bluuebunny/crossref_metadata_2025_split huggingface dataset:
Findings from an Asian post‐stroke cognitive impairment intervention programme
Authors: Wong Fennie , Ng Sheng Chun , Chua Esther Vanessa , Kandiah Nagaendran 
Published: February 2022

AbstractBackgroundSingapore sees more than 7,000 ischemic stroke cases yearly, with majority having physical and cognitive sequelae. Previous reports demonstrate that Post‐stroke cognitive impairment (PSCI) occurs in 37.3% of stroke patients at the National Neuroscience Institute (NNI, Singapore) within 6 months post‐stroke. The severity of rising PSCI rates prompted the implementation of the NNI Stroke Memory Rehabilitation Programme (SMaRT) for ischaemic stroke patients with mild physical impairments. This study aims to evaluate the outcomes of the SMaRT programme on PSCI and post‐stroke coping over a 6‐month period.MethodThe SMaRT programme is a 8‐week group‐based post‐stroke cognitive rehabilitation programme focusing on healthy living habits, memory models, memory strategies and emotion regulation strategies. Patients with clinically diagnosed ischaemic strokes, mild functional and cognitive issues (modified Rankin Scale score≤3 and Mini Mental‐State Examination score≥20) were recruited from April 2018 to September 2020. Assessments were administered at baseline, 8 weeks and 6 months post‐SMaRT, measuring global cognition (Montreal Cognitive Assessment, Visual Cognitive Assessment Tool), visuospatial function/attention (Trail Making Test‐A), emotional coping (Geriatric Depression Scale‐15), daily functioning (Nottingham Extended Activities of Daily Living (NEADL)), subjective quality of life (Dementia Quality of Life (DemQOL)). Paired samples t‐tests compared scores between the three timepoints, adjusting for type I errors with Bonferroni correction.Result137 subjects (N males=90 (65.7.%); mean age=63.49 years, SD=9.38, mean years of education=9.50, SD=3.79) underwent SMaRT. Comparing week‐8 to baseline, there was significant improvement in global cognition (MoCA, VCAT: p<.001), emotional coping (GDS, p<.001), daily functions (NEADL, p<.001), subjective quality of life (DemQOL: p=.008). Significant improvement was also observed comparing month‐6 to baseline scores in global cognition (MoCA, VCAT: p<.001), emotional coping (GDS, p<.001), daily functions (NEADL, p<.001), subjective quality of life (DemQOL: p<.001). In both analyses, decreasing trends in TMT‐A (seconds) were observed and approached significance.ConclusionThe SMaRT programme is effective in mitigating post‐stroke cognitive impairment, particularly in global cognition. Additionally, SMaRT improved mood, daily functioning and subjective quality of life, suggesting its ability to instill positivity and confidence in stroke patients. These suggest a group‐based structured cognitive rehabilitation programme is likely to benefit stroke patients and reduces incidence of PSCI.
The effects of concurrent cognitive and meta‐cognitive training on neuropsychiatric symptoms of people living with younger onset dementia: Protocol for a pilot trial
Authors: Sabates Julieta M , Loi Samantha M , Lautenschlager Nicola T , Brodtmann Amy , Bahar‐Fuchs Alex 
Published: February 2022

AbstractBackgroundNeuropsychiatric symptoms (NPS) are behavioural and psychological disturbances frequent in people with dementia that have been linked with lower quality of life, lower cognitive functioning and greater caregiver distress, especially for caregivers of people with younger‐onset dementia (YOD) (1).Several drug and non‐drug treatments targeting NPS have been investigated in recent years. However, to the best of our knowledge, no treatment has been developed that concurrently targets and trains cognitive and meta‐cognitive processes which are implicated in the expression of NPS. The aim of this pilot trial is to investigate the effects on NPS of a mobile application‐based intervention simultaneously training both processes by incorporating elements of cognitive training and cognitive‐behavioural therapy.MethodTwenty participants with YOD will be randomised to the training group or to a control group. Participants in the experimental condition will train at home three times a week for four weeks with remote therapist support. NPS, cognitive, psychological and caregiver outcomes will be assessed before and immediately after the intervention.ResultThe mobile application is in the design stage and further studies are underway to incorporate the views of people with YOD and their care‐partners, as well as clinicians, to the design. Recruitment of participants is expected in the second half of 2021.ConclusionFindings from this trial will further our understanding of the utility of concurrently targeting cognitive and meta‐cognitive processes in people with YOD when treating NPS and will inform a revision of the application. We believe that results from this study will have important implications for the management and treatment of NPS in the ever‐growing field of interventions utilising technology. 1 Baillon, S., Gasper, A., Wilson‐Morkeh, F., Pritchard, M., Jesu, A. and Velayudhan, L., 2019. Prevalence and Severity of Neuropsychiatric Symptoms in Early‐ Versus Late‐Onset Alzheimer’s Disease. American Journal of Alzheimer's Disease & Other Dementias®, 34(7‐8), pp.433‐438.
Tau PET as a prognostic marker in preclinical and prodromal Alzheimer’s disease
Authors: Ossenkoppele Rik , Mattsson Niklas , Smith Ruben , Groot Colin , Cho Hanna , La Joie Renaud , Baker Suzanne L. , Borroni Edilio , Klein Gregory , Pontecorvo Michael J. , Devous Michael D. , Jagust William J. , Lyoo Chul Hyoung , Rabinovici Gil D. , Hansson Oskar 
Published: February 2022

AbstractBackgroundTau PET tracers have proven useful for diagnostic purposes, but their prognostic utility for predicting future cognitive changes over time is unclear. We aimed to examine the prognostic accuracy of [18F]flortaucipir and [18F]RO948 (tau) PET in individuals across the Alzheimer’s disease (AD) spectrum.MethodWe included 673 cognitively unimpaired individuals (CU, 277/673 amyloid‐β+), 443 participants with mild cognitive impairment (MCI, 279/443 amyloid‐β+) and 315 amyloid‐β+ participants with AD dementia. Amyloid‐β status was determined by PET and/or CSF. The participants underwent [18F]flortaucipir (n=1135, discovery cohort) or [18F]RO948 (n=296, replication cohort) PET, T1‐weighted MRI and repeated Mini‐Mental State Examination (MMSE). Baseline [18F]flortaucipir/[18F]RO948 PET standardized uptake value ratios (SUVR) within in a temporal region‐of‐interest (ROI)and an MRI‐based AD‐signature cortical thickness ROI were used to predict longitudinal changes of MMSE using linear mixed effect models. Additionally, we performed mediation analyses to test whether associations between baseline tau PET and cognitive change were mediated by baseline MRI measures, and examined whether age, sex and APOE genotype modified the association between baseline tau PET and cognitive change.ResultTau PET in a temporal ROI predicted changes in MMSE, and associations were stronger than for AD‐signature cortical thickness across all participants (R2: 0.34 vs 0.24, bootstrapped p‐value for difference: <0.001), in amyloid‐β+ MCI (R2: 0.27 vs 0.13, p<0.001) and in amyloid‐β+ CU (R2: 0.14 vs 0.04, p<0.001, Figure‐1). AD signature cortical thickness only modestly mediated the association between tau PET and MMSE scores over time in amyloid‐β+ AD dementia (34.2%[95%CI: 16.8%‐59.0%] of the total effect, p<0.001) and in amyloid‐β+ MCI (11.6%[0‐25.0%], p=0.044), but not in amyloid‐β+ CU (p=0.848, Figure‐2). Age (T=‐2.24, p=0.025), but not sex (T=0.95, p=0.341) or APOE genotype (T=1.32, p=0.188), modified the association between baseline tau PET and cognitive change, such that older individuals showed faster cognitive decline at similar tau PET levels (Figure‐3). Most results were replicated in the [18F]RO948 PET cohort.ConclusionTau PET is a promising tool for predicting future cognitive change and could support the prognostic process in preclinical(i.e. amyloid‐β+ CU) and prodromal (i.e. amyloid‐β+ MCI) stages of Alzheimer’s disease.
Self‐reported history of estrogen hormone therapy differentiates rates of amyloid accumulation (PiB‐PET) relative to males: Findings from the Harvard Aging Brain Study
Authors: Rubinstein Zoe B. , Buckley Rachel F. , Scott Matthew R. , Manning Lyssa K. , Mayblyum Danielle V. , Thibault Emma G. , Jacobs Heidi I.L. , Farrell Michelle E. , Properzi Michael J. , Rabin Jennifer S. , Chhatwal Jasmeer P. , Lois Cristina , Rentz Dorene , Price Julie C. , Schultz Aaron P. , Sperling Reisa A. , Johnson Keith A. 
Published: February 2022

AbstractBackgroundWomen’s Health Initiative Memory Study (WHIMS) findings suggest that hormone therapy increases risk of dementia. Conversely, evidence from the Kronos Early Estrogen Prevention Study (KEEPS) implicates estrogen hormone therapy (HT) as protective against ß‐amyloid (Aß) burden. We sought to explore if self‐reported HT use is associated with rates of Aß accumulation in an observational sample of clinically‐unimpaired older adults.Method134 participants (Age=73yrs±5.8) underwent at least three timepoints of Pittsburgh compound‐B (PiB)‐PET scans over an average of 9.7 years. Longitudinal PiB‐PET was examined as aggregate neocortical DVR (composite reference region: whole cerebellum + eroded white matter). Concurrent with baseline PiB‐PET, female participants self‐reported if they ever took HT. Participants were thus identified as: females who never used HT (HT‐:n=36), females who have ever taken HT to any extent (HT+:n=42), and males (M:n=56). We examined the relationship between these three groups and longitudinal PiB‐PET using linear mixed models, adjusting for baseline age, and with random slopes and intercepts. Post‐hoc analyses adjusted for APOEε4 status and examined interactions between HT and baseline PiB‐PET on change in PiB‐PET from baseline.ResultWhile we found no significant sex (male/female) difference in PiB‐PET accumulation (t=1.5,p>0.05,Fig 1A), we observed significant HT group differences with HT‐ exhibiting approximately half the PiB‐PET rate of change than M (t=2.3,p=0.02) and HT+ (t=1.8,p=0.07; Fig 1B). There was no significant slope difference between M and HT+ (t=0.32,p=0.75). These differences survived after covarying for APOEε4. A three‐way interaction with baseline PiB‐PET revealed a greater slope difference between HT‐ and M (t=2.1,p=0.04) in those with higher baseline PiB‐PET relative to lower baseline PiB‐PET (Fig 2).ConclusionHT‐ showed significantly slower rates of Aß accumulation than males and a trend‐level slower rate compared to HT+; these differences appear heightened with greater baseline Aß burden. With similar ages across HT groups (p=0.20), these differences did not appear to be a function of chronological age. It remains unclear whether the introduction of estrogen, a mediating commonality, or collider bias is driving these results. Our findings, in conjunction with other studies, suggest the relationship between HT and Aß is complicated and necessitates examination of HT type and duration.
Preclinical Alzheimer disease pathology partially mediates the relationship between cortical thickness and cognitive control
Authors: McKay Nicole S. , Dincer Aylin , Mehrotra Vidushri , Aschenbrenner Andrew J. , Balota David A. , Hornbeck Russ C. , Morris John C. , Benzinger Tammie L.S. , Gordon Brian A. 
Published: February 2022

AbstractBackgroundPrevious research has shown that with age and disease, the integrity of grey matter structures decline. One such measure of grey matter integrity is cortical thickness, where lower values represent thinning of the cortical surface. Given that cognitive performance tends to decline with age, we were interested in investigating whether performance on attention‐based tasks was related to cortical thickness measured using magnetic resonance imaging (MRI) in an unimpaired older adult cohort. Further, although often unmeasured in studies of cognitive aging, many older adults will present with Alzheimer Disease (AD) pathologies such as beta‐amyloid (Aβ) deposition, despite being asymptomatic. Therefore, we were also interested in quantifying how much of the behavior‐structure relationship seen in older adult cohorts is driven by preclinical AD.Method511 cognitively unimpaired (CDR™=0) older adults (Age: M=68.2, SE=0.38) enrolled in studies at the Knight Alzheimer Disease Research Center, were included in these analyses. All participants completed an MRI and several cognitive assessments (Stroop, Simon, and CVOE); a subset of individuals (n=396) also underwent Aβ‐positron emission tomography (PET). A spatial cortical map highlighting regions where cortical thickness and cognition were related was created (Figure 1). This map was entered into subsequent analyses as our MRI variable. We used an established attentional control composite as our behavioral measure of interest. Linear models were conducted to elucidate the relationship between cortical thickness and cognition, and a mediation analysis was performed to examine whether Aβ deposition impacted this relationship.ResultUsing vertex‐wise general linear models, we found that reduced cortical thickness in temporal, medial‐ and lateral‐parietal, and dorsolateral prefrontal cortex, predicted worse performance on an attention task composite (Figure 2). Interestingly, mediation analysis showed that levels of Aβ partially account for the observed relationship between cortical thickness and attentional control (Figure 3).ConclusionThese results demonstrate that behavioral variability seen in older adult populations reflects corresponding changes in brain anatomy, specifically cortical thickness. Furthermore, our results support the hypothesis that preclinical AD, as measured by Aβ deposition, is partially driving what would otherwise be considered general aging in a cognitively normal older adult population.
Cognitive Health After MenoPause (CHAMP) Study: A study of the health of the cholinergic system and risk factors for future cognitive decline in postmenopausal women aged 50‐70
Authors: Conley Alexander C , Shokouhi Sepideh , Dumas Julie , Newhouse Paul A 
Published: February 2022

AbstractBackgroundMenopause is associated with changes in hormone balances, and also to cognition in some women. These changes have been proposed to lead to an increased risk of developing Alzheimer’s disease (AD). However, there is not a clear understanding of how these changes are linked to neurodegeneration. One theory of what may be driving cognitive changes may be linked to how estrogen depletion affects cholinergic system activity. Preclinical studies have shown that estrogen is necessary for normal cholinergic functioning and its withdrawal leads to cholinergic dysfunction and cognitive impairment. And previous studies in postmenopausal women have shown that anticholinergic blockade is effective at modulating activity when performing working memory tasks.MethodThe CHAMP study will determine whether menopause‐related cognitive changes correlate with both cholinergic functional integrity and established AD biomarkers in a sample of 120 healthy postmenopausal women aged 50‐70 years. Using an anticholinergic challenge model, this study will examine cognitive performance on memory tasks using fMRI. The present study will collect established AD biomarkers of amyloid and tau levels in both blood and CSF samples, as well as through amyloid PET imaging, and markers of neurodegeneration including medial temporal lobe volume through structure MRI. In addition, the study will also collect genomic markers of impairment, such as APOE and COMT genotypes.ResultWe predict that women with poor compensation following menopause will be more sensitive to anticholinergic blockade, and will show decreased working memory performance, reduced brain activation, and decreased basal forebrain cholinergic system volume.ConclusionIn addition, we predict that these cholinergic markers will also be related to menopausal factors associated with poor cognition and biomarkers that are related to AD.
The association of blood pressure variability with white matter integrity and cognitive impairment in cerebral amyloid angiopathy
Authors: Sveikata Lukas , Zotin Maria Clara Zanon , Schoemaker Dorothee , Perosa Valentina , Etherton Mark , Ma Yuan , Charidimou Andreas , Greenberg Steven M. , Viswanathan Anand 
Published: February 2022

AbstractBackgroundEmerging evidence suggests that blood pressure variability (BPV) may contribute to small vessel disease (SVD) progression and cognitive impairment beyond the deleterious effects of elevated blood pressure, but the mechanisms remain largely unknown. This study investigates if BPV is associated with white matter (WM) microstructural integrity and the slope of cognitive decline in elderly individuals with cerebral amyloid angiopathy (CAA), a well characterized type of SVD.MethodWe recruited 94 non‐demented individuals (73.3 ± 7.0 y, 40 F, MMSE 27.7 ± 1.5) from a memory‐clinic cohort with and without possible/probable CAA with available neuropsychological evaluation and 3.0 T research MRI. Visit‐to‐visit BPV was assessed using the coefficient of variation derived from the serial outpatient BP measures during a 5‐year interval. A novel diffusion tensor imaging marker – peak width of skeletonized mean diffusivity (PSMD) – was used to evaluate the WM integrity. Using linear regression models, we evaluated the association of PSMD with BPV, adjusted for standard cardiovascular risk factors.ResultWe found a significant association between loss of WM integrity and high systolic BPV (β = 0.37, P < 0.001), but not mean BP. The association remained significant after adjusting for age, antihypertensive medication usage, diabetes, smoking, and body mass index. Furthermore, the association of BPV with WM integrity was stronger when CAA was present (P for interaction = 0.018). Higher BPV at baseline was associated with worse executive function in CAA patients at 2‐year follow‐up (β = ‐0.53, P = 0.003), adjusted for baseline function.ConclusionOur findings show that visit‐to‐visit BP fluctuations are associated with loss of WM microstructural integrity and cognitive decline. The association between BP variability and WM integrity might in part be driven by CAA pathology. Further studies are warranted to disentangle the relationship between BP fluctuations, microvascular injury, and cognitive impairment in older adults.
Sequential early cognitive changes sensitive to rising beta‐amyloid and tau pathology in preclinical AD
Authors: Farrell Michelle E. , Papp Kate V. , Buckley Rachel F. , Jacobs Heidi I.L. , Schultz Aaron P , Properzi Michael J , Vannini Patrizia , Hanseeuw Bernard , Rentz Dorene M. , Johnson Keith A. , Sperling Reisa A. 
Published: February 2022

AbstractBackgroundAD clinical trials are increasingly looking towards intervention at the earliest stage of preclinical AD, when beta‐amyloid (Aβ) is emerging and tau pathology remains restricted to the MTL. While some evidence suggests subtle cognitive changes start at this early stage, it is unclear what cognitive measures may be most sensitive to emerging pathology and whether they reflect Aβ, tau or both.Method143 clinically‐normal adults with longitudinal PIB‐PET, FTP‐PET and cognitive data (median follow‐up: 7.68(1.17) years) were included from the Harvard Aging Brain Study (HABS). Analyses focused first on those initially PIB‐ (<Centiloid (CL) 20), then were expanded to those initially <CL 40, approximately where neocortical tau proliferation accelerates. Linear mixed effects (LME) models first assessed the neocortical PIB slope*time effect on each cognitive task across the full time‐course. FTP was introduced later (∼Year 3), so LME models assessing combined PIB+FTP effects on cognition (Year3+) were divided into prior effects (PIB slope‐Year0‐3, Year3‐FTP level) and concurrent effects (PIB slope‐Y3+, FTP slope‐Y3+). Both entorhinal (ERC) and inferior temporal (IT) FTP were tested. ROC curve analyses assessed sensitivity/specificity of each task and composite measures to PIB slope.ResultIn PIB slope models across the full time‐course (Fig 1), rising PIB was robustly associated with declining processing speed (DSST, Trails A) in those <CL20 and expanded to include memory encoding (FCsrt‐FR, SRT‐tr, LM‐immed) in the <CL40 group. In the combined PIB+FTP models under CL20 (Fig 2), rising PIB slope associated with declining DSST, FCsrt‐FR, and SRT‐tr, while the only FTP effect was between rising ERC FTP and declining FCsrt‐FR. Expanding up to CL40, IT FTP became dominant and related to most cognitive tasks, but independent effects of PIB slope remained for DSST and the encoding measures. A composite measure (DSST, Trails A, FCsrt‐FR, LM‐immed) demonstrated high sensitivity and specificity (SE=.85, SP=.88, Fig 3) to PIB slope, performing better than any individual task and the PACC.ConclusionMeasures of processing speed and memory encoding were most sensitive to emerging Aβ and tau pathology, and may help to determine whether anti‐Aβ therapies administered at the first signs of Aβ and tau might preserve cognitive function.
Abnormal metabolic brain network in behavioral variant of frontotemporal dementia
Authors: Rus Tomaž , Ležaić Luka , Emeršič Andreja , Kramberger Milica G. , Pirtošek Zvezdan , Eidelberg David , Trost Maja 
Published: February 2022

AbstractBackgroundThe increasing number of patients with neurodegenerative dementia is a major public health issue. While clinical features of neurodegenerative disorders causing dementia are overlapping, accurate diagnosis is a prerequisite for an effective drug development. Besides the need for a better biomarker of Alzheimer’s disease (AD), development of non‐AD biomarkers is necessary. Behavioral variant of frontotemporal dementia (bvFTD) is the second most common neurodegenerative dementia in patients younger than 65 years. The aim of our study was to identify and validate bvFTD specific metabolic brain pattern using voxel‐based spatial covariance analysis according to the scaled subprofile model (SSM/PCA) on a new cohort of European patients and to study its biologic significance.Method20 patients with clinical diagnosis of bvFTD and 20 age‐matched normal controls (NC) underwent metabolic imaging with FDG PET. CSF results were available for 10/20 bvFTD patients and potential AD was excluded based on the biomarker profile. Using SSM/PCA, we identified a significant bvFTD‐related metabolic pattern termed bFDRP‐Slov. The stability of voxel weights on this pattern was evaluated using bootstrap resampling. For validation, pattern expression values were computed in an independent testing set comprised of 25 bvFTD and 22 NC subjects. The specificity of the pattern for bvFTD was assessed by computing values in patients with other causes of dementia: 26 with AD and 16 with sporadic Creutzfeldt‐Jakob disease (sCJD). bFDRP expression was correlated with disease duration and with MMSE.ResultThe bFDRP was characterized by pronounced metabolic reduction in the medial frontal cortex, middle and inferior frontal gyri, anterior cingulum, insula, bilateral caudate and thalamus. bvFDRP expression values discriminated bvFTD patients from their counterparts with AD, sCJD and NC (p<0.0001; one‐way ANOVA). The expression of this pattern was abnormally elevated in bvFTD patients in the identification and validation cohorts (p<0.0001). bvFTD patients’ pattern expression of values did not correlate disease duration or MMSE.ConclusionbFDRP is a promising metabolic network biomarker of the disorder, consistent with previously identified disease pattern. Further research is needed to study its clinical significance. Identification of multiple neurodegenerative brain networks may be critical as the combination of different patterns can improve diagnostic accuracy.