bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of intensive blood pressure reduction for the prevention of cognitive decline and dementia: A systematic review and meta‐analysis
Authors: Dallaire‐Théroux Caroline , Quesnel‐Olivo Marie‐Hélène , Brochu Karine , Bergeron Frédéric , Laforce Robert , Verreault Steve , Camden Marie‐Christine , Duchesne Simon 
Published: December 2021

AbstractBackgroundHigh blood pressure is a treatable, high risk factor for both cerebrovascular disease and cognitive impairment. Antihypertensive treatment can be viewed therefore as a potential approach to reduce dementia risk. We aimed to examine the effectiveness and safety of intensive, as opposed to standard, blood pressure reduction in adults with hypertension for the primary or secondary prevention of cognitive decline and dementia.MethodsWe conducted a systematic review and meta‐analysis of randomized controlled trials reporting on intensive versus guideline blood pressure targets and cognitive outcomes by searching MEDLINE (Ovid), Embase (Embase.com), CENTRAL, Web of Science, CINAHL, PsycINFO (Ovid), ICTRP and ClinicalTrials.gov databases up to October 27, 2020. Titles and abstracts screening, full‐texts review, data extraction, and risk of bias assessment were performed in duplicates. Conflicts were resolved by an independent reviewer. Our primary outcome was cognitive decline from baseline. Secondary outcomes included incidence of dementia, mild cognitive impairment, cerebrovascular events, serious adverse events, and mortality.ResultsWe identified five trials (17,396 participants), reported in fourteen publications meeting our inclusion criteria among 7,755 screened citations. The mean follow‐up duration was 3.3 years (range 2.0 to 4.7 years). Intensive blood pressure reduction was not associated with a significant change in global cognitive performance at follow‐up (SMD 0.01, 95% CI ‐0.04 to 0.06), incidence of dementia (RR 1.09, 95% CI 0.32 to 3.67) or incidence of mild cognitive impairment (RR 0.91, 95% CI 0.73 to 1.14) when compared to standard treatment. However, we found a significant reduction of cerebrovascular events in the intensive treatment arm (RR 0.79, 95% CI 0.67‐0.93), with no increased risk of serious adverse events (RR 1.13, 95% CI 0.91‐1.40) or mortality (RR 0.93, 95% CI 0.75‐1.15).ConclusionsWe found insufficient evidence to justify more intensive blood pressure reduction for the prevention of cognitive decline and dementia in adults with hypertension. Prospective, randomized trials with longer follow‐ups may be necessary to highlight such potential benefits.
Emotion characteristics of older adults with MCI among a socially isolated cohort using NIH toolbox: I‐CONECT Study
Authors: Yu Kexin , Wild Katherine , Silbert Lisa C , Kaye Jeffrey A , Dodge Hiroko H 
Published: December 2021

AbstractBackgroundA diagnosis of Mild Cognitive Impairment (MCI) has been found to be associated with changes in emotional wellbeing and social relationships. Socially isolated older adults with MCI are at greater risk of developing Alzheimer's Disease and Related Dementias. Better understanding the emotional functioning of individuals with MCI could inform the development of behavioral health interventions. Within a socially isolated sample of older adults, this study compares psychosocial wellbeing of older adults with MCI to their cognitively normal counterparts.MethodsThis cross‐sectional study uses baseline data from the Internet‐based Conversational Engagement Clinical Trial (I‐CONECT, ClinicalTrials.gov: NCT02871921). Eligible participants were ages 75 or older and were socially isolated as defined by scoring <12 on the 6‐item Lubben Social Network Scale, engaging in conversations lasting 30 minutes ≦ twice per week, or answering "Often" to at least one question of the three‐item UCLA Loneliness Scale. MCI status was determined according to clinical diagnosis. This working sample includes the first 127 participants whose baseline emotion battery scores were available as of November 2020. Based on NIH Toolbox scoring instructions, three domain scores were calculated with the 17 emotion measures, i.e., negative affect, social satisfaction, and psychological wellbeing. Linear regressions were conducted for all 17 Emotion Battery measures and 3 domain scores, controlling for age, gender, education, and severe depressive symptoms. Severe depressive symptom was operationalized as scored ≧5 on the 15‐item Geriatric Depression Scale (GDS).ResultsParticipants' mean age was 81.1 (SD=4.6); 69.9% of the participants were female; and mean years of education was 15.2 (SD=2.3). 54% of the participants were diagnosed with MCI. The average GDS score was 2.3 (SD=1.8). For the three major emotion domains assessed, older adults with MCI had more negative affect, yet no difference was observed in social satisfaction and psychological wellbeing (see Table 2). More specifically, compared to cognitively normal older adults, individuals with MCI had higher levels of fear, perceived hostility, perceived stress, sadness, and lower self‐efficacy.ConclusionThe study's findings indicate that older adults with MCI experience more negative emotions than cognitively normal older adults. However, there were no between‐group differences observed in positive emotions.
Deep sleep predicts the cognitive evolution of mild‐moderate Alzheimer’s disease patients
Authors: Targa Adriano , Benitez Ivan David , Dakterzada Faride , Minguez Olga , Barbe Ferran , Piñol‐Ripoll Gerard 
Published: December 2021

AbstractBackgroundTo investigate the association between sleep and the cognitive evolution of mild‐moderate Alzheimer’s disease patients.MethodObservational, prospective, single‐center study, including consecutive patients diagnosed with mild‐moderate Alzheimer’s disease (NCT02814045). The individuals were submitted to overnight polysomnography, followed by neuropsychological evaluations at baseline and after 12 months of follow‐up. Principal component analysis characterized the sleep architecture of the cohort into two main types: individuals with a propensity to deepen their sleep (deep sleepers) and individuals who spent most of the time in the lighter sleep stage (light sleepers).ResultThe cohort included 125 subjects with a median [IQR] of 75.0 [72.0;80.0] years. The mean difference (95% CI) in the Mini‐mental state examination score at 12 months between deep and light sleepers was ‐1.51 (95% CI: ‐2.47 to ‐0.54; p‐value = 0.002). Accordingly, sleep depth and cognitive evolution presented a dose‐response relationship (p‐for‐trend = 0.02). Regarding the specific cognitive subdomains, we observed differences related to the processing speed, demonstrated by the Stroop words test (‐1.48; 95% CI: ‐2.58 to ‐0.38; p‐value = 0.009), and to the executive function, demonstrated by the Verbal fluency test (‐1.70; 95% CI: ‐2.85 to ‐0.55; p‐value = 0.004).ConclusionConsidering that light sleepers presented an increased cognitive decline, the sleep profile may have a predictive role in the cognitive evolution of mild‐moderate Alzheimer’s disease patients. The modifiable nature of sleep sets this behavior as a possible useful intervention for the improvement of cognitive evolution.
Empirically derived composite cognitive test scores to predict preclinical and clinical stages of Alzheimer’s disease
Authors: Shishegar Rosita , Chai Tze Young , Cox Timothy , Lamb Fiona , Robertson Joanne S. , Laws Simon M. , Porter Tenielle , Fripp Jurgen , Doecke James D. , Tosun‐Turgut Duygy , Maruff Paul T. , Savage Greg , Rowe Christopher C. , Masters Colin L. , Weiner Mike W. , Villemagne Victor L.L. , Burnham Samantha C. 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) clinical trials require cognitive test scores that assess change in cognitive function accurately. Here, we propose new composite cognitive test scores to detect earlier stages of AD accurately by using the full neuropsychological testing battery (in ADNI) and a manifold learning dimension reduction technique namely UMAP.MethodData for this study included N=1585 ADNI participants ([492 cognitively normal (CN), 804 mild cognitively impaired (MCI), 289 AD; aged 73.8±7.1; 708 females]; Table 1). Subjects with 3 or more follow‐up sessions were included. Cognitive test scores with more than 60% missing data were excluded. Missing data within included test scores were imputed using the MissForest algorithm. A linear mixed model using all follow‐up data was applied to calculate the random slope (rate of change) and random intercept for each cognitive score and for each subject. The scores and demographic measurements: age, gender, years of education and APOE‐ɛ4 status were used to inform the UMAP. Levels for the output variable were defined as: 1) stable CN, 2) CN who progressed to MCI or probable dementia due to AD, 3) stable MCI, 4) MCI who progressed to dementia AD and 5) dementia due to AD. The model calculated two composite scores. These cognitive stages were predicted using Support Vector Machine (SVM) analysis of both the new composite scores and the traditional clinical rating measures of Clinical Dementia Rating (CDR) and Mini‐Mental State Examination (MMSE).ResultPredicting cognitive stages using the proposed composite scores show a highly significant improvement with a 0.981 accuracy and 0.976 reliability (evaluated by Cohen's kappa coefficient), compared to using the combination of CDR and MMSE scores covaried for demographics, which had 0.660 accuracy and 0.567 reliability. Individuals’ clinical and preclinical stages with regards to UMAP two‐dimensional embedding and the clinical rating measures, CDR and MMSE, are presented in Figure 1. Table 2 reports the importance of the test measures on the UMAP components used in AD staging predictions.ConclusionThe results here suggest that the proposed empirically derived composite cognitive test scores provides a practical solution to differentiate cognitive stages with a high accuracy and reliability.
The brain correlates of behavioral disturbances in frontotemporal dementia
Authors: Fiondella Luigi , Mattioli Irene , Salemme Simone , Carbone Chiara , Vinceti Giulia , Tondelli Manuela , Chiari Annalisa , Molinari Maria Angela , Huey Edward D. , Jenkinson Mark , Grafman Jordan , Zamboni Giovanna 
Published: December 2021

AbstractBackgroundVarious studies have researched singular or clusters of behaviors in frontotemporal dementia (FTD) correlating them with regional brain atrophy in structural MRI data, or hypometabolism in FDG‐PET images, but a multimodal approach is lacking. We identify the brain correlates of modes of variation (i.e., factors) explaining the variability of behavioral and psychological symptoms (BPSD) in frontotemporal dementia (FTD) using multimodal imaging.MethodImaging and behavioral data from 93 FTD patients acquired at NIH were analyzed. They underwent extended neuropsychological assessment including several scales measuring BPSD (UCLA NPI, FrSBe, and Neurobehavioral rating scale), T1‐weighted MRI, and FDG‐PET imaging. Factor analysis was used on the behavioral data to identify modes of variation of BPSD potentially pointing to few common neurobiological substrates across the FTD sample. The identified modes were then related to intersubject brain variability using a newly developed fusion method run on maps of gray matter volume and FDG metabolism obtained.ResultA factor related to decreased emotional/cognitive interaction (loading scores of apathy, executive dysfunction, withdrawal) correlated with volume and function of the right anterior cingulate and orbito‐frontal cortex. A factor expressing variability on mutacism versus disinhibition/euphoria continuum was associated with dysfunction of the right superior primary motor cortex. A factor related to the presence of hallucinations/delusions/suspiciousness was associated with dysfunction of the right anterior insula.ConclusionBPSD variability in patients with FTD can be explained by 3 major modes of variations, each associated with intersubject brain structure/function variability of the right frontal lobe.
Analysis of cognitive and functional states with relation to variables: A quantitative study in Mauritius
Authors: Dorkhy Geeta Devi 
Published: December 2021

AbstractBackgroundTo identify the relationship between factors that accelerate cognitive or functional decline in person with Alzheimer's diseaseMethodQuantitative method, using pre‐validated MMSE questionnaire and Katz Index of Independence in ADL along with demographical data. Using SPSS and Chi‐square test to obtain p‐values and statistical relations and significance between these associations in table forms.ResultNormal cognitive function was noted in 53.7% of total sample (n=42) while normal functional states was 73.8% in same sampled population. Severe cognitive decline accounted for 26.8% and severe functional impairment was 11.9%.ConclusionAll the p‐values exceed 0.05, in association between MMSE and associated variables (gender, age, occupation, medical illness, marital status, family status, smoking and drinking habits). MMSE is not significantly associated with any of the variables at 5% level. Neither gender nor occupational status had any significant bearing on ADL at 5% level.
Changes in the awareness of cognitive decline across the course of Alzheimer’s disease: Comparison of two assessment methods
Authors: Cacciamani Federica , Valladier Arnaud , Maheux Etienne , Koval Igor , Durrleman Stanley , Epelbaum Stéphane 
Published: December 2021

AbstractBackgroundRecent studies have suggested that poor awareness of cognitive decline (ACD) could be an early indicator of Alzheimer's disease (AD). However, there is still no gold‐standard for ACD assessment. In this study, we describe longitudinal changes in ACD in subjects with biomarker‐defined AD (according to the A/T/N framework by Jack and colleagues), assessing ACD by two methods: a subject‐informant discrepancy and a subjective‐objective scores discrepancy.MethodWe included 334 amyloid‐ and tau‐positive (A+T+) subjects with normal cognition, MCI and dementia, and 137 cognitively‐normal A‐T‐ controls from the ADNI cohort, followed up for an average of 5 years. Using a statistical mixed‐effects model (Couronné & al., 2019, ISBI), we reconstructed the evolution of a composite memory score, self and informant’s assessments of cognitive functioning (E‐Cog) and two ACD measures: the ACD index (ACDI, i.e. the difference between E‐Cog‐Subject and E‐Cog‐Informant) and the Meta‐Memory Ratio (MMR, Gagliardi et al. 2019 ART, i.e. the comparison between the E‐Cog‐Subject and a composite memory score). After rescaling the scores, an abnormality threshold was calculated for each of them corresponding to the 95th percentile of the distribution of control subjects.ResultThe subject perceives, at the beginning of the disease, a cognitive decline that is not detected neither by the informant (Figure 1) nor by the tests (Figure 2). This condition can be called "hypernosognosia". The subjective cognitive decline increased slightly and became abnormal 2 years after the diagnosis of dementia. A clear anosognosia was visible starting from the MCI phase using both assessment methods. The MMR detected a reduction in ACD earlier than the ACDI: the subject passes from a hypernosognosia to a good match with the memory score between 64 and 69 years, and with the informant rating between 73 and 76 years on average.ConclusionHypernosognosia is associated with a risk of AD during a short period of time, when the disease is at a very early stage. Thereafter, the individual's ACD decreases. We will discuss the advantages and disadvantages of both assessment methods in both research and clinical practice, especially in relation to their usefulness for early detection of AD.
The risks of polypharmacy in ambulatory and home care patients affected with dementia: The PharE Study
Authors: Gareri Pietro , Russo Emilio , Condito Andrea , De Sarro Giovambattista 
Published: December 2021

AbstractBackgroundOlder patients affected with comorbidities often take a lot of potentially inappropriate drugs. This can cause side effects, hospitalization and even death.AimThe aim of the present study was to assess dangerous drug interactions and potentially inappropriate drugs administered to a sample of ambulatory and home care patients affected with dementia.Methods41 ambulatory outpatients and 53 home care patients affected with dementia were selected randomly between January 1st 2017 and December 31st 2019. They were visited at the Center for Cognitive Disorders and Dementia, Catanzaro Lido, Italy.Personal, clinical data and drugs taken were collected; comorbidities were assessed through CIRS, ADL, IADL, MMSE. Beers criteria were used in order to assess the potentially inappropriate drugs.ResultsOf 100 patients, 64 were women and 36 men, mean age 83,7 ± 4,9 and 82,1 years old ± 11,8 years old respectively. 50% of them were affected with mixed dementia, 13% Alzheimer’s dementia, 9% Parkinsonism, 10% depression with associated cognitive impairment, 18% dementia of other kind. Mean MMSE score was 15,99 ± 8,84. Each patient was taking 9,17 ± 3,31 drugs on the average, 56% of them 5‐9 drugs and 39% 10 drugs or more. 66% of patients was taking one inappropriate drugs or more, proton pump inhibitors (PPI) (51%), atypical and conventional antipsychotics (23% and 6% respectively), benzodiazepines, amiodarone, calcium antagonists (3%), tricyclic antidepressants and a‐blockers (2%), old generation anti‐histamine drugs (1%). 56% of them were taking a drug with anticholinergic properties.ConclusionsThe study shows a high percentage of drugs with anticholinergic properties, which can increase the risk for dementia or even worsen cognitive impairment. Furthermore, inappropriate drugs were stopped and changed with more tolerated compounds. PPI use was dramatically reduced. The study suggests the need for a careful check of treatment in every patient, and for personalizing treatment in older patients with dementia. A larger sample could bring more information to healthcare providers as well as the use of softwares for helping doctors to limit the risk for drug interactions.
Comparison of white matter hyperintensity abnormalities and cognitive performance in individuals with low and high cardiovascular risk: Data from the Diabetes and Dementia (D2) study
Authors: Restrepo Carolina , Patel Sheila , Khlif Mohamed Salah , Bird Laura J. , Singleton Rebecca , Yiu Chi Him Kendrick , Werden Emilio , Ekinci Elif , MacIsaac Richard , Burrell Louise , Brodtmann Amy 
Published: December 2021

AbstractBackgroundType 2 diabetes Mellitus (T2DM) is recognised as a major contributor to cognitive decline. People with T2DM demonstrate increased white matter hyperintensity (WMH) abnormalities on MRI compared to control individuals. We investigated associations between a validated vascular risk score: The Framingham Risk Score (FRS), WMH volumes and cognitive function in the Diabetes‐and‐Dementia (D2) study, a longitudinal cohort study of community dwelling people with T2DM.MethodOne hundred and twenty‐three non‐demented participants with T2DM (age 66.7±6.8 years, range 50‐80, 68M/55F) completed neuropsychological assessments, health questionnaires to allow FRS calculation, 24‐hour ambulatory blood pressure monitoring, and a 3T‐MRI scan. WMH were calculated using the functionality "run‐samseg" in FreeSurfer 7. Quality control on the traced lesions was performed using an in‐house semi‐automated MATLAB tool. Periventricular and deep WMH volumes were estimated based on the edited lesion traces. We divided participants into low (n=61) and high (n=62) FRS groups based on the median score (x=48.7). Differences in WMH volumes were compared between the FRS groups after correcting for sex and age. We compared cognitive performance between low/high FRS individuals across five composite cognitive domains: memory, language, visuospatial skills, executive function, and attention‐and‐processing‐speed. The composite score for each domain was the normalised z‐scores average for the respective tests.ResultParticipants with high FRS (implicating greater vascular risk) were significantly older (age F(1, 122)=14.97; p<0.001), were less likely to be female (sex χ2=16.73, p<0.001), and tend to have less than 12 years of education (χ2= 3.69, p = 0.041). Relative to individuals with low FRS, those with high FRS showed significantly higher WMH volumes (F(1, 121)=6.11; p=0.015). Significant differences were also identified for periventricular (F(1, 121)=6.16; p=0.014) and deep (F(1, 121)=4.25; p=0.042) WMH volumes. When the cognitive data were analysed, the low FRS group performed signifcantly better than the high FRS group only on the attention‐and‐processing‐speed factor (F(1,115)=5.17; p=0.025).ConclusionHigh cardiovascular risk, defined as a high FRS, in participants with T2DM was associated with greater WMH volume, a marker of white matter dysfunction, and with deficits in processing speed and attention. Subclinical cognitive deficits were common in our community dwelling cohort without known or preceding cognitive dysfunction.
A novel method for tracking the progression of WMHs through the alignment of premortem in‐vivo to postmortem ex‐vivo MRI and histopathology
Authors: Schweitzer Noah , Farhat Nadim , Wu Minjie , Kofler Julia , Berardinelli Jacob , Ibrahim Tamer , Iordanova Bistra , Aizenstein Howard J 
Published: December 2021

AbstractBackgroundWhite matter hyperintensities (WMHs) are neuroimaging features associated with Alzheimer’s disease (AD). Ex‐vivo studies may enable better characterization of WMHs pathological substrates. In this work, we present a novel method that leverages in‐vivo and ex‐vivo MRIs and histopathology to analyze the progression of WMHs in AD.MethodA single subject’s in‐vivo MRI scans at four different time points were analyzed. Ex‐vivo scans of the brain left hemisphere were done using 16‐Tx and 32‐Rx TicTacToe coil3 and a 3‐D printed enclosure with integrated cutting guides1 (Fig. 1). The WMHs were segmented on the T2‐weighted FLAIR in‐vivo MRI 2, and registered onto the final time point via SPM’s normalized mutual information‐based algorithm. All four WMH segmentations were warped to the ex‐vivo MRI’s space by applying the deformation field from the ITK in‐vivo to ex‐vivo registration.ResultThe 3D printed enclosure achieved an accurate alignment between gross pathology, ex‐vivo and in‐vivo MRI (Fig. 1). Then, we computed the WMHs’ growth over time warped onto the ex‐vivo MRI (Fig. 2). This growth was quantified as the total number of voxels in each segmentation longitudinally with a quadratic fit with an R2 =0.99 (Fig. 2). Lastly, we found a significant change in the distribution of WMH segmentations over time as evident by their normalized histograms (Fig. 3).ConclusionWe present a novel method to track the progression of WMHs in‐vivo to ex‐vivo MRI and gross pathology. Future studies will perform a voxel‐wise analysis on the WMHs in MRI scans, both in‐vivo and ex‐vivo, along with its histological correlates to gain insight into the underlying cellular mechanisms during the biomarker’s development. References: 1. Nadim Farhat et al. “Reusable 3D printed enclosure with integrated cutting guides for the alignment of high resolution ex‐vivo MRI with ex‐vivo gross brain photographs.” 2021 ISMRM Meeting (Under revision). 2. Wu, M. et al (2006). “A fully automated method for quantifying and localizing white matter hyperintensities on MR images.” Psychiatry Research: Neuroimaging, 148(2‐3), 133‐142. 3. T. Santini et al., “In‐vivo and numerical analysis of the eigenmodes produced by a multi‐level Tic‐Tac‐Toe head transmit array for 7 Tesla MRI,” PLoS One, vol. 13, no. 11, p. e0206127, Nov. 2018.