bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unraveling Vascular and Parenchymal Microenvironment Changes in Patients with Mixed CAA/AD Pathology: A Spatial Transcriptomic In‐Depth Analysis
Authors: Juarez Enrique Chimal , Garfe Nur Jury , Redding Javier , Troncoso Juan C , Johnson Travis S , Reeves Cristian A Lasagna 
Published: January 2025

AbstractBackgroundCerebral amyloid angiopathy (CAA), defined as the accumulation of amyloid in cerebral blood vessels causing alterations in the blood brain barrier (BBB) and the gliovascular unit, occurs in over 85% of Alzheimer’s disease (AD) cases, positioning CAA as one of the strongest vascular contributors to age‐related cognitive decline. However, the specific mechanisms in the microvasculature that become altered due to amyloid deposition and its downstream effects on the brain are complex and incompletely understood. A spatial transcriptomic analysis comparing pathways affected in the gliovascular niche differently in the presence of vascular amyloid could provide critical insight into the mechanisms underlying cerebrovascular changes involved in the deposition of Amyloid in the cerebrovasculature.MethodUsing NanoString’s GeoMx Human Whole Transcriptome Atlas, which measures over 18,000 protein‐coding genes at each region of interest (ROI) in tissue sections, we evaluated mixed CAA/AD pathology patients. We evaluated and performed selected pair wise comparisons between 4 types of ROI:
1)
Astrocytes surrounding vascular amyloid,
2)
astrocytes surrounding amyloid‐free vasculature,
3)
astrocytes surrounding parenchymal amyloid, &
4)
astrocytes in an amyloid‐free parenchymal zone.ResultConducting pairwise comparisons among the four types of Regions of Interest (ROIs) unveiled distinctive transcriptomic signatures across ROI categories. Notably, gene expression profiles in regions of vasculature positive for Aβ‐amyloid differed significantly from those in amyloid‐free vasculature, showcasing pronounced gene expression changes. While the signatures corresponding to both Parenchymal amyloid and vascular amyloid have a similar transcriptional signature, they differ in certain pathways. Through meticulous data mining, we identified a co‐expression cluster of genes intricately linked to vascular amyloid deposition. Further analysis involved determining Differentially Expressed Genes (DEGs) based on ROI types, yielding a comprehensive list of potential targets indicative of the perturbations induced by vascular amyloid deposition versus parenchymal amyloid deposition.ConclusionIn summary, the identified differential (parenchymal vs vascular) genes underscore a clear association with alterations in the neurovascular microenvironment, indicating a discernible shift in vasculature dynamics attributed to amyloid presence. This observation emphasizes the significance of comprehending the changes within the vascular unit to address Cerebral Amyloid Angiopathy (CAA) thoroughly to develop comprehensive strategies to tackle CAA‐related challenges.
Neuropsychiatric symptoms and brain aging in mild cognitive impairment and early dementia: A multicenter study
Authors: Sone Daichi , Beheshti Iman , Tagai Kenji , Kameyama Hiroshi , Takasaki Emi , Kashibayashi Tetsuo , Takahashi Ryuichi , Ishii Kazunari , Kanemoto Hideki , Ikeda Manabu , Shigeta Masahiro , Shinagawa Shunichiro , Kazui Hiroaki 
Published: January 2025

AbstractBackgroundDespite the clinical importance and significant social burden of neuropsychiatric symptoms (NPS) in dementia, the underlying neurobiological mechanism remains poorly understood. Recently, neuroimaging‐derived brain‐age estimation by machine‐learning analysis has shown promise as an individual‐level biomarker. We investigated the relationship between NPS and brain‐age in amnestic mild cognitive impairment (MCI) and early dementia.MethodClinical data, including neuropsychiatric inventory (NPI), and structural brain MRI of 499 individuals with clinical diagnoses of amnestic MCI (N = 185), early Alzheimer’s disease (AD) (N = 258) or dementia with Lewy bodies (DLB) (N = 56) were analyzed. We established a brain‐age prediction model using 694 brain structural MRI scans of healthy subjects and support vector regression model and applied it to the patients’ data. Finally, the brain predicted age difference (brain‐PAD: predicted age minus chronological age) were calculated.ResultAll clinical diagnostic groups showed significantly increased brain‐PAD, and the median (IQR) brain‐PAD was 4.3 (5.4) years in MCI, 6.3 (6.2) years in AD, and 5.0 (6.5) years in DLB. The NPI scores were subdivided into the following four categories: (i) Agitation and Irritability, (ii) Depression and Apathy, (iii) Delusions and Hallucinations, and (iv) Euphoria and Disinhibition. We found a significantly positive correlation between brain‐PAD and the depression/apathy factor (Spearman’s rs = 0.156, FDR‐corrected p = 0.002), while no significance was shown in the other NPS factors.ConclusionAbnormal brain aging may be involved in depression and apathy symptoms presented in MCI to early dementia stages, and brain‐age analysis may be useful as a novel biomarker for assessment or monitoring of NPS.
Study on the correlation between leisure activities and cognitive impairment in middle‐aged and elderly people in High‐altitude environment
Authors: Zhu Aiqin , Chai Changbiao 
Published: January 2025

AbstractBackgroundTo explore the influence of leisure activities on cognitive function of middle‐aged and elderly people living in hypoxia environment.MethodUsing a cross‐sectional random sampling survey method, a total of people over 50 years old who have lived for more than 20 years (average altitude 3000m) in Qinghai plateau region were selected. Demography information, chronic medical history, economic and marital status, and 21 leisure activities (including entertainment, mobile phone use, games, sports, travel, social interaction and housework) were investigated. Cognitive domain assessment tool was from Beijing aging brain rejuvenation initiative (BABRI) Dementia Risk Assessment program.ResultAmong the 500 cases studied, there were 193 cases of cognitive impairment (CI) (38.6%), including 110 (22%) mild cognitive impairment and 83 (16.6%) Alzheimer’s disease. The CI group showed a significant increase in women, older age, workers and farmers, lower education, divorce and widowhood, living alone/with children, lower monthly income, smokers and drinkers (P<0.05); while reading (newspapers, magazines and books), playing chess and card activities (chess, poker and mahjong), watching TV, using mobile phones (Tiktok, Kwai and chatting), performing aerobic (walking, jogging, cycling and swimming) and resistance exercise (dumbbells, sandbags and pullers), traveling, visiting friends /relatives significantly decreased compared with the normal cognitive group (P<0.05). Multivariate binary regression analysis showed that women (OR = 1.787, 95% CI = 1.137‐2.808, P = 0.012), advanced age (OR = 1.066, 95% CI = 1.040‐1.093, P<0.001), occupation as workers (OR = 2.640, 95% CI = 1.263‐5.519, P = 0.010), and farming (OR = 2.420, 95% CI = 1.351‐4.333, P = 0.003) were risk factors for CI. Living with a spouse (OR = 0.211, 95% CI = 0.081‐0.548, P<0.001) and stop drinking (OR = 0.275, 95% CI = 0.093‐0.813, P = 0.020) were protective factors for CI. In leisure activities, aerobic endurance exercise (OR = 0.811, 95%CI = 0.676 ‐0.973, P = 0.024) and resistance exercise (OR = 0.625, 95%CI = 0.442 ‐0.883, P = 0.008) were protective factors for CI, while mobile phone use (OR = 1.185, 95% CI = 1.003‐1.339, P = 0.046) is a risk factor for CI. Mobile phone use (OR = 1.185, 95% CI = 1.003‐1.339, P = 0.046) was a risk factor for CI.ConclusionAerobic and resistance exercise have a protective effect on cognitive function, while long‐term mobile phone watching Tiktok, Kwai and chatting may lead to CI in middle‐aged and elderly people in hypoxia environment.
Comparing Dual and Single‐Task Postural Performance in Older Adults with a Fall‐Related Chronic Mild Traumatic Brain Injury
Authors: Sommer Amaya , Okrah Albert K , Parada Stephen A , Jirau‐Rosaly Wanda D , Bursey Max , Reynolds Bradford , Ohamadike Chijioke , Jehu Deborah A 
Published: January 2025

AbstractBackgroundFall‐related mild traumatic brain injuries (mTBI) are prevalent among older adults and are a predictor of dementia. Delays in diagnoses lead to prolonged symptoms and impairments. Dual‐task posture may be more sensitive to detecting impairments compared to single‐task posture, but research is limited. The objective of this study was to characterize single and dual‐task postural performance in older adults with a fall‐related chronic mTBI.MethodsWe included community‐dwelling older adults who were seeking medical attention and/or still experiencing ongoing symptoms of a fall‐related chronic mTBI in this cross‐sectional study (n = 3; Age: 68.6 ± 8.1 years, Montreal Cognitive Assessment = 23 points, 67% Female). Dementia was an exclusion criterion. Participants stood on an AMTI force platform for 60 seconds and completed two repetitions of single‐tasks (standing with feet apart) and dual‐tasks (standing with feet apart while silently counting backwards by 3’s). Variables assessed were the 95% confidence area (m2), center of pressure (COP) path length (m), COP velocity (m/s), and mean frequency (Hz). A two‐way Condition (single, dual) by Measure (95% confidence area, COP path length, COP velocity, mean frequency) repeated measures analysis of variance was performed to compare single and dual‐task postural performance.ResultsThere was a significant Condition by Measure interaction (F(3,6) = 11.53, p<0.01, ηp
2 = 0.85). Post hoc comparisons revealed a trend for greater path length (t(2) = ‐3.38, p = 0.08; single‐task: 0.80 m, dual‐task = 0.84 m) and velocity (t(2) = ‐3.38, p = 0.08; single‐task: 0.133 m/s, dual‐task = 0.139 m/s) during dual‐tasking compared to single‐tasking. No differences were shown in the 95% confidence area or mean frequency (p>0.05).ConclusionThe trend towards greater COP path length and COP velocity during dual tasking highlights that increased attention demand likely provokes postural instability. These measures may be sensitive to detecting impairments in dual‐task postural control; however, these findings will be confirmed as we enroll further participants in this ongoing study. Refined screening protocols for fall‐related mTBIs may the improve time to diagnosis, prevent reinjury, and mitigate long‐term impairments, including the potential onset of dementia. Future research is needed to determine if cognitive impairment is a risk factor for fall‐related mTBIs in older adults, as all our participants had mild cognitive impairment.
Baseline regional amyloid distribution in relation to subsequent self‐ and informant‐rated apathy scores in community‐dwelling older adults
Authors: Munro Catherine E 
Published: January 2025

AbstractBackgroundApathy is a common neuropsychiatric symptom of Alzheimer’s disease (AD) and has been linked to greater levels of AD biomarkers (i.e., global cortical amyloid burden and regional tau levels) in preclinical individuals. However, it is unclear whether there are regional influences of amyloid on these relationships and if these relationships differ between self‐ and informant‐rated apathy. We sought to examine whether initial baseline levels of amyloid in brain regions linked to apathy in AD could predict self‐ and informant‐rated apathy at follow‐up.Method202 participants who were cognitively unimpaired and nondepressed at baseline (mean age = 72.6) were included from the longitudinal Harvard Aging Brain Study cohort. MRI/PiB‐PET were performed at baseline and self‐ and informant‐rated apathy levels were obtained cross‐sectionally using Apathy Evaluation Scale (AES; lower scores indicating greater apathy) scores at their most recent visit (mean years follow‐up = 7.8). Regional PiB DVR values were calculated using FreeSurfer‐defined bilateral regions of interest (ROI) implicated in apathy: inferior temporal (IT), entorhinal, anterior cingulate (ACC), precuneus, supramarginal, and medial and lateral orbitofrontal (mOFC, lOFC) cortices, and the thalamus and amygdala. Separate linear regression models assessed whether regional baseline PiB levels predicted self‐ and informant‐rated apathy at follow‐up for each ROI, covarying for age, sex, education, and time‐to‐follow‐up, adjusted for multiple comparisons.ResultHigher baseline PiB levels in the IT, precuneus, supramarginal, ACC, and mOFC were associated with lower informant‐rated AES scores (indicating greater apathy) at follow‐up (Figure 1). Baseline PiB levels in any ROIs were not predictive of future self‐rated AES scores (Table 1). Results lost significance when examining only individuals who had a Clinical Dementia Rating score of 0 at follow‐up, indicating results were driven by those who progressed to cognitive impairment.ConclusionIn a cohort of older adults who were cognitively unimpaired and nondepressed at baseline, higher initial cortical amyloid levels in the IT, precuneus, supramarginal, ACC, and mOFC regions were associated with greater informant‐rated, but not self‐rated, apathy approximately 8 years later. These results shed light on the neurobiology of apathy in older individuals and preclinical AD and emphasize the importance of obtaining both self‐ and informant‐report when assessing new or worsening neuropsychiatric symptoms.
Associations among mild behavioral impairment symptoms, brain pathology and cognition in individuals with autosomal‐dominant Alzheimer’s disease: Findings from the Colombia‐Boston (COLBOS) biomarker study
Authors: Vasquez Daniel , Aguillon David Fernando , Baena Ana Y , Langella Stephanie , Munera Diana , Zubiri Victoria , Ramos Claudia , Alvarez Sergio , Ochoa‐Escudero Martin , Kaplan Elizabeth , McDowell Celina F. Pluim , Martinez Jairo E. , Giudicessi Averi , Badillo‐Cabrera Alex L , Félix Nikole A Bonillas , Vila‐Castelar Clara , Gomez Liliana A Ramirez , Lopera Francisco , Gatchel Jennifer R. , Quiroz Yakeel T. 
Published: January 2025

AbstractBackgroundNeuropsychiatric symptoms (NPS) are common in early stages of Alzheimer’s disease (AD) and may be early markers of cognitive decline and dementia in older individuals. The Mild Behavioral Impairment Checklist (MBI‐C) was developed to capture new‐onset transdiagnostic NPS in individuals at risk of dementia. We sought to determine whether mild behavioral impairment symptoms are elevated in non‐demented Presenilin‐1 (PSEN1) E280A carriers, who are genetically determined to develop dementia by their 50s. We hypothesized that those with higher MBI‐C total scores would have worse memory performance and greater brain pathology.MethodA total of 25 mutation carriers (mean age = 36.3±7.23; 56% females; 18 cognitively‐unimpaired, 7 impaired) and 30 non‐carriers (70% females) from the Colombia‐Boston (COLBOS) Biomarker study were included. All participants completed cognitive testing, the MBI‐C (self‐reported), and florbetapir (amyloid), flortaucipir (tau) PET, and structural magnetic resonance imaging. We used Mann‐Whitney Test to examine group differences, and Spearman’s correlation and linear regression to examine associations among MBI‐C total score, Geriatric Depression Scale‐15 (GDS), Mini‐Mental State Examination (MMSE), CERAD word list learning delayed recall, cortical amyloid burden, regional tau, and hippocampal volume. In sensitivity analyses, we restricted carriers to the 18 unimpaired.ResultMBI‐C total scores were similar between carriers and non‐carriers (p = 0.09). Compared to non‐carriers, carriers had greater amyloid burden (r = 0.55; p = 0.004) and lower hippocampal volume (r = ‐0.43; p = 0.034). Among all carriers, higher MBI‐C total scores were associated with lower hippocampal volume (r = ‐0.44; p = 0.034), greater amyloid burden (r = 0.5; p = 0.011), and worst memory performance (r = ‐0.36; p = 0.021). There were no associations with tau pathology (p‐values>0.05). Sensitivity analyses were consistent with previous results except for hippocampal volume (r = ‐0.4; p = 0.08).ConclusionFindings suggest that NPS captured by MBI‐C are associated with pathology and memory in a Colombian kindred with autosomal dominant AD, years before the median age of dementia onset in this cohort. This underscores the importance of behavioral symptoms in preclinical and prodromal ADAD. Follow‐up analyses with larger samples and longitudinal assessments are needed to characterize neuropsychiatric symptom evolution as an early marker and target for intervention.
Subjective Cognitive Decline‐Plus: Longitudinal Assessment and Risk for Cognitive Impairment
Authors: Kang Moonil , Li Clara , Mahajan Arnav , Spat‐Lemus Jessica , Durape Shruti , Chen Jiachen , Gurnani Ashita S. , Devine Sherral A. , Auerbach Sanford H. , Ang Ting Fang Alvin , Sherva Richard , Qiu Wei Qiao , Lunetta Kathryn L. , Au Rhoda , Farrer Lindsay A. , Mez Jesse 
Published: January 2025

AbstractBackgroundSubjective cognitive decline (SCD) is recognized to be in the Alzheimer’s disease (AD) cognitive continuum. An international working group known as the SCD‐initiative recently proposed “SCD plus” features, including report of memory problems, recent SCD relative to conversion, SCD over age 60, and consistent SCD over time, that increase the risk for future objective cognitive decline. These have not been fully assessed in a large community‐based setting.MethodParticipants from all cohorts of the Framingham Heart Study who were ≥ 60 years with normal cognition at analytic baseline were included. SCD was assessed longitudinally using a single question. We treated SCD as a time‐varying variable and considered SCD to be present if it was endorsed at the last cognitively normal visit. If SCD was endorsed during two or more consecutive visits, including the last valid visit, it was considered to begin at the first of the consecutive visits. Outcomes included consensus‐diagnosed mild cognitive impairment (MCI), AD, and all‐cause dementia. Survival analyses were performed on time‐to‐event data obtained between 2005 and 2019 with up to 12 years of follow‐up. Models were adjusted for baseline age, sex, education, APOE ε4 status, and tertiles of AD polygenic risk score (PRS) excluding the APOE region.Result3,735 participants (mean baseline age: 68.0 years, women: 55.1%, non‐Hispanic Whites: 91.6%, SCD: 44.5%, APOE ε4 carriers: 21.5%) were included. On average, SCD preceded MCI by 4.4 years, AD by 6.8 years, and all‐cause dementia by 6.9 years. APOE ε4 and tertiles of AD PRS status did not significantly differ between SCD and non‐SCD groups. SCD was significantly associated with survival time to MCI (HR = 1.57; 95% CI = 1.22−2.03; P = 4.79×10−4), AD (HR = 2.98; 95% CI = 1.89−4.70; P = 2.80×10−6), and all‐cause dementia (HR = 2.14; 95% CI = 1.44−3.18; P = 1.82×10−4). After adjustment for APOE and AD PRS, the effects of SCD were largely unchanged.ConclusionIn a community setting, SCD reflecting “SCD plus” features increased the risk of future MCI, AD, and all‐cause dementia with about the same HR estimated in clinic‐based settings. SCD may be an independent clinically expressed risk factor for preclinical AD and other dementias beyond the risk incurred by APOE ε4 and AD PRS.
Association of CSF AD biomakers and lifestyle factors with neuropsychiatric symptoms among non‐demented older persons
Authors: Soldan Anja , Truesdell Valerie , Pettigrew Corinne , Moghekar Abhay , Zipunnikov Vadim , Spira Adam P. , Albert Marilyn S. ,   BIOCARD RESEARCH TEAM
Published: January 2025

AbstractBackgroundHigher level of cognitive reserve (CR), measured using proxies such as years of education or literacy, is associated with reduced risk of Mild Cognitive Impairment (MCI) and dementia. Little is known about how CR and other lifestyle factors impact non‐cognitive outcomes, including depression and other neuropsychiatric symptoms (e.g., agitation, delusions, anxiety, etc.). This study examined whether factors that influence cognition among non‐demented older adults (i.e., CR, demographics, vascular risk, sleep quality, physical activity, ApoE4 genetic status) are also associated with depression and other neuropsychiatric symptoms, and whether these associations vary by AD pathology levels.MethodDepression and other neuropsychiatric symptoms were assessed using the Geriatric Depression Scale (GDS) and Neuropsychiatric Inventory (NPI), among 181 non‐demented BIOCARD Study participants (mean age = 72.6y, including 152 cognitively unimpaired and 29 with MCI). Total volume of physical activity and sleep efficiency were measured using actigraphy. Level of CR was based on a composite of years of education, vocabulary, and reading ability. A subset of participants (n = 125) had cerebrospinal fluid measures of amyloid and tau (Fujirebio Lumipulse G1200 assays), with AD pathology levels summarized as the ratio of p‐tau181/(AB42/AB40). Linear regressions evaluated the cross‐sectional relationship between the risk and protective factors with total GDS and NPI scores, and interactions with AD‐pathology levels.ResultsFor depression, greater total physical activity (p<0.004) and greater sleep efficiency (p = 0.006) were associated with lower GDS scores, independent of CR, age, sex, vascular risk, and ApoE4 status, which were not associated with GDS scores. The strength of this association was reduced among participants with higher AD‐pathology levels (p<0.05 for interactions of ptau181/(Ab42/Ab40 with physical activity and sleep efficiency. For neuropsychiatric symptoms, higher CR scores were associated with lower NPI scores and this association was independent of p‐tau181/(AB42/AB40) levels, but greater among those with poor sleep efficiency and among men.ConclusionThese results suggest that level of cognitive reserve, sleep quality, and physical activity levels are associated with depression and other neuropsychiatric symptoms among non‐demented older adults. Moreover, these associations differentially depend on AD‐biomarker levels, suggesting that individualized approaches to the treatment of neuropsychiatric symptoms among older adults are likely most successful.