bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood‐based glial reactivity modulates cerebral amyloid and tau deposition in Alzheimer's disease
Authors: Lan Guoyu , Li Anqi , Yang Jie , Zhang Laihong , Fang Lili , Zhu Yalin , He Zhengbo , Zhou Xin , Liu Lin , Sun Pan , Cai Yue , Guo Tengfei 
Published: January 2025

AbstractBackgroundPlasma biomarkers of Alzheimer’s disease (AD)‐related pathological changes are considered as proxies of their changes in the brain. Recent cohort studies reported very early changes in plasma astrocytic marker glial fibrillary acidic protein (GFAP) in the AD spectrum, which is relative to the onset of neuropathology. Little is known about the association between plasma soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and primary AD pathology. This study explored how GFAP and sTREM2 in plasma influence cortical β‐amyloid (Aβ) and tau deposition.MethodWe measured the concentrations of plasma biomarkers by the Simoa or MSD platforms in a total of 285 individuals from the Greater‐Bay‐Area Healthy Aging Brain Study (GHABS) cohort, a large community‐based cohort study of older adults from China. All of them underwent Aβ PET imaging ([18F]‐D3FSP or [18F]‐florbetapir), and 104 individuals were additionally scanned for tau PET imaging. We investigated the modification effect of plasma glial biomarkers (GFAP and sTREM2) on Aβ PET and tau PET using generalized linear models, controlling for age, sex, and diagnosis.ResultPlasma GFAP but not sTREM2 interacted with Aβ42/Aβ40 and p‐Tau181 (Table 1), where higher GFAP levels were associated with steeper relations of lower Aβ42/Aβ40 and higher p‐Tau181 with elevated Aβ PET. Regarding tau PET, we found that higher plasma GFAP levels enhanced the association between plasma p‐Tau181 and tau PET. In contrast, higher plasma sTREM2 levels attenuated the associations of lower Aβ42/Aβ40 and higher p‐Tau181 with tau PET elevations. Congruent results were obtained when we used Aβ PET as the interaction term in the models. Furthermore, higher plasma sTREM2 levels also mitigated the association between plasma GFAP and tau PET but did not influence Aβ PET (Figure 1). At the voxel level, the association between plasma GFAP and tau PET was diminished and limited in individuals with above‐median sTREM2 levels versus individuals with below‐median sTREM2 levels.ConclusionThis study provides novel insights into the link between plasma glial biomarkers and cortical deposition of Aβ and tau aggregates, where plasma GFAP is linked to augmented Aβ and tau pathology, whereas plasma sTREM2 is linked to attenuated tau accumulation.
Setting a Baseline for Normal Cognitive Aging with Lexical Concreteness – A Corpus Linguistic Approach
Authors: Han Kunmei 
Published: January 2025

AbstractBackgroundIdentifying language variation in healthy aging speakers is important for understanding normal cognitive aging. Setting a baseline of normal aging languages in the first place is necessary for the evaluation of language performances of old adults. Lexical concreteness, a well‐studied psycholinguistic parameter, has been used to detect semantic memory‐related deficits. For example, people with semantic dementia were found to display reduced lexical concreteness (Breedin et al., 1994). Healthy old adults, however, are less studied in terms of the concreteness pattern in their speech. This study examines lexical concreteness of free speech samples of normal aging speakers age between 60 – 80 in Singapore.MethodWe collected about 15‐min free speech from 243 English‐speaking, cognitively healthy Singaporeans (133 women, 110 men) age above 60 years old. Demographic variables (age, gender, education, and number of languages spoken) were uncorrelated with each other. Speeches were transcribed by native Singapore English speakers and tagged with part‐of‐speech (PoS) information. We calculated global lexical features including speech rate (in minutes), lexical diversity (Moving‐Average Type‐Token Ratio), and PoS distribution (count per 100 tokens). Then we calculated concreteness (Brysbaert et al., 2014) of major content words for every individual. The relation between age and lexical measures was examined with Spearman’s correlation test.ResultResults of the statistical analysis show that healthy old adults speak slower (𝜌= ‐0.14, p= .03) with more concrete nouns (𝜌= 0.14, p= .03) and adjectives (𝜌= 0.18, p< .05) than younger speakers. PoS distribution and verb concreteness (all p> .05) remain stable in the aging process.ConclusionOur speech sample revealed a general trend of elderly speech – reduced speech rates and increased lexical concreteness. The significant positive association between age and lexical concreteness in free speeches of health old adults was found for the first time, providing corroborative evidence for the link between concreteness and semantic memory. We also found a dissociation between nouns and verbs, consistent with neuropsychological literatures that nouns and verbs are encoded in different areas of the brain (Vigliocco et al., 2011). In sum, measuring lexical concreteness in natural speech data can provide circumstantial evidence for evaluating cognitive aging.
Serum brain‐derived neurotrophic factor and progression to MCI in cognitively normal older adults
Authors: Kim Kyungtae , Byun Min Soo , Yi Dahyun , Jung Joon Hyung , Sohn Bo Kyung , Jung Gijung , Ahn Hyejin , Lee Jun‐Young , Lee Yun‐Sang , Kim Yu Kyeong , Lee Dong Young 
Published: January 2025

AbstractBackgroundBrain derived neurotropic factor (BDNF) has been associated with improved neuronal survival and synaptic plasticity and long‐term memory. Some human studies also reported the relationship between lower blood BDNF levels and poorer memory function and dementia. A prior longitudinal study also demonstrated higher serum BDNF levels were associated with lower risk of overall dementia and Alzheimer’s disease (AD) dementia. However, it remains uncertain whether reduced serum BDNF levels precede the onset of mild cognitive impairment (MCI), which is known as pre‐dementia stage. This study aimed to examine whether higher serum BDNF in cognitively normal (CN) older adults is related to less common progression to MCI and to identify potential moderators of this relationship.MethodA total of 278 CN older adults between 55 and 90 years of age were enrolled. All participants underwent comprehensive clinical assessments, serum BDNF level measurement, and multimodal brain imaging including Pittsburgh compound B (PIB)‐positron emission tomography (PET) at baseline, and followed up for up to 4 years. Serum BDNF levels were divided into two categories by median value of serum BDNF level: < 21448.5 pg/mL (low BDNF), and > 21448.5 pg/mL (high BDNF). Cox model was used to analyze the relationship between baseline BDNF levels and the risk for MCI progression controlling for potential confounders. We also ran sensitivity analyses stratified by sex, age, education, apolipoprotein E ε4 (APOE4) positivity, and amyloid PET positivity.ResultDuring follow‐up, 24 participants developed MCI. Controlling for age, sex, education and APOE4 positivity, low BDNF group had significantly more frequent progression to MCI than high BDNF group (hazard ratio for MCI, 2.98; 95% CI, 1.17‐7.56; p=0.02) and these association persisted even after controlling for amyloid PET positivity and vascular risk factor score as additional covariates (hazard ratio, 2.98; 95% CI, 1.17‐7.55; p=0.02). Sensitivity analyses revealed that the associations were apparent only among women, participants aged younger than 75 years, those without college degrees, and amyloid negative participants (Table).ConclusionHigher serum BDNF levels may protect against future occurrence of MCI in cognitively healthy older adults. Such influence appears more prominent in women and younger, less educated, or amyloid PET negative individuals.
Psychometric evaluation of the Chinese modified perceived neighborhood cohesion scale in older adults at high risk of cognitive impairment
Authors: Chiu Yi‐Chen , Lin Mei‐Hsuan , Hsu Pei‐Chen , Hsu Wen‐Chuin , Chen Yi‐Chun 
Published: January 2025

AbstractBackgroundThe global increase in dementia cases underscores the need for community‐based services, particularly for older adults who spend significant time in their neighborhoods. This context profoundly influences cognitive function and quality of life, especially in those at high risk of cognitive impairment. Despite its importance, neighborhood cohesion has not been extensively studied in this group. This study aimed to assess the reliability and validity of the Chinese Modified Perceived Neighborhood Cohesion Scale (CMPNCS) in Northern Taiwanese older adults at high risk of cognitive impairment.MethodA cross‐sectional, mixed‐methods approach was employed. Qualitative interviews with 10 stakeholders, including at‐risk older adults and community leaders in Northern Taiwan, informed the adaptation of the English Perceived Neighborhood Cohesion Scale into a 13‐item Chinese version. Quantitative phase applied the convenient sampling method to recruit 125 older adults with high risk of cognitive impairment in communities in Northern Taiwan. A trained research assistant administered the revised scale face‐to‐face to 125 older adults identified as high‐risk for cognitive impairment. Psychometric properties assessed included expert validity (Content Validity Index), exploratory factor analysis, internal consistency (Cronbach’s Alpha), and 7‐day test‐retest and inter‐rater reliability.ResultsThe quantitative phase results are listed as follows. The participant demographic was 31.2% male and 68.8% female, primarily aged 70‐74 (27.2%) and ≥75 (27.2%). The Content Validity Index was 0.94. Exploratory factor analysis yielded a three‐factor solution: Trust in the Neighborhood (Cronbach’s Alpha = 0.84), Community Leader Action (Cronbach’s Alpha = 0.68), and Cohesion in the Neighborhood (Cronbach’s Alpha = 0.77). Overall internal consistency was high (Cronbach’s Alpha = 0.88), with excellent 7‐day test‐retest (0.92) and inter‐rater reliability (0.99).ConclusionThe CMPNCS exhibits strong psychometric properties, making it a valuable tool in nursing research. It enables the assessment of neighborhood cohesion and the exploration of its relationship with cognitive function in at‐risk older adults. The findings can guide community health nurses in enhancing perceived community cohesion and developing tailored environmental interventions for this population.
Immunohistochemical study of the bcl‐2 in the pyramidal layer of the hippocampus in rats in hypertensive encephalopathy modeling
Authors: Mednikov Dmitry , Smirnov Alexey Vladimirovich , Tyurenkov Ivan Nikolaevich 
Published: January 2025

AbstractBackgroundClosely related to the subfamily of proapoptotic proteins is the antiapoptotic protein bcl‐2, which acts as an intracellular blocker of the mitochondrial apoptotic pathway. By inhibiting the action of effector caspases, as well as blocking the release of AIF and cytochrome C, Bcl‐2 prevents regulated cell death and ensures survival in conditions of damage.MethodThe study was performed on Wistar rats, which were subjected to gravitational overloads (9g) in the caudocranial vector for 5 minutes twice a day for 28 days.ResultAn immunohistochemical study using antibodies to bcl‐2 in a group of rats with simulated hypertensive encephalopathy revealed a heterogeneous positive cytoplasmic reaction, mostly moderately expressed. In individual pyramidal neurons and glial cells, expression was mosaic in nature, where both dusty accumulation of IRM of weak intensity and deposits of more pronounced intensity were detected. Visually more intense staining was detected in neurons with deformed perikarya against the background of pronounced edema. Increased expression of bcl‐2 was also manifested in an increase in the relative area of the IRM. In CA1 of rats of the study group, this the indicator increased by 3.9% compared to the control (p<0.01). The most significant increase in the relative area of bcl‐2‐positive material was detected in CA2 and CA4, increasing, respectively, compared to the control by 5.6% (p<0.01) and 5.7% (p<0.01).ConclusionHigher activity of bcl‐2 in the CA1 and CA3 zones may be one of the factors for the greater stability of CA2 and CA4 in relation to CA1 and CA3.
The Association between Comorbidities and Cognitive Function: Findings from the Health and Retirement Study
Authors: Su Yan‐Jhu , Alberth Andrew , Rataj Alison C , Stam Elisabeth 
Published: January 2025

AbstractBackgroundCognitive function has been linked to factors including physical health and individual characteristics (e.g., race, ethnicity). However, few studies have examined these associations simultaneously. Therefore, this study examined the relationship between chronic conditions and cognitive function, and whether this differed for people across race and ethnicity among adults 65 years old and older in the United States.MethodThis cross‐sectional study uses data from the 2018 Health and Retirement Study (HRS). The sample includes adults, age 65 years and older, who were employed in 2018 (N = 8,310). The main dependent variable is respondents’ cognitive function (TICS‐35) in 2018 and the independent variable is the different chronic illness conditions and chronic illness count. Race and ethnicity are assessed as moderators. Ordinary least squares (OLS) regression models are utilized in this investigation.ResultThe results show that individuals with chronic lung disease such as chronic bronchitis or emphysema (b = ‐.56, p = .001), stroke (b = ‐.56, p<.001), or psychological issues (b = ‐.71, p<.001) had lower cognitive function scores than other individuals. Moreover, racial and ethnic differences were observed, specifically older Black adults with psychological issues scored lower on cognitive function scores when compared to White older adults (b = ‐.73, p = .075). Older adults with more chronic illnesses had a lower cognitive function score (b = ‐.11, p = .01) and racial and ethnic differences were observed as well, specifically older Hispanic adults with more chronic illness had lower cognitive function than White older adults (b = ‐.25, p = .035)ConclusionFindings demonstrate that people with more chronic illnesses may experience lower cognitive functioning, and racial and ethnic minorities may be particularly more vulnerable. Therefore, the prevention of chronic diseases plays an extremely important role in the cognitive health of older adults, specifically for vulnerable populations. Additionally, for racial and ethnic minorities, more emphasis may need to be placed on the prevention of chronic diseases. Policies aimed at preventing disease and promoting healthy lifestyles may also help improve cognitive functioning.
Unravelling Frontotemporal Dementia: Exploring the GABA and Glutamate Hypothesis through Semantic Deficits
Authors: Ilchovska Zlatomira Georgieva , Hosseini Akram A. , Jung JeYoung 
Published: January 2025

AbstractBackgroundSemantic cognition refers to our ability to manipulate and generalize knowledge and plays a critical role in communication and daily activities. Therefore, impairments in semantic cognition can have a severe impact on quality of life (e.g., dementia). Frontotemporal dementia (FTD) is the cause of 12.5‐16.5% of all degenerative dementias. It is a heterogeneous group of clinical syndromes marked by progressive neurodegeneration of the frontal and temporal lobes – key regions for semantic cognition. Recent studies highlight the importance of addressing neurotransmitter deficits in FTD, particularly in glutamate and GABA. Though pathologically distinct, FTD syndromes share common neurotransmitter deficits – ‘GABA and glutamate hypothesis of FTD’. We investigate this hypothesis by linking GABA and glutamate changes with semantic deficits in FTD patients.MethodsWe utilized MR spectroscopy, a non‐invasive, in‐vivo technique, to measure neurochemicals, including GABA and glutamate, in the brain. Our study involved 7 FTD patients, 2 typical Alzheimer’s disease (AD) patients with a symptomatic amyloid status serving as a control patient group (expected to show general cognition deficits but not specifically semantic ones, neither semantic‐specific neurotransmitter changes like those in the FTD), and 23 age‐matched healthy controls (HC). We assessed neurotransmitter concentrations in the temporal and frontal cortex, conducted computerized semantic tasks, and administered cognitive batteries assessing language, memory, attention, and executive function.ResultsFTD patients showed deficits in language, memory, and executive function compared to AD patients and HCs (see Figure 1). AD patients also showed decreased general cognition compared to HC. Importantly, FTD patients performed the semantic task less effectively than ADs and HCs (see Figure 2). The balance between excitation and inhibition (EIB = glutamate/GABA) was significantly decreased in the temporal lobe in FTD patients compared to HCs (see Figure 3).ConclusionsFTD demonstrated cognitive deficits in language, memory, and executive function, along with decreased semantic task performance and reduced EIB in the temporal lobe. These preliminary findings support the GABA and glutamate hypothesis of FTD. Ongoing data collection on this CogNID project (IRAS reference: 250525, clinical trial reference: NCT03861884) will provide additional results, with more patient data to be presented at the AAIC conference.
Life’s Essential 8, cardiovascular health, and incident dementia in diverse US adults of the Northern Manhattan Study
Authors: Elfassy Tali , Gardener Hannah , Gutierrez Jose , Agudelo Christian , Wright Clinton B. , Elkind Mitchell S.V. , Levin Bonnie , Rundek Tatjana 
Published: January 2025

AbstractBackgroundThe American Heart Association’s Life Essential 8 (LE8) are a set of eight simple health metrics used to define cardiovascular (CV) health and promote healthy behaviors. High CV health is associated with a lower risk of CV disease. Our objective is to determine whether LE8 and CV health are associated with incident dementia in diverse adults.MethodsWe used data from 877 participants of the Northern Manhattan Stroke study, a population based multi racial/ethnic cohort of adults age 40 and older. Information was collected on behavioral factors (diet, smoking status, physical activity, sleep duration) and clinical factors (BMI, blood pressure, cholesterol, fasting glucose, and medication use) which were measured and used to estimate a LE8 score (range: 0 to 100). CV health was defined as low (LE8 < 50), moderate (50<LE8≤80) or high (LE8≥ 80). Incident dementia was adjudicated during follow‐up by neuropsychological assessments. We used logistic regression analyses to assess the association between LE8 and CV health with incident dementia adjusting for age, sex, race/ethnicity, and education.ResultsMean age in the sample was 64 (SD: 8.2), 59.9% were female, 15.4% were non‐Hispanic White, 17.8% were non‐Hispanic Black, and 64.7% were Hispanic. Mean LE8 was 60.8 (SD: 12.4) and 18% had low CV health, 78.9% had moderate CV health, and 6.0% had high CV health. Over an average of 8.9 years of follow‐up, 145 people developed dementia. From multivariable adjusted models, each 10 unit decrement (worse LE8 score) was associated with a 19% higher odds of developing dementia (OR: 1.19, 95% CI: 1.02, 1.40). Compared with high CV health, odds of dementia was greater by 203% among those with low CV health (RR: 3.03, 95% CI: 1.07, 8.56), but not among people with moderate CV health (OR: 1.46, 95% CI: 0.55, 3.93).ConclusionOnly 1 in 20 adults in the study had high CV health. Poor CV health defined by the new LE8 metric substantially increases risk for developing dementia. Our results show that improvements in CV health factors are critical for prevention of dementia and further studies on health metrics are warranted.
Influence of biological sex on early cognitive performance in FTLD mutation carriers: an ALLFTD study
Authors: Castro Jesús Garcia , Rubio‐Guerra Sara , González Judit Selma , Memel Molly B , Dols‐Icardo Oriol , Bejanin Alexandre , Belbin Olivia , Fortea Juan , Alcolea Daniel , Carmona‐Iragui Maria , Barroeta Isabel , Santos‐Santos Miguel A , Sánchez‐Saudinós Mª Belen , Sala Isabel , Heuer Hilary W. , Staffaroni Adam M. , Casaletto Kaitlin B. , Boeve Brad F. , Boxer Adam L. , Rosen Howard J. , Lleo Alberto , Illán‐Gala Ignacio 
Published: January 2025

AbstractBackgroundAccumulating evidence indicates that biological sex may influence clinical manifestation within the spectrum of frontotemporal lobar degeneration (FTLD), implying differences in cognitive reserve. Nonetheless, investigations into the impact of biological sex during the preclinical and minimally symptomatic stages of FTLD are lacking.MethodWe included 275 mutation carriers (158 females; 127 with C9orf72, 68 with GRN, and 80 with MAPT mutations) and 161 non‐carrier familial controls (97 females) from the ALLFTD Consortium (Staffaroni et al., Nat Medicine 2022). Participants underwent magnetic resonance imaging (MRI; 348 baseline, 338 longitudinal) and neuropsychological evaluations (394 baseline, 507 longitudinal). Behavioral symptoms were characterized with the Revised Self‐Monitoring Scale (RSMS) and the Neuropsychiatric Inventory (NPI severity scores). MRI‐derived regional volume estimates (RVE) were computed. Cognitive measures and RVE were normalized against sex‐matched controls. Cognitive composites (language, executive function, and visuospatial function) were calculated by averaging raw scores for each domain. Clinical characteristics and RVE comparisons were made between male and female participants. We adopted the residuals approach to explore behavioral and cognitive reserve by fitting a linear regression model for executive z‐scores as the response value and age, education, and RVE as explanatory variables.ResultIn mutation carriers, sex was not a significant differentiator in age, education level, disease severity, or mutation frequency. Most mutation carriers (188, 68%) were asymptomatic or mildly symptomatic at baseline. However, female mutation carriers exhibited significantly lower visuospatial performance at baseline (Cohen's d = ‐0.34, 95% CI[‐0.58, ‐0.09], p=.001). This difference remained significant among asymptomatic GRN mutation carriers (Cohen’s d = ‐0.73, 95% CI[‐1.22, ‐0.23], p=0.003) but not in other mutations. Following the residuals approach, female mutation carriers showed higher executive performance than males for the same amount of both frontotemporal and global atrophy as quantified by RVE (Cohen's d=0.45, 95 % CI[0.22, 0.67], p<.001). The observed higher executive reserve in women was particularly pronounced in C9orf72 carriers (Cohen's d=0.77, 95% CI[0.35, 1.20], p<.001) but not significant in GRN (p=0.48) and MAPT carriers (p=0.07). No differences in behavioral reserve reached statistical significance.ConclusionFemale sex might modulate early cognitive performance and confer higher executive reserve in FTLD mutation carriers.