bluuebunny/crossref_metadata_2025_split huggingface dataset:
18F‐Flortaucipir PET imaging compared with autopsy in a clinically and pathologically heterogeneous group of patients with neurodegenerative dementias
Authors: McGinnis Scott M. , Touroutoglou Alexandra , Eckbo Ryan , Brickhouse Michael , Quimby Megan , Wong Bonnie , Frosch Matthew P. , Gomperts Stephen , Johnson Keith A. , Dickerson Brad C. 
Published: February 2022

AbstractBackgroundWe aimed to investigate the utility of qualitative visual rating of 18F‐flortaucipir tau (FTP) PET to predict the neuropathologic diagnosis in patients with a diverse array of clinical syndromes who were followed to autopsy.MethodFTP PET, PiB PET, and high resolution T1 MRI scans were rated independently by visual inspection by two raters blinded to clinical diagnosis in n=22 subjects, including patients with a clinical syndrome of amnesic dementia (n=1), posterior cortical atrophy (n=2), logopenic primary progressive aphasia (n=1), nonfluent PPA (n=4), semantic PPA (n=3), corticobasal syndrome (n=1), behavioral variant frontotemporal dementia with a MAPT mutation (n=3) or GRN mutation or C9orf72 expansion (n=2), progressive supranuclear palsy (n=4), or dementia with Lewy bodies (DLB; n=1). FTP scans were classified using a two‐tiered system. First‐tier classification distinguished scans as either “abnormal‐>high‐confidence AD,” “abnormal‐>mildly‐elevated uptake,” or “normal.” Among scans classified as “abnormal‐>high‐confidence AD,” second‐tier classification distinguished “typical AD,” “atypical AD,” or “late‐stage AD.” Among scans classified as “abnormal‐>mildly‐elevated uptake,” second‐tier classification distinguished “possible early‐stage AD,” “possible FTLD,” or “indeterminate.”ResultAll individuals with ADNC as the primary pathology were classified as abnormal‐>high confidence AD. All individuals with FTLD as the primary pathology were classified as abnormal‐>mildly‐elevated uptake‐>possible FTLD, but cases with FTLD‐TDP43 pathology were not distinguishable based on FTP from those with FTLD‐tau, supporting prior observations. Additional details will be reported on these and the other cases.ConclusionIn a clinically and pathologically diverse sample of patients with neurodegenerative dementias, visual rating of FTP PET accurately differentiates AD from FTLD. FTP PET is not useful for the discrimination of FTLD‐tau vs. FTLD‐TDP43.
Quantifying acute tau inoculations in living rats using PET
Authors: Kunach Peter 
Published: February 2022

AbstractBackgroundMonitoring tau propagation in the living brain has important pathophysiological and therapeutic implications. As tau imaging agents are dependent on tau conformations, we aimed to determine the tau species amenable to in vivo imaging. Previously we demonstrated that ex vivo tau preparations may be used to image tau seeds in living murine systems, as opposed to recombinant preparations. As such, the goal of this work is to examine the dose‐dependent relationship of patient derived AD‐tau fibrils on PET imaging outcomes.MethodA total of two 15‐month‐old (2 wild‐type, one male and one female) rats were used. All animal had a baseline scan with [18F] MK6240 before the stereotaxic injections. We tested tau PHFs from AD brains using ultracentrifugation of sarkosyl‐insoluble brain fractions. AD‐tau preparations were stereotaxically injected in the dorsal hippocampus. We tested injection volumes of 1 and 3 uL of equal concentrations (80 ng/uL). Contralateral hemispheres were injected with equivalent amounts of PBS, the solvent for tau preparations. All PET images were coregistered to the Waxholm Space Atlas of the Sprague Dawley Rat Brain sMRI using a linear transformation. The non‐displaceable binding potential (BPND) images were generated using cerebellar grey as a reference region based on Simplified Reference Tissue Method (SRTM).ResultInjection of sarkosyl‐insoluble brain fractions from AD patients displayed positive BPnd outcome in both volumes tested. Control hemispheres injected with PBS showed potential off‐target binding. Reliability of this outcome was investigated using peak normalized TACs. Hemispheres receiving AD‐tau injections showed visible divergence in retention, as compared to baseline. The hemisphere that was inoculated with 3uL of AD‐tau showed separation during washout. A similar effect was seen in the control hemisphere.ConclusionThese results continue to suggest ex vivo tau preparations may be used to image tau seeds in living murine systems. The reliability of PET and kinetic outcomes are dependent on the volume injected. Further investigation will aim to evaluate AD‐tau concentration as the dosage variable instead of injection volume. Cerebellar tissue from patients used to extract AD‐tau species should be as a control injection to account for the reagents used for protein extraction, instead of PBS alone.
Efficacy of a timed activity intervention in improving sleep and well–being: Findings from the Healthy Patterns trial
Authors: Hodgson Nancy A , Talwar Sonia , Aryal Subhash 
Published: February 2022

AbstractBackgroundIrregular sleep‐wake patterns are common in persons living with dementia, pose a great burden to caregivers, and are the principal causes of distress and institutionalization. A growing body of research supports the importance of activity‐based interventions to reduce the frequency and intensity of sleep wake disruption, enhance personhood and dignity, and improve quality of life (QOL).MethodA two‐arm RCT was conducted with 170 dyads of persons living at home with dementia and with symptoms of sleep‐wake disruption, and their family caregiver. Specific components of the Healthy Patterns intervention include: 1) assessing health/functional status and preferences/interests; 2) educating caregivers on environmental cues to promote activity and sleep; and 3) training caregivers in using timed morning, afternoon, and evening activities based on circadian needs. Outcomes included: QOL, function, neuropsychiatric symptoms, and actigraphic and proxy‐reported measures of sleep‐wake patterns.ResultAt 4 weeks, the intervention group showed significantly greater improvement than the control group in QOL (p=.01) and sleep efficiency (p=.04).ConclusionResults provide new fundamental knowledge regarding the nature and timing of activities for persons with dementia. It has the potential to change how and when activities for persons with dementia are provided.
Cortical gray matter volume and working memory in a NHP model of AD‐like neuropathology
Authors: Frye Brett M. , Craft Suzanne , Register Thomas C. , Kim Jeongchul , Whitlow Christopher T. , Barcus Richard A. , Lockhart Samuel N. , Solingapuram Sai Kiran K. , Shively Carol A. 
Published: February 2022

AbstractBackgroundAge‐related neurodegeneration characteristic of late‐onset Alzheimer’s disease (LOAD) begins in middle age, well before symptoms. Therefore, translational models to identify modifiable risk factors in middle‐age are needed to understand the etiology and identify early therapeutic targets for intervention. Vervet monkeys (Chlorocebus aethiops sabaeus), like humans, have complex central nervous systems and naturally develop several risk factors for LOAD with age, including obesity, prediabetes, hypertension and decline in physical function. Furthermore, aged vervets also recapitulate many of the characteristics of early AD that are associated with reduced brain volumes, including human‐like Aβ accumulation in the brain, greater Aβ plaque burden, and reduced CSF Aβ. Thus, these NHPs are ideal models for studying healthy versus neuropathological aging.MethodUsing structural magnetic resonance imaging and cognitive assessments, we examined the relationships between age, working memory, and neuroanatomy by measuring the thicknesses and volumes of AD‐signature cortical regions of interest (“meta‐ROIs”) in 46 middle‐aged to elderly female vervets (8‐29 years of age).ResultUsing linear mixed effects models with age as a fixed effect and individual as a random effect, we found that cortical gray matter volume significantly decreased with increasing age (β=‐51.94, SE=14.37; t=‐3.61; p<0.001). The thickness of the AD‐signature meta‐ROIs was not affected by age (β<0.01, SE<0.01; t=‐0.19; p=0.85), however, the volumetric meta‐ROI tended to decline with age in older animals (β=‐6.95, SE= 4.20; t=‐1.65; p= 0.098). In the precuneus, a component region of the meta‐ROI that has been shown to be reduced in preclinical AD, volume decreased with increasing age (β=‐1.69, SE=0.72; t=‐2.36; p= 0.023). In addition to these age‐related effects, the volume of the AD‐signature meta‐ROI was positively correlated with performance on the delayed response test of working memory (R= 0.235; p=0.026).ConclusionTaken together, these findings demonstrate that cortical gray matter diminishes with age in vervet monkeys in regions relevant to AD risk, and is associated with cognitive impairment. This study provides important insights about the relationships between age, neuroanatomy, and memory in vervets, and lays the groundwork for future investigations to identify at‐risk phenotypes such that therapeutic interventions may be tested in this nonhuman primate model.
Locus coeruleus integrity as a proxy of initial tau burden: in vivo versus ex vivo observations
Authors: Jacobs Heidi I.L. , Becker Alex , Kwong Kenneth , Engels Nina , Prokopiou Prokopis C. , Papp Kate V. , Properzi Michael J , Hampton Olivia L. , Sanchez Justin S. , Rentz Dorene M. , Fakhri Georges El , Normandin Marc D. , Bennett David A. , Sperling Reisa A. , Johnson Keith A. 
Published: February 2022

AbstractBackgroundAutopsy studies reported the locus coeruleus (LC) as one of the initial regions in the brain harboring hyperphosphorylated tau pathology. MR signal intensity in the LC has been proposed as a measure of LC integrity, but the contribution of tau pathology, commonly found in LC, to this signal intensity is not currently measurable in vivo. We related in‐vivo LC MR signal intensity to Alzheimer’s disease (AD) phenotype and PET measures and used ROSMAP autopsy data to guide interpretation of the MR LC measure as tau‐related or cellular integrity‐related.MethodOne‐hundred seventy‐two participants from the Harvard Aging Brain Study (HABS) underwent 3T LC‐MRI imaging, FTP and PiB‐PET imaging (median age: 75 years, 58% female, n=22 with CDR=0.5/1). In 160 individuals from ROSMAP, LC tangle density and neuronal density were quantified at autopsy (median age at death: 89 years, 67% female, 66 control, 53 mild cognitively impaired, 41 AD patients; Figure 1). Groups were compared using ANCOVA. LC measures were related to Mini‐Mental State Examination (MMSE) scores using Spearman correlations (age‐adjusted). In HABS, LC integrity was vertex‐wise regressed on tau‐PET. In ROSMAP, Spearman correlations related LC tangle or neuronal density to cortical tangle density or Braak staging.ResultLC measures correlated with measures of disease progression: in HABS, LC integrity was lower in impaired individuals compared to controls, and correlated positively with MMSE score. In ROSMAP, LC tangle density was higher in MCI/AD patients compared to controls; and correlated negatively with MMSE scores. No associations were found for LC neuronal density (Figure 2). Furthermore, lower LC integrity correlated with higher tau in medial‐lateral temporal regions in HABS, mirroring the consecutive Braak‐staging. Similarly, In ROSMAP, higher LC tangle density, but not LC neuronal density, correlated positively with cortical tangle burden and Braak staging (Figure 3).ConclusionThe comparable associations of MRI‐LC integrity or LC tangle density with disease progression and tau suggest that MRI‐measures of LC integrity may be a proxy for tau pathology, rather than neuronal density. Future verification using head‐to‐head comparison is warranted, but our results indicate that LC integrity holds promise as marker for detection of initial AD‐related processes.
The logistical landscape of lay dementia care
Authors: Reilly Shannon , Manning Carol A 
Published: February 2022

AbstractBackgroundIn 2018, more than 16 million unpaid caregivers (CG) provided care for people with dementia (PWD), care that is associated with increased caregiver depression, poor health and caregiver burden (Alzheimer’s Association, 2019). This observational, cross‐sectional study examined CGs’ relationships to PWDs, how CGs allot their caregiving time, how caregiving affects their work, and CGs’ mental health. We hypothesized that CGs would be primarily spouses or children of the PWD, that they would provide the majority of unpaid care without an extensive support system and with a significant amount of time spent on caregiving, that would disrupt their employment, and be accompanied by relatively high levels of mental health symptoms.MethodAt the initiation of a dementia care coordination program, CGs (N = 96) were surveyed regarding their personal characteristics, the PWDs they care for (N = 96), and CG perceptions of caregiving. Descriptive information about the landscape of their caregiving at baseline is presented (Table 1).ResultMost CGs were women, whereas PWD gender was more evenly split. Most CGs were spouses or children of PWDs, and over 70% lived with the PWD. Only about half were the PWD’s power of attorney. The majority of CGs provided over 80% of care to the PWD, often unpaid and without other help. On average, CGs spent the equivalent of a full‐time job supervising and assisting with complex activities of daily living (ADLs) and the equivalent of a part‐time job assisting with basic ADLs. Of employed CGs (<50%), over 85% were not paid for caregiving, and caregiving disrupted their work. CGs on average had a clinical degree of depression, minimal anxiety, and mild to moderate caregiver burden.ConclusionThis sample of CGs is generally consistent with our expectations and national U.S. statistics on CGs (e.g., Alzheimer’s Association, 2019). Importantly, CGs spend large amounts of time providing unpaid caregiving with significant financial consequences and little support from others. CGs are a vulnerable group in terms relatively high levels of depression and CG burden. Innovations in provision of caregiver support are needed to help this vulnerable but growing population.
Lower regional cerebrovascular reactivity relates to worse episodic memory among older adults
Authors: Robb W. Hudson , Ahmed Humza A. , Kim Darcie S. , Landman Bennett A. , Pechman Kimberly R. , Gifford Katherine A. , Donahue Manus J. , Hohman Timothy J. , Jefferson Angela L. 
Published: February 2022

AbstractBackgroundCerebrovascular reactivity (CVR) measures the ability of the cerebrovasculature to respond to vasoactive stimuli. Decreased CVR in the default mode network (DMN) has been associated with increased vascular risk factor burden. DMN connectivity is fundamentally dependent on vascular compliance, which can be altered in MCI, and may impact episodic memory consolidation. This study cross‐sectionally evaluated whether the topography of CVR is associated with episodic memory performance.MethodVanderbilt Memory & Aging Project participants free of stroke were included (n=117, 76.0±7.3 years, 46% female). Participants underwent neuropsychological assessment and multimodal 3T brain MRI, including T1‐weighted imaging and T2*‐weighted blood‐oxygenation level‐dependent (BOLD‐fMRI) for quantifying CVR. During the BOLD‐fMRI acquisition, a hypercapnic normoxic respiratory challenge was administered by alternating normocapnic normoxia and hypercapnic normoxia (5% CO2/95%‐air) in 90s blocks. BOLD‐fMRI data were time‐delay processed, yielding whole‐brain mapping of the maximum correlation with the gas stimulus (CVRMAX) and time‐to‐max CVR (CVRDELAY). Mean CVR metrics were calculated in atlas‐derived DMN regions. Ordinary least squares regression models related DMN‐CVR to episodic memory performance adjusting for demographics, Framingham Stroke Risk Profile, and apolipoprotein E‐e4 status. Clusters were corrected using family‐wise‐error rate p<0.05.ResultDMN‐CVRMAX was related to episodic memory performance (b=1.0x10‐3, p=0.03) but DMN‐CVRDELAY was not (p=0.09). In voxelwise analysis relating CVRMAX to memory, seven clusters surviving correction were identified, all suggesting lower CVRMAX related to worse memory performance. The peak value of the top cluster was located in the middle temporal gyrus. In voxelwise analysis relating CVRDELAY to memory, 11 clusters surviving correction were identified, all indicating longer CVRDELAY related to worse memory performance. The peak value of the top cluster was located in postcentral gyrus.ConclusionAmong older adults, lower DMN‐CVRMAX is associated with worse episodic memory performance and this association is not confined to the DMN. Associations between regionally reduced vascular compliance and episodic memory may result from vascular impairment of large‐scale brain networks such as the DMN, though these associations should be further explored. T32‐AG058524, IIRG‐08‐88733, R01‐AG034962, R01‐NS100980, K24‐AG046373, P20‐AG068082
Analysis of clinical and sociodemographic factors involved in older adults' cognition
Authors: Pires Lívia R , Costa Mônica Vieira , de Oliveira Hansen Erika , Pires Ricardo Lage Guerra Lott , FARIA KAREN C , Dias Bruna Fugêncio , Braga Nayara Rodrigues , Ávila Rafaela , Bertola Laiss , Bicalho Maria Aparecida C 
Published: February 2022

AbstractBackgroundElderly population is rising significantly in Brazil. It may reach 25.5% of the population by 2060. Cognitive and functional declines may happen during pathological aging process. Low and medium‐income countries tend to present higher dementia growth rate than high‐income countries. The aim of this study was to assess whether socio‐demographic and economic indicators are associated with cognitive performance in older adults with normal cognition and with mild cognitive impairment (MCI).MethodWe conducted a transversal study enrolling 69 Brazilian older adults from the outpatient Reference Center for the Elderly of Belo Horizonte ‐ Federal University of Minas Gerais. We included participants with MCI and without cognitive and functional impairment (control group‐NC). All participants were submitted to the same protocol. Sociodemographic and clinical variables were evaluated by self report and medical records. Neuropsychological assessment consisted by the Geriatric Depressive Scale (GDS), Pfeffer Instrumental Daily Living Activities scale (FAQ), Mattis Dementia Rating Scale (DRS), Frontal Assessment Battery (FAB) and Wechsler Abbreviated Scale of Intelligence (WASI). We used linear regression to analyze relationship between sociodemographic factors and ageing cognition.Result69 older adults, 69.6% women, average age of 76.58 (SD ±5.43) years, 4.55 (SD ±3.39) years of formal education were included in our study. Correlation analysis demonstrated that Diabetes Mellitus correlated with memory performance (M). Intelligence quotient (IQ) were associated with executive functions (EF), attention and conceptual abilities (C); years of formal education presented significant association with general cognitive measures (GC); socioeconomical level was associated with GC, EF, attention, construction and conceptualization; parents’ education positively correlated with visuoconstruction and, Occupational level had positive association with GC, attention and conceptualization. Regression analysis indicated IQ level predicts EF and GC in adult life. Education predicted GC, EF, memory and conceptualization. Education also showed a tendency to explain the attention domain.ConclusionOur results suggest sociodemographic factors, such as IQ, education, sociodemographic level, parents’ education and occupational level associate with cognitive abilities. They could act as protection factors for the cognitive decline in elderly. Prospective studies, with larger samples, are needed to evaluate if these factors are able to reduce dementia risk in elderly population of low educational level.
Protective factors associated with mental health symptoms in caregivers of persons with dementia
Authors: Reilly Shannon , Manning Carol A 
Published: February 2022

AbstractBackgroundCaregivers (CGs) of persons with dementia (PWDs) have relatively high levels of caregiver burden, depression, and anxiety. This observational, cross‐sectional study examined the extent to which preparedness for caregiving and knowledge about dementia might be associated with lower levels of these mental health symptoms.MethodAt the entry into a dementia care coordination program, CGs (N = 74) were surveyed about personal characteristics, characteristics of the PWD they care for (N = 74), mental health symptoms, and their perceptions about caregiving. Three univariate linear regressions were conducted to assess associations between protective factors (i.e., preparedness for caregiving, dementia knowledge) and CGs’ levels of depression, anxiety, and caregiver burden, controlling for CG age, CG education, and PWD level of functional independence in activities of daily living (ADLs).Result(Table 1). Neither preparedness for caregiving or dementia knowledge were significantly associated with CG depression or anxiety. However, younger CGs reported higher levels of depression (B = ‐.007, t = ‐3.33, p = 0.001) and anxiety (B = ‐.12, t = ‐2.91, p = 0.005). CGs with higher preparedness for caregiving reported lower CG burden (B = ‐.67, t = ‐2.51, p = 0.015), and CGs of PWDs with lower functional independence reported higher CG burden (B = ‐2.19, t = ‐2.96, p = 0.004).ConclusionResults of this cross‐sectional, observational study indicate that CGs’ preparedness for caregiving is associated with CG burden and that younger GGs had higher levels of depression and anxiety. These findings suggest that CG age may impact CG mental health and provide opportunities for intervention including targeting mood in younger CGs and increasing CG preparedness to potentially decrease CG burden. Additionally, emotional preparation for providing care to PWDs may be more important for reducing CGs’ burden than teaching specific knowledge about what to expect in dementia, and CGs of PWDs with lower functional abilities may benefit from targeted supports to reduce burden.