ageing and with CSVD.MethodWe examined deep subcortical white matter of individuals aged 78.5 (18.3) (mean (SD); range 20‐97, n = 24 (no information were given for 2 of them, only ‘young’)) with and without CSVD. All had minimal AD pathology (Braak stage II or less). Immunohistochemistry was performed, using the markers NogoA (specific for mature OLs), CD140A (for OPCs) and Sox10 (both OPCs and OLs) followed by digital image analysis.ResultAll samples had a substantial density of small, parenchymal cells with robust expression of each marker (NogoA, CD140A, Sox10). The density of NogoA‐positive cells was correlated with age (rs = 0.619, p = 0.011). There was a lower density of CD140A‐positive cells in individuals aged >70 with CVSD compared to those without CVSD (p = 0.016).ConclusionOur results indicate that there may be changes in OL and OPC density with age, and in CSVD.