bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Age and Sex with Levels of Tau PET in Screened Participants from Auτonomy, a Phase 2 Anti‐p‐tau Monoclonal Antibody Trial in Early Symptomatic Alzheimer’s Disease
Authors: Kolb Hartmuth C. , Fedgchin Maggie M , Quiceno Mary Ellen , Henley David , Saad Ziad S. 
Published: December 2023

AbstractBackgroundThe ongoing Auτonomy trial (NCT04619420) enrolls participants presenting with mild cognitive impairment (MCI) or mild AD dementia with a CDR Global Score of 0.5 and who are tau PET positive. The Janssen plasma p217+tau assay is used as a pre‐screen for eligibility to proceed to tau PET to reduce participant burden and improve screening efficiency. Using preliminary screening data available to date we report on associations of age and sex with tau PET, a biomarker for neurofibrillary tangle (NFT) burden, and with plasma p217+tau levels.Method18F‐MK6240 Tau PET SUVRs for 355 screened participants (180 female) were quantified in Braak Regions Of Interest (ROI)[1] 1 through 6 using cerebellar gray as reference region. Associations were analyzed using a linear model of regional SUVR as a function of age and sex. Additionally, models of association for plasma p217+tau in log(pg/ml) were considered.ResultAge at baseline was not different (p>0.5) for female (70.84 y) versus male (70.49 y) participants. For Braak 3 ROI, tau PET SUVRs showed significant negative association for age (R2
partial = 16%, p<10−14), and increased levels in females (R2
partial = 2%, p<0.01). The results were qualitatively similar across Braak ROIs 1 through 4. For Braak ROIs 5, and 6, the effect of sex was no longer significant, although the trend remained in a consistent direction. For plasma p217+tau, we found significant negative association for age (R2
partial = 7%, p<10−6) and a trend for higher levels in female participants (R2
partial = 1%, p = 0.05).ConclusionIn early Alzheimer’s disease participants who were screened with tau PET for the ongoing Auτonomy trial, higher SUVR was observed for younger versus older participants and in females versus males. The effect of age is likely due to the cohort’s cognitive uniformity whereby in younger participants, a higher tau burden as measured by PET is required for the same level of impairment as older participants[2]. The increased tau PET NFT levels observed in female participants is consistent with findings by Edwards et al. [3]. Associations of similar directions were also observed for plasma p217+tau.[1] Schöll et al., Neuron 2016. [2] Jack et al., Brain 2018. [3] Edwards L et al., Neurobiology of Aging 2021
Light Exposure as a Nonpharmacological Intervention for Alzheimer’s Disease
Authors: Page Erik 
Published: December 2023

AbstractBackgroundIn recent years, significant advances have been made in our understanding of the non‐visible biological impact of light (Vetter et al, 2021). Many of these advances can be traced to the 2002 discovery of a previously unknown retinal photoreceptor known as the intrinsically photosensitive retinal ganglion cell, or ipRGC, which is now known to be connected directly to our master circadian clock in our superchiasmatic nucleus (SCN). Now a growing body of clinical and applied research has shown how light spectrum, intensity, and timing can be used to promote circadian entrainment, leading to significant improvements in human health outcomes, including for people with Alzheimer’s disease and related dementia (ADRD).MethodMany of these clinical studies have used lighting interventions in elder care facilities to evaluate the impact of lighting as a nonpharmacological intervention to improve mood, anxiety, sleep quality, falls and other health metrics for ADRD populations. These studies typically gather light exposure and health metric information during control periods or with control populations using traditional lighting approaches and compare results to periods or populations under “circadian‐enhanced” lighting conditions, which generally means brighter and bluer lighting during the day and dimmer and redder light in the evening and night hours.ResultThe results from these studies have consistently demonstrated significant improvements in circadian entrainment, sleep quality, mood, anxiety, falls and other health metrics for ADRD populations under circadian‐enhanced lighting conditions.ConclusionThis talk will provide an overview of our current understanding of how light exposure impacts human physiology. We will discuss several completed and ongoing clinical studies conducted with ADRD populations, including several studies on which the speaker has been the Principal Investigator. We will cover what questions remain in this area and what studies can be developed in the future to address them. Finally, we will close with a discussion of tools, products, building designs and daily routines that can be applied today by clinicians and caregivers that are most likely to improve the health and wellbeing of ADRD patients based on what is known today about the impact of light exposure.
Life course financial mobility and later‐life memory function and decline by gender and race/ethnicity: an intersectional analysis of a multi‐ethnic cohort study
Authors: Kobayashi Lindsay C , Peterson Rachel , Avila Justina F , Amofa Priscilla A , Vila‐Castelar Clara , Meza Erika , Shaaban C. Elizabeth , Whitmer Rachel A. , Gilsanz Paola , Mayeda Elizabeth Rose 
Published: December 2023

AbstractBackgroundIntersectionality is a theoretical framework capturing joint aspects of social identity (e.g., Black Women experience racism and sexism), which may allow richer understanding of ADRD disparities. We investigated whether life course financial mobility may be differentially associated with later‐life memory function and rate of change across intersectional identities defined by gender and race/ethnicity.MethodData were from KHANDLE and STAR, harmonized cohorts of integrated healthcare system members in Northern California (n = 2,347). Life course financial mobility was defined using measures of financial capital in childhood and adulthood as “consistently high”, “low childhood, high adulthood”, “high childhood, low adulthood”, and “consistently low”. We clustered individuals into 32 strata representing intersectional identities of gender and race/ethnicity across life course financial mobility trajectories. Verbal episodic memory was assessed over three waves using the Spanish and English Neuropsychological Assessment Scales (SENAS). We used mixed‐effects linear regression models with individuals nested within intersectional identity strata, adjusted for early‐life confounders. Models with and without fixed effects of gender, race/ethnicity, and financial mobility were estimated to evaluate if the random effects of the 32 intersectional identity strata contributed variance to the memory intercepts and slopes beyond these additive fixed effects.ResultParticipant mean baseline age was 73 years; 38% were men, 62% were women; 17% were Asian, 48% were Black, 15% were Latinx, and 21% were White. Consistently high financial capital was positively associated with baseline later‐life memory (0.124 SD units; 95% CI: 0.010, 0.238), as was financial mobility from low childhood to high adulthood (0.099 SD units; 95% CI: ‐0.032, 0.230), albeit non‐significantly. Neither was associated with memory decline. In a model without fixed effects of gender, race/ethnicity, and financial mobility, intersectional identities defined by these three factors contributed to 12% of variance in later‐life memory. After adding fixed effects to the model, the impact of intersectional identities on memory variance was reduced to 0.2% (Figure 1).ConclusionConsistently high financial capital and upward financial mobility from childhood to adulthood have positive associations with later‐life memory at baseline, but not rate of change. These association are similar across intersectional identities defined by gender and race/ethnicity.
Within‐network changes in strength of the default mode network relate to Alzheimer’s Disease biomarkers in APOE e4 carriers
Authors: Koenig Katherine A , Durgerian Sally , Lowe Mark J , DiFilippo Frank A , Bekris Lynn M. , Leverenz James B , Rao Stephen M. 
Published: December 2023

AbstractBackgroundResting state functional connectivity measured with MRI (rsfMRI) is disrupted in Alzheimer’s Disease (AD), although reports of rsfMRI changes in adults with the apolipoprotein E (APOE) ε4 genotype (e4+) have been inconsistent. Here, we compare default mode network (DMN) connectivity between e4+ and non‐carriers (e4‐) groups and assess the relationship to AD‐related biomarkers.MethodSixty‐five e4+ (mean age 70.2 ± 4.1; 33 males) and 60 e4‐ (mean age 71.9 ± 4.1; 28 males) subjects underwent a whole‐brain anatomical MPRAGE and a rsfMRI scan. To focus on the DMN, ROIs were placed in the bilateral posterior cingulate cortex (PCC). The most highly correlated voxels between the left and right PCC ROIs were used to calculate left and right PCC rsfMRI z‐maps. Group differences were assessed and mean connectivity in each significant region was correlated with Aβ PET centiloid values and cerebrospinal fluid (CSF) Aβ42/ Aβ40 ratio, phosphorylated‐tau (p‐tau 181), and total‐tau (t‐tau).ResultEight regions showed group differences (p < 0.05; Figure 1). In the e4+ group, right PCC connectivity to the bilateral anterior middle temporal gyri (Figure 1: ROIs 1 and 2) was negatively related to both centiloid score (p < 0.03) and to CSF p‐tau (p < 0.008; Figure 2). Left PCC connectivity to the right anterior middle temporal gyrus was negatively related to centiloid score (r = ‐0.26, p < 0.042) and CSF p‐tau (r = ‐0.31, p < 0.024). Biomarker values in the e4‐ group were not significantly related to connectivity.ConclusionOur findings are consistent with reports of weakened DMN connectivity in e4+ adults and suggest that differences in connectivity strength may be mediated by amyloid or tau deposition.This work was supported by the National Institutes of Health (R01AG022304).
Alzheimer’s Disease (AD): Vitamin B12 deficiency is associated with lower Mini‐Mental State Exam (MMSE) scores
Authors: Komatsu Caroline , Komatsu Ricardo S. 
Published: December 2023

AbstractBackgroundAlzheimer’s Disease (AD) is the leading cause of dementia in the elderly and several lines of evidence indicate that B12 hypovitaminosis is linked to AD. The biochemical pathways involved in AD that are affected by vitamin B12 are APP processing, Aβ fibrillization, Aβ‐induced oxidative damage as well as tau hyperphosphorylation and tau aggregation.Method103 outpatients with the diagnosis of AD conforming to criteria proposed by NINCDS‐ADRDA (2011), followed‐up at a public university hospital, had their vitamin B12 levels assessed and MMSE scores evaluated.Result91 patients (88,35%) presented vitamin B12 normal range (200 – 800 pg/mL) and 12 patients (11,65%) presented vitamin B12 deficiency (≤ 200 pg/mL). From the normal range group, 13 patients (14,29%) presented severe cognitive impairment (MMSE < 10), 33 patients (36,26%) presented moderate cognitive impairment (MMSE = 10 – 20) and 45 patients (49,45%) presented mild cognitive impairment (MMSE > 20). From the deficiency group, 2 patients (16,8%) presented severe cognitive impairment, 5 patients (41,6%) presented moderate cognitive impairment and 5 patients (41,6%) presented mild cognitive impairment. Both groups, vitamin B12 normal range and deficiency, had on average the same educational level: 2,91 and 3,42 years, respectively.ConclusionIn this sample of patients with AD, B12 hypovitaminosis is associated with lower MMSE scores when compared to vitamin B12 normal range.
Psychological pathways linking social networks to verbal fluency decline: Implications for Black‐White cognitive disparities
Authors: Lee Ji Hyun , Sol Ketlyne , Zaheed Afsara B , Morris Emily P. , Palms Jordan D , Scambray Kiana Alexis , Taylor Lauren , Zahodne Laura B. 
Published: December 2023

AbstractBackgroundGrowing literature has identified social networks (SN) as a naturally occurring, modifiable resource for cognitive health. Less is understood about psychological mechanisms through which SN factors influence cognition and whether SN factors play a role in racial cognitive disparities in the US. This study 1) investigated prospective associations between SN factors and changes in verbal fluency; and 2) examined the mediating roles of loneliness and depressive symptoms in the SN‐verbal fluency link among diverse older adults.MethodParticipants were 455 non‐Hispanic Black (NHB) and White (NHW) older adults (Mage = 63.6; 53% Black) from the Michigan Cognitive Aging Project (MCAP), a community‐based, racially balanced, longitudinal study of Black and White adults transitioning to late life in Southeast Michigan. At baseline, participants completed neuropsychological assessments in person and were followed up via telephone two years later. Marital status, living arrangement, network size, network composition, and relationship quality (support and strain) were queried at baseline. We used latent difference score modeling to analyze how SN factors are associated with changes in verbal fluency. Next, a sequential mediation model was used to test for mediating pathways via loneliness and depression.ResultBeing married, larger network size, higher support, and lower strain were each uniquely linked to shallower declines in verbal fluency via lower loneliness and depressive symptoms. Independent of these psychological mediators, having a higher proportion of friends in one’s network was directly linked to shallower declines in verbal fluency. Compared to White participants, Black participants reported a lower proportion of friends and were more likely to have never been married, but they also reported less loneliness.ConclusionOur findings suggest that loneliness and depression represent a psychological stress pathway linking some, but not all, SN features to cognitive decline. Further, Black‐White differences provide evidence of both risk and resilience. Racial disparities in verbal fluency decline were partially explained by a lower proportion of friends (risk) but were partially offset by lower loneliness (resilience) among Black adults. This study highlights the multi‐faceted nature of SN and differential pathways by which SN factors shape cognitive health across racial groups.
Association of Type‐2 diabetes mellitus with voxelwise tau uptake patterns
Authors: Tennant Victoria R , Wheeler Koral V , Lee Noelle , Hall Brandon J , Ances Beau , Toga Arthur W. , Christian Bradley T. , O'Bryant Sid E. , Mapstone Mark , Yaffe Kristine , Braskie Meredith N 
Published: December 2023

AbstractBackgroundDysfunctional insulin signaling and elevated hemoglobin‐A1c (HbA1c) ‐ both associated with type‐2 diabetes mellitus (T2DM) ‐ may result in increased tau hyperphosphorylation, thereby increasing the risk of Alzheimer’s Disease (AD)‐related neuropathology in T2DM patients. Individuals with both AD and T2DM show different profiles of tauopathy compared to individuals with just AD. Here, we evaluated voxelwise tau‐PET patterns with and without T2DM to clarify T2DM‐associated patterns of tau deposition in cognitively intact older adults.MethodWe examined 502 cognitively intact adults from the Health and Aging Brain Study: Health Disparities who had available 18F‐PI‐2620 tau‐PET, florbetaben‐PET (Aβ) (n = 462), MRI T1‐weighted scans (Siemens‐3T), and blood HbA1c levels (n = 492) (Table1). Voxelwise regression models were run in SPM12 using warped 18F‐PI‐2620 standardized uptake value ratio (SUVR) images as the outcome variable (gray matter of the posterior cerebellum reference region) and covarying for age, sex, and education. The first model assessed the effect of T2DM consensus diagnosis on tau uptake. The second model examined the relationship between HbA1c and tau uptake. Both voxelwise regression models were rerun adding global Aβ‐SUVR, obesity, and hypertension as covariates (Figure1).ResultVoxelwise regressions were corrected at voxel p<0.001, cluster FWE p<0.05. T2DM diagnosis was associated with higher 18F‐PI‐2620 uptake in the medial and inferior occipital regions, posterior cingulate, and parahippocampus. Higher HbA1c levels were associated with more 18F‐PI‐2620 uptake in parietal and frontal regions. When covarying for global Aβ‐SUVR, obesity, and hypertension, T2DM diagnosis was associated with 18F‐PI‐2620 uptake in the posterior cingulate. In the HbA1c model, no clusters survived FWE correction after covarying for global Aβ‐SUVR, obesity, and hypertension (Figure1).
ConclusionIndependent of common T2DM comorbidities and brain amyloid, T2DM subjects demonstrated a 18F‐PI‐2620 tau uptake pattern that was different from the characteristic age‐associated medial temporal lobe pattern. Our voxelwise approach allowed us to identify regions that may distinguish T2DM‐related pathology from AD‐related changes. The difference in significant clusters between models could be due to HbA1c levels being controlled by medication in some T2DM patients – an area for future study.
Gyrification abnormalities in young adult presymptomatic carriers of frontotemporal lobar degeneration mutations
Authors: Vargas Andrea Gorham , Lombardi Jolina , Zhang Liwen , Flagan Taru M. , Mandelli Maria Luisa , Brown Jesse A. , Rosen Howard J. , Kantarci Kejal , Ramos Eliana Marisa , Miller Bruce L. , Seeley William W. , Tempini Maria Luisa Gorno , Lee Suzee E. 
Published: December 2023

AbstractBackgroundPresymptomatic C9orf72 expansion carriers show regions of low local gyrification index (lGI) as early as their thirties (Caverzasi et al. JNNP 2019) and regions of gyrification decline have been reported (van Veenhuijzen et al. Ann Neurol 2022). These findings raise the question as to whether abnormal gyrification represents a neurodevelopmental difference or early neurodegeneration in frontotemporal lobar degeneration (FTLD) mutation carriers. Yet, previous studies focusing on young adults is lacking and no study has explored gyrification in the two other common FTLD mutations, GRN and MAPT. Here, we analyzed lGI in young adult presymptomatic FTLD mutation carriers.MethodLGI quantifies buried cortex within the sulcal folds compared to the visible cortex on the outer surface, with larger values indicating more folding (Schaer et al. IEEE trans med imaging 2008). Mean lGI values, as measured by a parcel‐wise analysis implemented in FreeSurfer v.6.0, were compared between 31 presymptomatic (preSx) carriers (12 C9orf72, 13 MAPT, 6 GRN, mean age: 25.2 ± 3.91 years) and 28 demographically‐matched healthy controls (HC: mean age: 25.6 ± 3.8 years). We used ANCOVA to compare all presymptomatic carriers combined (preSxAll) and HC to identify regions with significant lGI differences regressing age, sex, education, handedness, total intracranial volume and scanner type as nuisance covariates. Significant group differences were analyzed by Dunnett’s post‐hoc tests between each mutation subgroup and HC (p<0.05).ResultCompared to HC, preSxAll had higher mean gyrification in the right caudal (F = 5.07, p = 0.03) and rostral anterior cingulate (F = 6.22, p = 0.17), and lower lGI in the left middle temporal gyrus (F = 4.22, p = 0.046). Within these regions, post‐hoc analyses showed that preSx GRN had greater gyrification in the right caudal anterior cingulate (t = 2.57, p = 0.039, 95% CI = [0.005, 0.248]) and preSx C9orf72 had lower lGI in the left middle temporal gyrus (t = ‐3.14, p = 0.009, 95% CI = [‐0.37, ‐0.04]) vs. HC.ConclusionYoung adult FTLD mutation carriers displayed higher gyrification in the right anterior cingulate and lower gyrification in the left middle temporal gyrus compared to HC. Future studies in children will confirm the extent to which these gyrification abnormalities represent neurodevelopmental differences.
Glutathione level variations in brain and blood in healthy aging and Alzheimer’s disease continuum: A systematic review
Authors: Detcheverry Flavie , Mianoor Zainab , Senthil Sneha , Narayanan Sridar , Badhwar AmanPreet 
Published: December 2023

AbstractBackgroundOxidative stress (OS) plays an important role in healthy and pathological aging, particularly Alzheimer’s disease (AD). To protect against the harmful effects of OS, the body uses antioxidants, the most prevalent being glutathione (reduced form, GSH) (Dwivedi et al., 2020). The consistency of GSH perturbations with age and in the AD continuum has not been systematically assessed. We address this knowledge gap by conducting a systematic review of GSH variations in brain and blood in healthy aging and the AD continuum.MethodPubMed searches were conducted up to January 2023. 15 keyword combinations were used to identify studies investigating GSH levels in (i) brain (in‐vivo using magnetic resonance spectroscopy (MRS) and in autopsy tissue using biochemical assays) and/or (ii) blood (plasma, serum) using biochemical assays (Fig1A,B). We considered individuals between 18‐39 years (yrs) as young‐adults, 40‐59 yrs as middle‐aged, and ≥60 yrs as old‐adults.Result42 studies met inclusion criteria (Fig1A,B; Fig2).

BRAIN
: Good to excellent reproducibility was reported by 12 MRS studies (3T, N = 6; 4T, N = 1; 7T, N = 5). For studies investigating age‐specific changes in cognitively unimpaired adults (CU, N = 6), GSH levels were significantly reduced in the majority (50%; temporal, occipital, limbic) of ROIs investigated in old‐ relative to young‐ or middle‐aged adults. Relative to CU, while brain GSH levels were reported to be lower by the majority (5/7) of AD dementia studies, MCI studies lacked consensus, with decreases (N = 3), increases (N = 2) and no significant change (N = 2) reported.

BLOOD
: Blood GSH levels were lower with increasing age in CU (5/7), and further decreased in patients (5/7).In both brain and blood, the majority (4/7) of AD continuum studies assessing cognition reported poorer cognitive functions with lower GSH levels.ConclusionOur systematic review demonstrates that (a) in‐vivo MRS measurements of GSH are reliable; (b) GSH levels in CU generally decrease with increasing age; and (c) GSH levels are reduced in AD relative to age‐matched CU, and reduced GSH is associated with cognitive impairment. Interventions to increase GSH levels may therefore have beneficial effects in AD.