bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ventricle shape features as a reliable differentiator between the behavioral variant frontotemporal dementia and other dementias
Authors: Manera Ana Laura , Dadar Mahsa , Collins Louis , Ducharme Simon 
Published: February 2022

AbstractBackgroundIn the absence of a pathologic genetic mutation, diagnostic certainty of the behavioral variant frontotemporal dementia (bvFTD) still relies on convergence of clinical criteria and imaging findings. Using deformation‐based morphometry (DBM), we recently showed that ventricular volume can discriminate bvFTD from cognitively normal controls (CN)1. Here, we investigate the performance of shape‐based ventricular features to differentiate bvFTD from Alzheimer’s Dementia (AD), mild cognitive impairment (MCI), semantic and progressive non‐fluent aphasia variants of FTD (SV and PNFA), and CN.MethodData included 825 participants: 59 bvFTD, 28 SV, 30 PNFA, and 105 CN from the Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) and 322 age‐matched amyloid β+ MCI, 127 age‐matched amyloid β+ AD and 164 age‐matched CN from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). A previously validated patch‐based label fusion technique was employed to segment the lateral ventricles 2. Linearly registering the images to ICBM2009c template, the ventricles were divided into anterior‐posterior (using coronal slice y=120) and left‐right halves (separately for frontal and temporal lobes). Total ventricle volume (TVV), anterior‐to‐posterior ratio (APR) and frontal and temporal parenchymal left‐right ratios (LRFR and LRTR) were used alone and in combination with each other, age, and sex, to differentiate bvFTD from all other cohorts. A support vector machine classifier (fitcsvm from MATLAB with a linear kernel) was trained on each feature set to perform the classification task using 10‐fold cross validation, repeated 100 times.ResultUsing APR to identify bvFTD from a mixed age‐matched cohort (Control, MCI, AD, SV and PNFA) yielded an accuracy of 92%. Adding additional features did not improve global classification performances. The top accuracies against each individual cohort were 89% for bvFTD vs Control, 91% for bvFTD vs MCI using APR+TVV, and 83% for bvFTD vs AD using APR+LRTR. The best accuracies discriminating bvFTD from SV and PNFA were 71% and 76% respectively, using APR+TVV+LRTR+LRFR.ConclusionThe APR is an easy to obtain and generalizable ventricle‐based feature from T1‐weighted MRIs (routinely acquired and available in the clinic) that can be used to differentiate bvFTD from normal subjects, other FTD variants, MCI, and AD patients.
Dementia care in diverse older adults in the Deep South and the rest of the United States
Authors: Pisu Maria , Martin Roy C , Shan Liang , Pilonieta Giovanna , Kennedy Richard E , Oates Gabriela , Kim Young‐Il , Geldmacher David S 
Published: February 2022

AbstractBackgroundPrevalence of Alzheimer’s disease and related dementia (ADRD) is increasing especially in the southeastern US. For older adults with ADRD, gaps exist in utilization of specialists (neurologists, psychiatrists, geriatricians) and ADRD drugs, e.g., across racial/ethnic (R/E) patient groups. Because some R/E groups, e.g., African Americans (AAs), are overrepresented in the Southeast, closer scrutiny of their ADRD care is needed. Within the Southeast, the Deep South (DS) includes some of the poorest US states (Alabama, Mississippi, Louisiana, Georgia, and South Carolina). We examined R/E disparities in specialist and drug utilization in DS vs. non‐DS states, and examined individual and context‐level factors that impact utilization in each region.MethodsPopulation, outcomes, and individual‐level covariates were identified from claims for fee‐for service Part A/B (hospital, outpatient) and D (prescription drugs) Medicare beneficiaries in 2013‐2015 (66 and older). For context‐level covariates, we combined Area Health Resource File county‐level data in exploratory factor analysis (EFA). We conducted adjusted analyses for DS and non‐DS with outcomes: 1) ≥ 1 specialist visit; and 2) ≥ 1 prescription for donepezil, galantamine, rivastigmine, or memantine. R/E groups included AAs, Non‐Hispanic Whites, Hispanic, Asian/Pacific Islander, and Other.ResultsWe identified 127,512 Medicare beneficiaries with ADRD (9.4% in DS). Specialist utilization ranged from 37% AAs to 42% Whites in DS, 45% Whites to 50% AAs in non‐DS. ADRD drug utilization ranged from 48% AAs to 55% Hispanics in DS, 42% AAs to 48% Hispanics in non‐DS. EFA identified 4 context‐level factors with two common to DS and non‐DS. R/E disparities were not significant, except for non‐DS Asian/Pacific Islanders vs. Whites (RR 0.81, CI = 0.777‐0.849, p<.0001). In DS and non‐DS, comorbidities, poverty, and EFA factor “Medical Resources Availability” were associated with utilization outcomes. No other factor was associated with outcomes in DS. In non‐DS, factors “Population Health”, “Health Insurance Market” were associated with outcomes.ConclusionADRD specialist and drug utilization is relatively low in both DS and non‐DS, with no significant R/E differences. Research should continue to examine factors that may drive medical care decisions of older adults with ADRD in US regions with different socio‐economic and medical resource contexts.
Automated delineation of enlarged perivascular spaces (EPVS)
Authors: Goryawala Mohammed , Del Brutto Andrade Victor , Saporta Anita Seixas Dias , Loewenstein David , Rundek Tatjana 
Published: February 2022

AbstractBackgroundEnlarged Perivascular Spaces (EPVS) are associated with small vessel disease. The objective of this study was to develop semi‐automated techniques for the quantification of EPVS burden.MethodAn intensity‐based threshold was used to identify EPVS. A threshold of maximum plus two standard deviations of intensities of normal‐appearing white matter in the supratentorial region was used to identify EPVS. To compare the performance of the semi‐automatic approach for EPVS segmentation to visually rated EPVS scores, two regions of interest were outlined in the basal ganglia (BG) region and the centrum semiovale (CS). For both these regions, a score was generated by an experienced neurologist by visually counting the number of EPVS with a score of zero representing the absence of any EPVS, a score of 1 representing 1‐10 EPVS, a score of 2 representing 11‐20 EPVS, a score of 3 representing 21‐40 EPVS, and a score of 4 representing >40 EPVS. The semi‐automatic approach provided a count of the number of EPVS that were converted to grade using the same scaling as the visual approach. Spearman Rank Order Correlation Coefficient was calculated to estimate the correlation between the two methods. Mann‐Whitney U tests of ranks are employed to determine if any group differences are present. Finally, Cohen’s kappa was used to compare the concordance between measures between the two different methods.ResultFigure 2 shows the results of the segmentation in subjects with differing EPVS burden. Spearman Rank Order Correlation analysis showed a significant correlation between the EPVS scores determined visually and those obtained semi‐automatically in 60 subjects (Table 1). Results of the Mann‐Whitney U tests showed that there was no statistically significant (p > 0.05) difference between the EPVS scores obtained visually and using the semi‐automatic approach (Table 2). Cohen's κ test showed that there was moderate agreement between the two estimation methods in the BG (κ = .522, p < .0001) and CS regions (κ = .571, p < .0001).ConclusionThe developed method showed good concordance with expert visual read and can provide quantitative measures of EPVS burden (counts and volume) for evaluation of vascular risk.
The plasma fraction GRF6019 slows brain atrophy in mild‐to‐moderate Alzheimer’s disease
Authors: Lehallier Benoit , Lohr Scott , Braithwaite Steven P. , Hannestad Jonas 
Published: February 2022

AbstractBackgroundThe plasma fraction GRF6019 shows multiple benefits on age‐related changes in the mouse brain, including enhanced synaptic density and neurogenesis. In a trial of GRF6019 in mild‐to‐moderate Alzheimer’s disease (AD), cognition stabilized over a 24‐week period (Hannestad et al., 2020). Here we present the volumetric MRI data from that trial.MethodParticipants were 60‐90 years old with probable AD according to NIA‐AA criteria, and Mini Mental State Examination score 12‐24. They received 1 daily infusion of 100 mL or 250 mL of GRF6019 over 5 consecutive days at Week 1 and Week 13. MRIs were done at baseline at the end of the study using a MP‐RAGE or IR‐SPGR sequence. The 3D T1‐weighted scans were acquired sagittally over approximately 192 slices at a thickness of 1.0‐1.2. Images underwent the Freesurfer pipeline and hand editing to correct over‐ and under‐estimations of hippocampal volumes. Hippocampal and lateral ventricular volumes were extracted and normalized by the estimated total intracranial volume. Fold‐changes between baseline and 6 months were estimated and log2‐transformed to obtain a symmetrical distribution. MRI images from ADNI were analyzed in the same manner.ResultHippocampal volumes decreased from baseline by 2% (p<0.001, one‐sample Wilcoxon test) in ADNI AD participants (n=75), while hippocampal volumes did not significantly change in ADNI control participants (n=82; 0.03%, p>0.05) or in GRF6019‐treated AD trial participants (n=34; 0.3%, p>0.05). Lateral ventricle volumes increased from baseline by 5.2% in ADNI AD but showed smaller increases in ADNI controls (2.7%) and in GRF6019‐treated individuals (3.1%). The difference in change from baseline between GRF6019 AD and ADNI AD was significant in the right lateral ventricle (p<0.005, two‐samples Wilcoxon test) but not in the left lateral ventricle. There was no apparent difference in the change from baseline in MRI volumes between the 100 ml and 250 mL dose of GRF6019.ConclusionIn mild‐to‐moderate AD, the plasma fraction GRF6019 slowed hippocampal atrophy and lateral ventricle enlargement compared to matched individuals with AD in ADNI. The MRI data are consistent with the lack of cognitive worsening observed in these trial participants and supports continued clinical development of GRF6019 in AD.
The preliminary efficacy of Caring of Caregivers Organically (CoCO) health education program on the health of Latina caregivers of persons with Alzheimer’s disease and related dementias
Authors: Guzman Jacqueline , Rocha Judith Susan , Soto Yuliana , Aguiñaga Susan 
Published: February 2022

AbstractBackgroundBy 2060, the prevalence of Alzheimer’s disease and related dementias (ADRD) in Latinos is projected to increase by 832%,1 representing an increased demand of caregivers. Caregiving has been shown to increase risk for depression and anxiety,2 poorer quality of life (QoL)3 and health behaviors.4 There is a critical need to create linguistically and culturally responsive interventions to promote caregiver health as they often forgo their own health to help the person with ADRD. CoCO is a health education program centered on caregiver’s physical and mental health. The purpose of this study was to assess the preliminary efficacy of CoCO on health‐related QoL, health behaviors, and symptoms of depression among Latina ADRD family caregivers.MethodsFourteen Latina ADRD family caregivers were randomized to the 8‐week, 2‐hours per week CoCO health education program delivered by health companions (n=8, mage=59.41±11.1) or a wait‐list control group who received the CoCO manual (n=6, mage=43.3±18.2). Health‐related QoL was assessed through the RAND 36‐item Health Survey (SF‐36).5 The Positive Health Behaviors scale6 was used to assess engagement in healthy activities. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale.7‐8 T‐tests were used to assess change in the measures per group pre‐post intervention. Cohen’s d was used to calculate effect sizes.ResultsThere were statistically significant increases in depressive symptoms pre‐post in both the intervention group (PreM=14.1±13.3, PostM=22.5±14.9, p=.007, d=1.32) and the control (PreM=5.5±3.6, PostM=14.0±10.0, p=.046, d=1.08). There were statically significant decreases in the emotional well‐being domain of the SF‐36 questionnaire in the control group only (PreM=79.3±18.5, PostM=67.3±15.5, p=.030, d=1.23). Cohen’s d values showed medium effect sizes showing a positive directionality in the physical activity domain of the health behavior scale for the intervention group only (PreM=5.50±4.90, PostM=7.75±4.03, p=.152, d=0.57).ConclusionParticipants in the intervention demonstrated medium effects for the physical activity domain, suggesting an increase in physical activity. However, findings also indicate increased depressive symptoms and poorer health‐related quality of life. Health education interventions promoting health behavior changes in Latina ADRD family caregivers might benefit from including more extensive problem solving and coping strategies to improve depressive symptoms and QoL.
Dementia, fall risk and routine clinical care: An opportunity to enhance care by incorporation of examiner independent computerized cognitive testing
Authors: Kaczmarek Olivia , Rosenfeld Yulia , Chee Jordan , Bumstead Barbara , Zarif Myassar , Anand Bhupinder , Ofori Edward , Gudesblatt Mark 
Published: February 2022

AbstractBackgroundDementia is an encompassing term referring to multiple clinical conditions characterized by progressive cognitive impairment (CI) that interferes with an individual’s ability to function independently. Clinically, CI varies in degree and combination of cognitive deficits from memory loss, verbal impairment, apraxia to impaired executive function. Clinician recognition of such varied types/degrees of CI is likely problematic. Falls are common and their consequence costly in individuals with such cognitive impairment. Effective analysis of multiple aspects of cognitive function can be provided in routine care with a validated, examiner independent, sensitive and reliable computerized cognitive assessment battery, (CAB, Neurotrax) which specifically evaluates multiple cognitive domains (CD): Memory (MEM), Executive Function (EXE), Visual Spatial (VIS), Verbal Function (VER), Attention (ATT), Information Processing (INF), and Motor Skills (MOT) and a Global Cognitive Summary Score (GCS).MethodCross sectional analysis of PwDaD who underwent standardized CAB cognitive testing and were also screened for risk of falls based on number of falls in the past and persons fear of falling.Result120 PwDaD, 57.5% female, average age 74 +/‐ 10 years. T‐tests were performed between CAB CD scores grouped by risk of falling (high/low). The following CD scores were associated with increased fall risk: GCS (p=<.05) and VIS (p=<.05). A significant increased fall risk was also associated with an accumulative CDI (# of individual cognitive domains impaired) (p=<.05).ConclusionAs CAB measured cognition decreases PwDaD risk of falling increases. PwDaD at increased risk for falls had increased accumulative CI with an average of 3 CDI. PwDaD also at increased risk for falls have significantly lower GCS and Visual Spatial scores. Earlier identification of increased fall risk might allow clinicians an opportunity to effectively and pre‐emptively intervene to reduce such increased disability consequence and costs associated with this disease related impact.
Qualitative study of frontotemporal lobar degeneration caregivers' coping strategies and concerns during COVID‐19
Authors: Martinez Maria , Tartaglia Maria Carmela , Cacchione Elena , Monteiro Marta , Maboudi Mehrdad , Ragnanan Tracey 
Published: February 2022

AbstractBackgroundThe coronavirus (COVID‐19) pandemic has been particularly arduous on those living with dementia and their caregivers as they depend on in‐person support and programs. High rates of depression and anxiety were reported in Alzheimer's disease during the COVID‐19 pandemic (El Haj, 2020). In patients with frontotemporal lobar degeneration (FTLD) there are additional challenges as these patients have motor, language, behavior disorders and cognitive deficits. We examined the impact of COVID‐19 on FTLD caregivers.MethodFrom March 2020‐June 2020, we carried out a qualitative study with FTLD caregivers to determine the impact of COVID‐19 on their continued ability to care for the person with dementia. We examined the following: patient’s age, relationship to primary caregiver, number of people in household, access to virtual telecommunication, access to exercise, caregivers’ greatest supports, their identified needs and fears.ResultWe included 52 FTLD patient‐caregiver dyads (5 behavioral variant (bvFTD), 17 primary progressive aphasia (PPA), 19 Corticobasal Syndrome (CBS), and 11 Progressive Supranuclear Palsy (PSP)). Mean age of patients was 67.9+/‐8.76. 57% of caregivers were female. 60% of patients lived alone with spouse, 23% lived with spouse and a child, 2 patients lived in LTC, 3 with a family member (not spouse) or friend, 1 was in hospital, and 2 lived alone. 75% had access to virtual telecommunication. 44% were engaged in physical activity (mostly walking). 16 caregivers (25%) reported their greatest needs were reinstating or increasing Personal Support Worker hours, 8 (15%) needed access to other health care providers and for 7 (13%) they wanted Adult Day Programs to reopen. 31 caregivers (60%) reported their greatest support was family; 8 (15%) were grateful for community supports. 22 caregivers (42%) were concerned about ongoing decline whilst only 11 (21%) feared COVID.ConclusionWe provide some qualitative data on FTLD caregivers’ experience during COVID. The most frequent concern was ongoing decline. Over 50% of caregivers reported their greatest need was access to services and their greatest support was family network. Enabling easily accessible and safe in‐home care is important to support people living at home with FTLD during the pandemic. REFERENCES: El Haj, M. Psychiatry Research, (2020).
Associations of hippocampal cholinergic receptor binding and subcortical cerebrovascular disease with whole brain volume in cognitive aging and AD
Authors: Lim Aaron C. , Sultzer David L , Gordon Hailey L. , Melrose Rebecca J. 
Published: February 2022

AbstractBackgroundAlzheimer’s Disease (AD) is associated with compromise to the cholinergic system. Using PET ligand imaging, our group has reported reduced nicotinic cholinergic receptors (nAchR) in the hippocampus in AD relative to cognitively unimpaired older adults. Studies have increasingly identified that chronic ischemic cerebrovascular disease (CVD) serves as a risk factor for neurodegeneration, and also directly correlates with B‐amyloid and tau accumulation (Flaherty et al., 2020; Wei et al., 2019). We sought to determine the unique contributions of cholinergic dysfunction and CVD to brain health in cognitive aging. We therefore tested differential contributions of T1 white matter hypointensities and hippocampal nAchR binding in predicting whole brain volume among individuals with varying levels of cognitive impairment.Method84 individuals (clinical Alzheimer’s Disease (AD), n=27; Mild Cognitive Impairment (MCI), n=25; and Cognitively Unimpaired (CU), n=32) completed MRI and 2‐18F‐fluoro‐3(2(S)azetidinylmethoxy) pyridine (2FA) ‐PET imaging sessions. Total Brain Volume, excluding cerebellum, brain stem, and ventricles, was calculated using FreeSurfer. SPM was used to generate nAchR binding estimates using anatomical ROI of bilateral hippocampus.ResultWhen covarying for diagnostic group, age, and use of cholinesterase inhibitors, hierarchical linear regressions identified a significant association between hippocampal nAchR binding and total brain volume (B(SE)=.013(.003); p<.001), while the association between white matter hypointensities and total brain volume was not significant (B(SE)=‐.99(.84); p=.24). Stratified by group, the same pattern emerged in a combined sample of clinical AD and MCI (nAchR binding B(SE)=.013(.005); p<.01, hypointensities B(SE)=‐.18(.91); p=.84). In CU, however, white matter hypointensities were negatively associated with total brain volume (B(SE)=‐10.60(3.53); p<.01), while the relationship between hippocampal nAchR binding and total brain volume was not significant (B(SE)=.006(.005); p=.26).ConclusionWhite matter hypointensities are associated with a measure of brain health among CU; such vascular risk factors may be important to track in preventative treatment. Hippocampal cholinergic function, relative to hypointensities, may be more closely aligned with brain health among those with cognitive decline. Longitudinal study of vascular and cholinergic systems and their interactions are warranted; corroboration of these findings in longitudinal studies may elucidate different treatment targets across stages of AD.
Racial differences in dementia‐related pathology underlying cognitive decline: The Multi‐Ethnic Study of Atherosclerosis (MESA)
Authors: Hughes Tim M. , Schaich Christopher L. , Lockhart Samuel N. , Hiatt Kevin , Whitlow Christopher T. , Jung Youngkyoo , Bertoni Alain , Burke Gregory L. , Solingapuram Sai Kiran K. , Heckbert Susan , Craft Suzanne , Rapp Stephen R. , Hayden Kathleen M. 
Published: February 2022

AbstractBackgroundRacial differences in dementia‐related pathology are purported to underlie health disparities in Alzheimer’s disease and related disorders. We examined the prevalence and relevance of neuroimaging biomarkers of cerebral small vessel disease (cSVD), and β‐amyloid (Aβ) deposition in cognitive decline and impairment among a diverse cohort of older adults.MethodParticipants at the Wake Forest MESA site were recruited at Exam 6 (2016‐19) to receive additional detailed cognitive testing, cognitive adjudication, and multimodal neuroimaging. Brain MRI on 3T Siemens Skyra, included T1, SWI, FLAIR and NODDI sequences. Total gray matter and white matter hyperintensities (WMH) volumes were adjusted for intracranial volume. A single neuroradiologist graded vascular lesions, including cerebral microbleeds, large and lacunar infarcts. Cognitive decline was measured by the Cognitive Abilities Screening Instrument (CASI) at Exam 5 (2010‐12) and Exam 6 (2016‐19). A subset of 157 participants completed Aβ‐PET at Exam 6 to quantify Aβ burden and positivity (PiB SUVR ≥1.21). Multivariable linear and logistic regression modeled neuroimaging parameters with change in CASI and cognitive status adjusted for age, gender, education, and APOE genotype, considering potential interactions by race.ResultThe imaging sample included 252 participants (53% African‐American and 47% White; aged 72±7 years; 58% women, Table 1). 27% of participants were adjudicated to have mild cognitive impairment (MCI) and 4% had dementia. Aβ positivity (36%) and cSVD (microbleeds in 37% and lacunes in 32%) were common and did not differ by race. Further, temporal lobe cortical thickness and WMH volumes did not differ by race. Lower total gray matter volume, higher WMH volumes, and lower temporal lobe cortical thickness were consistently associated with greater cognitive decline and impairment across racial groups (Table 2). Significant interactions between race and imaging biomarkers with cognitive decline and impairment observed for: greater NODDI Free Water only in White participants and microbleeds and Aβ only in African‐American participants.ConclusionImaging biomarkers indicative of cSVD and Aβ are common in older adults. These biomarkers were not more prevalent in African‐American than White older adults as previously reported; however, they appear to be more strongly related to cognitive decline and impairment among African‐Americans.