bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Infiltrating Adaptive Immune Cell Signatures from Single‐Nucleus Profiling to Identify Neuroimmune Interactions in Parkinson’s Disease
Authors: Chatila Zena K 
Published: December 2023

AbstractBackgroundAffected brain areas in Parkinson’s disease (PD) show infiltration of T cells, together with increased expression of pro‐inflammatory cytokines and microglia with activated morphology, suggesting that neuroinflammation is plays a complex role in this disorder. To begin elucidating the mechanisms by which infiltrating adaptive immune cells may contribute to the demise of neurons in PD, we sought to investigate changes in T cell transcriptional signatures at the single‐cell level in post‐mortem human tissue. We also investigated the transcriptional signatures of microglia to capture interactions between the innate and adaptive immune system.MethodWe applied a single nucleus RNA‐sequencing approach to generate an unbiased transcriptomic dataset in 19 sporadic PD cases across the substantia nigra (SN), ventral tegmental area, substantia innominata, and hypothalamus, and in the SN of 14 controls.ResultWe identified three subpopulations of CD8+ T cells which are enriched in the PD SN, and a natural killer (NK) cell population is enriched in the SN of controls. These findings parallel those of other studies that show CD8+ T cells are enriched in the PD brain, and those that suggest NK cells may play a protective role against disease. In parallel, we identified a microglial subpopulation that is present in the SN of controls but depleted in SN tissue from donors with PD; this microglial population has higher expression of antigen‐presentation proteins, suggesting unique interactions with the adaptive immune system. Immune cell‐cell interactions between the identified T cell, NK cell, and microglial subpopulations were investigated through assessing co‐regulation of ligand‐receptor pairs. Unique interactions were found in the PD SN which are suggestive of recruitment of activated microglial populations to the SN by T cells, as well as T cell and microglial inhibition of NK cell signaling.ConclusionThese findings suggest an imbalance between CD8+ T cell and NK cell activity in the PD SN, and a role for T cells in microglial activation in PD. We aim to integrate our immune genomic data with neuronal data to generate a signature of neuroimmune interactions in PD, which may ultimately be used to develop biomarkers and candidate molecules/pathways to therapeutically target specific immune interactions.
Microglial TREM2 senses TDP‐43 and protects against TDP‐43‐related neurodegeneration
Authors: Wu Long‐Jun 
Published: December 2023

AbstractBackgroundTriggering receptor expressed on myeloid cell 2 (TREM2) is a surface receptor that, in the central nervous system, is exclusively expressed on microglia. TREM2 variants have been linked to increased risk for neurodegenerative diseases, but the functional effects of microglial TREM2 in TAR‐DNA binding protein 43 kDa (TDP‐43)‐related neurodegeneration remain largely unknown.MethodWe investigated TDP‐43 neurodegeneration via viral‐mediated expression of hTDP‐43 protein in mice or inducible expression of hTDP43 with defective nuclear localization signals in transgenic mice. Mass cytometry analysis, mass spectrometry, surface plasmon resonance, and computational simulation were used to study the interaction between TREM2 and TDP‐43.ResultWe found that TREM2 deficiency impaired microglia phagocytic clearance of pathological TDP‐43, and enhanced neuronal damage and motor function impairments. hTDP‐43 induced a TREM2‐dependent subpopulation of microglia with high CD11c expression and higher phagocytic ability. We further demonstrated an interaction between TDP‐43 and TREM2, in vitro and in vivo, in hTDP‐43‐expressing transgenic mouse brains. We computationally identified the region within hTDP‐43 that interacts with TREM2 and observed the potential interaction in ALS patient tissues.ConclusionOur data reveal the novel interaction between TREM2 and TDP‐43, highlighting that TDP‐43 is a potential ligand for microglial TREM2 and the interaction mediates neuroprotection of microglial TREM2 in TDP‐43‐related neurodegeneration.
Accordance to a MIND–Style Diet is Associated with Decreased Risk of Dementia Mortality in the REasons for Geographic and Racial Disparities in Stroke (REGARDS) Cohort
Authors: Judd Suzanne E , Howard George , Tangney Christy C , Pearson Keith , Shikany James M , Cushman Mary , Wilson Nicole , Howard Virginia J , Sawyer Russell , Oladele Carol , Manly Jennifer J. 
Published: December 2023

AbstractBackgroundThe Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet (high in nuts, seeds, vegetables, berries and low in meat, dairy, and butter) has been associated with reduced risk of dementia. However, no studies have examined the role of the MIND diet in a racially diverse population nor have there been studies that have examined the association of the MIND diet with dementia mortality.MethodWe examined data from Black and White adults (age 45‐98) in the US‐based REGARDS cohort. Dietary and covariate data were collected at baseline (2002‐2007). MIND diet score was created as described by other cohort studies (Table footnote). The primary outcome was dementia‐related mortality through December 31, 2020 from the National Death Index using ICD‐10 codes F00‐F03, G30, G31.0‐G31.1, and R54. Cox proportional hazards regression was used to model MIND diet score (in tertiles and as a continuous variable) and time to dementia death. To ensure robust association across sub‐groups, we tested for interactions of MIND diet with sex, race, age, obesity, history of stroke, and baseline cognitive impairment and adjusted for competing risks.ResultA total of 18,277 participants (mean age 64.9) had dietary data available to calculate the MIND diet score. MIND diet score was higher among females compared with males, White compared with Black participants, and college graduates. There were no differences in accordance by age. After a median of 12 years, participants with the highest MIND diet scores had the lowest risk of dementia death HR = 0.78 {95% CI; (0.66, 0.94)} comparing the 3rd tertile with the 1st tertile and after adjustment for age, race, sex, income, education, total energy, and other medical conditions (Table). This association was attenuated slightly when a competing risk analysis was considered HR = 0.84 {95%CI; (0.70, 1.00)}. There were no significant interactions observed.ConclusionThe MIND diet score is associated with dementia death in a large bi‐racial cohort in the US. This association is robust across race, age, and sex groups. Dietary interventions using the MIND diet may further clarify whether this association is causal and whether MIND diet may be an important tool in reducing rates of dementia.
Longitudinal effects of sex on pathology accumulation, neurodegeneration and cognitive decline in Presenilin‐1 E280A mutation carriers: preliminary findings from the Colombia‐Boston (COLBOS) biomarker study
Authors: Vila‐Castelar Clara , Baena Ana Y. , Langella Stephanie , Munera Diana , Aguillon David , Alvarez Sergio , Sanchez Justin S , Kaplan Elizabeth , Aduen Paula , Guzman‐Velez Edmarie , McDowell Celina F. Pluim , Martinez Jairo E. , Noriega Daisy , Badillo‐Cabrera Alex L , Félix Nikole A Bonillas , Fabrega‐Ching Sofia , Ramirez‐Gomez Liliana A. , Giudicessi Averi , Lee Hang , Johnson Keith A. , Sperling Reisa A. , Lopera Francisco , Quiroz Yakeel T. 
Published: December 2023

AbstractBackgroundPrevious work showed that females at risk for autosomal dominant Alzheimer’s disease (AD) due to a single mutation (E280A) in the Presenilin‐1 gene (PSEN1) may have greater cognitive resilience to AD‐pathology and neurodegeneration than males. However, more research is needed to clarify the effect of sex on AD risk and progression. We investigated the effects of sex on rates of amyloid and tau accumulation, neurodegeneration, and memory decline in PSEN1 mutation carriers with and without cognitive impairment, who are genetically determined to develop early‐onset dementia.MethodA total of 66 cognitively unimpaired mutation carriers (mean age of 34.41 +/‐ 4.86 years; 38 females), and 23 cognitively impaired mutation carriers (mean age of 44.91 +/‐ 2.83 years; 17 females) from the Colombia‐Boston Biomarker (COLBOS) study completed baseline cognitive assessments. A subset of 52 participants also completed florbetapir‐ and flortaucipir‐PET, and structural MRI. Cognitive and neuroimaging follow‐up visits were completed at 2‐ (n = 29) and 4‐year (n = 13) intervals. We used linear mixed‐effects models, with random intercepts, to predict rate of change in MMSE scores, CERAD word list delayed recall, cortical amyloid burden, tau in the entorhinal, inferior temporal, and precuneus cortices, and hippocampal volume by sex, controlling for education.ResultOver time, carriers exhibited greater cortical amyloid burden (p<.001), inferior temporal tau (p = .019), precuneus tau (p = .003), lower hippocampal volume (p = .005), and showed a trend towards lower MMSE scores (p = .059) and word list delayed recall (p<.080); entorhinal tau did not significantly increase (p = .137). Female carriers showed a steeper decline in word list delayed recall than male carriers (p = .021). There were no sex differences in the rate of accumulation of mean cortical amyloid or regional tau, hippocampal atrophy, or change in MMSE scores (all ps>.05).ConclusionPreliminary findings of this ongoing study suggest that despite similar rates of pathology accumulation or atrophy between female and male PSEN1 E280A carriers, female mutation carriers may have faster memory decline. Future analyses with additional participants and follow‐up intervals are needed to characterize sex differences in ADAD risk and resilience, as well as inform development of treatments and interventions.
A Dyadic Behavioral Sleep Intervention Program for Persons Living With Dementia and Their Family Caregivers: A Pilot Randomized Controlled Trial
Authors: Song Yeonsu , Papazyan Anna , Lee Diane , McCurry Susan M , Mitchell Michael N. , Irwin Michael R , Teng Edmond , Alessi Cathy A , Martin Jennifer L 
Published: December 2023

AbstractBackgroundUntreated sleep problems in persons living with dementia (PLWD) and their caregivers impact health outcomes of both individuals and impair quality of care for caregivers. This study pilot tested preliminary effects of a dyadic sleep intervention program among this group.MethodThirty PLWD/caregiver dyads were randomized to a 5‐session treatment (n = 15 dyads) or a similarly structured information‐only control group (n = 15 dyads) via in‐person or video‐telehealth. Treatment was a manual‐based program incorporating key components of cognitive behavioral therapy for insomnia (CBTI), daily light exposure and walking, and a problem‐solving approach for dementia‐related behaviors and caregiving challenges. Sleep outcomes included actigraphy‐measured sleep efficiency (SE) and total awake time (TWT) at night for dyads, and Pittsburgh Sleep Quality Index (PSQI) for caregivers. Outcomes were measured at baseline, post‐treatment, and 3‐months follow‐up (main outcome time point). Recommendation adherence in the treatment group was computed and a 2 (group) by 3 (time) mixed model analysis of variance was used to test the treatment effects (p<0.20 as the threshold).ResultTwo dyads in treatment and one control dyad did not complete all five sessions. Of 13 dyads who completed all sessions of the treatment program, average % days that the dyads met their sleep schedules were 76% bedtime and 83% get‐up time for PLWD and 81% bedtime and 68% get‐up time for caregivers. From baseline to 3‐month follow‐up, SE increased by 3.2% more for PLWD in the treatment group (n = 9) compared to control (n = 9, p = 0.48) and by 3.7% more for caregivers in the treatment group (n = 12) compared to control (n = 9, p = 0.17). TWT also reduced by 19 minutes more for PLWD and 14 minutes more for caregivers in the treatment group compared to control at the 3‐month follow‐up although this was not statistically significant. Caregivers in treatment also showed non‐significant improvement on the PSQI (p>0.20).ConclusionA dyadic approach to sleep improvement showed evidence of benefit among PLWD and caregivers. A larger study is needed to fully evaluate these effects and compare in‐person to telehealth modalities.
Combining virtual mentalizing imagery therapy with caregiving skills for Spanish language Latino family dementia caregivers: a feasibility and acceptability study
Authors: Gomez Liliana Ramirez , Gutierrez‐Ramirez Paulina , Melero‐Dominguez Maria , Madarasmi Saira , Quiroz Yakeel T. , Jain Felipe A 
Published: December 2023

AbstractBackgroundSpanish‐speaking family caregivers of people living with dementia have limited supportive resources in Spanish. There are few validated, culturally acceptable virtual interventions to reduce these caregivers’ psychological distress and address caregiving skill needs. We investigated the feasibility of virtual delivery of a Spanish language adaptation of mentalizing imagery therapy (MIT), which provides guided imagery and mindfulness training to improve self‐ and other‐ understanding and reduce negative psychological symptoms, in combination with caregiver skills (CS).Methods16 Spanish‐speaking Latino family dementia caregivers enrolled in a combined 8‐week virtual MIT‐CS program. Feasibility, acceptability, and satisfaction with MIT‐CS were assessed. The primary psychological outcome was depressive symptoms; secondary outcomes included caregiver burden and dispositional mindfulness. Feasibility thresholds for participation were set at 75% for retention, at 75% for group attendance, and at two times per week for MIT home practice. Acceptability was evaluated as overall satisfaction with MIT‐CS of at least four points on a five‐point Likert scale. Effect sizes were estimated with Cohen’s d, and statistical significance was computed with mixed linear models.ResultsCaregivers were 58±8 (mean±SD) years of age, 81.2% female, and had an average of 14±3 years of education. 69% did not have a 4‐year college degree. 94% of participants completed the group (one participant dropped out due to time constraints). Participation in weekly group meetings was 86%. Home MIT practice was performed on average 2.2±0.3 times per week. Satisfaction with MIT‐CS reached 4.5±0.9 of a possible 5 points (most responses rated excellent). Reduction in depression was observed after completion of MIT‐CS (d = ‐.42, p = .03). There was a significant improvement in mindfulness (d = .91, p = .004) and a trend toward improvement in caregiver burden (d = ‐.44, p = .1).ConclusionsVirtual group‐delivered MIT‐CS was feasible and acceptable in a group of Latino Spanish language family dementia caregivers living in the greater Boston area. MIT‐CS demonstrated promising effect sizes for reducing depressive symptoms and caregiver burden and increasing mindfulness. Larger, randomized controlled trials of MIT‐CS should validate the efficacy of specific MIT‐CS components in this population.
Sex‐specific neuropsychiatric burden distinguished by APOE4 status and cortical thickness
Authors: Khoury Marc A , Valcic Mila , Churchill Nathan W , Fornazzari Luis R , Mortby Moyra E , Ismail Zahinoor , De Luca Vincenzo , Munoz David G. , Schweizer Tom A. , Fischer Corinne E. 
Published: December 2023

AbstractBackgroundThe APOE ε4 (APOE4) allele is a genetic risk factor for Alzheimer’s disease (AD). Prior work by our group found a significant association between the APOE4 allele and presence of psychosis as well as overall increased neuropsychiatric symptom (NPS) burden in female APOE4 homozygote AD patients, with no effect present in males. In this study, we sought to examine the relationship between APOE4 carrier status and sex on NPS burden from a neuroimaging perspective, with the aim to determine what brain regions may be driving this effect.MethodA cohort of 752 AD patients were selected from the National Alzheimer’s Coordinating Center (NACC) database: 104 APOE4 homozygotes (40F|64M), 304 APOE4 heterozygotes (160F|144M) and 310 APOE4 non‐carriers (131F|179M). Presence of NPS was identified using the Neuropsychiatric Inventory (NPI). Structural T1‐weighted images were downloaded from the NACC imaging dataset and cortical thickness measures corresponding to frontal, cingulate, temporal and parietal regions were assessed. Statistical analysis included a Bayesian multilevel regression where cortical thickness was modeled as an outcome variable against an interaction between sex and APOE4 homozygote status (0|1), while controlling for heterozygote status, APOE4 non‐carrier status, age, sex and MMSE as predictor variables. Within‐ and between‐groups mean differences in thickness were measured as a probability density estimate (Highest Density interval), and partial correlation was used to examine NPI correlates to thickness.ResultFemale APOE4 homozygotes displayed a high probability (>90%HDI) of greater cortical thickness in the posterior cingulate and isthmus cingulate regions bilaterally and reduced cortical thickness in temporal regions (Figure 1). Cortical thickness in the fusiform cortex was positively correlated to greater NPI burden (p<0.05) among female homozygotes, and negatively correlated to NPI burden among female heterozygotes. Cortical thickness in males, regardless of carrier status, did not correlate to NPI burden in any region.ConclusionThis study highlights an important relationship between the fusiform cortex and NPI burden in female APOE4 carriers, marking a female‐specific effect. Future work should further disentangle sex differences in APOE4 status and psychosis with a focus on the fusiform cortex as a potential region of interest.
The diagnostic and prognostic potential of plasma GFAP in older adults with subjective memory complaints at risk of Alzheimer’s disease
Authors: Chatterjee Pratishtha , Pedrini Steve , Doecke James D , Dore Vincent , Goozee Kathryn G , Taddei Kevin , Sohrabi Hamid R , Maruff Paul , Villemagne Victor L , Rowe Christopher C , Masters Colin L , Martins Ralph N 
Published: December 2023

AbstractBackgroundThe astrocyte cytoskeletal protein, Glial Fibrillary Acidic Protein (GFAP), is a potential blood‐based biomarker for diagnosis and prognosis of older adults in the Alzheimer’s Disease (AD) continuum, comprising cognitively unimpaired (CU) and cognitively impaired individuals with high brain amyloid‐beta load (Aβ+). However, specific attention to the potential of plasma GFAP in CU Aβ+ older adults with Subjective Memory Complaints (SMCs) is required, given that SMCs are a primary feature of Subjective Cognitive Decline (SCD) and individuals with SMCs are twice as likely to develop dementia compared to non‐memory complainers.MethodPlasma GFAP was measured in older adults with SMCs from two independent cohorts, namely the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH; N = 76; 52 Aβ‐, 24 Aβ+) and the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL; N = 75; 50 Aβ‐, 25 Aβ+), using the Neurology‐4PlexA and Neurology‐4PlexE kits, respectively, on the Single Molecule Array (Simoa) platform (Quanterix). The Memory Assessment Clinic‐Q was used to assess participants with SMCs.ResultPlasma GFAP was significantly elevated in Aβ+ SMCs compared with Aβ‐ SMCs in both cohorts before and after adjusting for age, sex and APOE ε4 carrier‐status (mean±SD in pg/mL; KARVIAH: Aβ‐ = 148±47, Aβ+ = 230±93, p<.0001; AIBL: Aβ‐ = 135±58, Aβ+ = 209±76, p<.0001). Plasma GFAP differentiated Aβ+ SMCs from Aβ‐ SMCs with an area under the receiver operating characteristic curve (AUC) of 80% (CI:68%‐92%) in KARVIAH and 77% (CI:66%‐89%) in AIBL. Based on the AUC, plasma GFAP performed equivalent to other putative plasma AD diagnostic markers such as plasma phosphorylated‐tau181 (p‐tau181) and plasma Aβ42/Aβ40 ratio but performed significantly better than plasma Neurofilament Light (NfL) in both cohorts (p<.05). A model comprising plasma GFAP, p‐tau181, Aβ42/Aβ40 ratio and the AD risk factors, age, sex and APOE ε4 carrier‐status significantly outperformed any of the biomarkers alone in differentiating brain Aβ‐/+ status in both cohorts (p<.05). Higher plasma GFAP in individuals with SMCs was associated with faster cognitive decline assessed by the Preclinical Alzheimer Cognitive Composite (PACC) score and with faster brain Aβ accumulation assessed by PET in AIBL.ConclusionThese observations suggest that plasma GFAP has diagnostic and prognostic value for older adults at risk for AD.
Application of the mild behavioral impairment checklist in Chinese patients with the behavioral variant of frontotemporal dementia
Authors: Cui Yue , Liu Li , Chu Min , Xie Kexin , Chen Zhongyun , Wu Liyong 
Published: December 2023

AbstractBackgroundThe mild behavioral impairment checklist (MBI‐C) designed to capture neuropsychiatric symptoms in the whole spectrum of elder with or without dementia, have been verified in mild behavioral impairment, mild cognitive impairment and Alzheimer’s Disease, but never used in the behavioral variant of frontotemporal dementia (bvFTD).MethodFifty‐two patients with bvFTD (mild, n = 30; moderate‐severe, n = 22) and 82 community‐dwelling elderly individuals (HCs) were enrolled. All subjects were assessed with a full neuropsychological scale including the MBI‐C, Neuropsychiatric Inventory Questionnaire (NPI‐Q), and Frontal Behavioral Inventory (FBI). Receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the MBI‐C, NPI‐Q, and FBI, and cutoff points were determined using the Youden index.ResultThe MBI‐C and domain scores in all patients with bvFTD were significantly higher than those in HCs. The most common symptoms of bvFTD were apathy (82.7%) and impulse dyscontrol (80.8%). The MBI‐C score was positively correlated with the NPI‐Q, FBI, and Activities of Daily Living. For differentiating patients with both bvFTD and mild bvFTD from HCs, the optimal MBI‐C cutoff point was 5/6 with a sensitivity of 100% and specificity of 82%, and its sensitivity was higher than that of the NPI‐Q and FBI.ConclusionThe MBI‐C is a sensitive tool for screening behavioral and psychological symptoms in patients with bvFTD, even in the early stages of the disease.