bluuebunny/crossref_metadata_2025_split huggingface dataset:
NEUROPROTECTIVE ACTIVITY OF MICHELIA CHAMPACA AGAINST ALZHEIMER’S DISEASE IN RAT MODEL
Authors: Anawal Lingaraj , M Chandrashekhar V , Shalavadi Mallappa , M Chandrashekhar V 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is one of the neurodegenerative disease characterized by progressive loss of memory, thinking skills, language and other cognitive functions. The main objective of this work is to investigate neuroprotective activity of Michelia champaca against Alzheimer’s disease.MethodNeuroprotective activity was carried out by colchicine induced Alzheimer’s disease on Sprague‐Dawley rats. Test group animals administrated with Ethanol extract Michelia champaca at dose of 200, 400, and 600mg/kg for 28 days. The Behavioural parameters were assessed using the Morris water maze test, Spontaneous locomotor activity using Open field Apparatus and Plus maze were performed at Days 0, 7, 14 and 28 on intracerebroventricular administration of colchicine for assessing the cognitive and gross behavioural activities in all groups. Biochemical parameter such as lipid peroxidation, glutathione, superoxide dismutase, catalase, total thiols and acetylcholinesterase were assessed and histopathology of brain tissue was assessed on the final day of the experiment.ResultEthanol extract of Michelia champaca shows a dose dependent neuroprotective activity by significant decrease in time latency of Morris water maze (p<0.001), Plus maze (p<0.001) increase in the Spontaneous locomotor activity (p<0.001) in EMC treated group compared to colchicine induced control group. Biochemical parameters showed significant decreases in lipid peroxidation (p<0.001) and increased in superoxide dismutase (p<0.001) catalase (p<0.001) glutathione (p<0.001) total thiols (p<0.001) and acetylcholinesterase level (p<0.001) in the EAM treated groups as compared with colchicine induced control group.ConclusionIn conclusion, the present study suggests that administration of ethanol extract of Michelia champaca (EMC) possesses neuroprotective activity against colchicine induced cognitive impairment and associated oxidative stress.
Unique CSF lipid signature in asymptomatic subjects with a parental history of Alzheimer’s disease and its association with key apolipoprotein species
Authors: Labonté Anne , Picard Cynthia , Poirier Judes , Group Prevent‐AD Research 
Published: December 2023

AbstractBackgroundCSF apolipoproteins exhibit lipid‐specific relationships (signatures) with Alzheimer’s disease (AD) pathological markers and APOE‐ε4 in asymptomatic individuals.MethodMass spectrometry‐based CSF lipid analysis was performed as described before (Sampaio et al. 2011). Lipids were extracted using a one‐step chloroform/methanol procedure. After extraction, resulting samples were analyzed by direct infusion on a QExactive mass spectrometer equipped with a TriVersa NanoMate ion source. Both MS and MSMS data were combined to monitor CE, DAG and TAG ions as ammonium adducts; PC, PC O‐, as acetate adducts; and CL, PA, PE, PE O‐, PG and PI as deprotonated anions. CSF levels of amyloid beta (Aβ42), and total Tau (t‐Tau) were measured by enzyme‐linked immunosorbent assay (Fujirebio, Sweden) whereas apolipoproteins (AI, AII, B, CI, CII, CIII, D, E and J) concentrations were assessed using the Luminex/Biorad assays kit (10‐plex magneto‐fluorescent immunoassays, BioRad, USA).ResultsTo characterize human CSF lipid signatures and their relationship to several apolipoproteins in pre‐symptomatic AD, we profiled and analyzed 21 classes of lipid species (for a total of 796 sub‐species) and 10 apolipoproteins in 120 cognitively unaffected subjects exhibiting various levels of total tau, p(181)tau and Aβ42. Figure 1 illustrates the signature profile (after FDR correction) following stratification by APOE‐ε4 genotype at the time of recruitment, when no cognitive deficit was detected. Please note the preferential associations between phosphatidylethanolamine acetate species and apoB levels in the CSF in non‐ε4 carrier. The apoD‐lipid signature profile was found to be very different in ε4 versus non‐ε4 carriers. Figure 2 illustrates the different associations between lipid species and the different apolipoproteins found in the CSF as a function of AD severity (stratified using the CSF T‐Tau/Aβ42 ratio). As ratio increases (top tertile) and pathology unfolds, the lipid signatures become markedly altered, with strong effects observed with apoB, apoD and apoJ interactions.ConclusionOur results suggest that early amyloid and tau pathologies modulate the release of specific lipid species in the CSF which alters their relationship with apolipoproteins in an APOE‐ε4‐dependent manner.
Experiences of People Living with Dementia and their Care Partners in Participating in Outdoor Activities
Authors: Tavilsup Pattara , Abolarin Margaret , Jakubec Sonya , Roach Pamela , Smith Eric E. , Goodarzi Zahra , Kirkham Julia , Ismail Zahinoor , Svrcek Clark , Seitz Dallas 
Published: December 2023

AbstractBackgroundThere is increasing evidence for non‐pharmacological interventions to prevent dementia and delay disease progression. Outdoor recreational activities, such as visits to local parks, may help improve behavioural symptoms of dementia, cognition, and quality of life for both people living with dementia (PLWD) and their care partners. However, little is currently known about the experiences of PLWD and care partners about participating in outdoor activities. Understanding their experiences will help inform interventions and policies to promote participation in outdoor activities. Our objectives are to understand the experiences of PLWD and care partners in participating in outdoor activities.MethodsWe conducted semi‐structured interviews with PLWD and care partners, either alone or in dyads. Self‐reported characteristics of PLWD and care partners were recorded by online surveys. Interviews were recorded and transcribed for analysis. Interview questions included questions about the following topics: individuals relationships to outdoor activities; how these relationships may have changed over time; their current patterns of outdoor activities; perceived benefits of outdoor activities; potential risks of outdoor activities; and facilitators and barriers to participating in activities. The transcripts of interviews were coded by two independent members of the research team to identify common themes.ResultA total of 10 participants (7 care partners; 3 PLWD) have participated in interviews to date. Themes identified from interviews include: 1.) Outdoor activities help people maintain a sense of identity and connection with their lives before being diagnosed with dementia; 2.) Both a diagnosis of dementia, stage of dementia, and physical changes associated with aging impact on the types of activities people participate in; 3.) Outdoor activities are associated with psychological benefits for PLWD and care partners; 4.) There are unique considerations for PLWD and care partners that need to be considered when designing outdoor spaces or programs for PLWD.ConclusionOutdoor activities are important to PLWD and care partners and help maintain connections to individuals' identities and are perceived as important to maintaining quality of life. The design of outdoor spaces and activities programs for PLWD and care partners need to incorporate their perspectives to maximize participation and benefits associated with outdoor activities.
Early loss of microglial p38α MAPK in the APPswe/PS1dE9 mouse model of Alzheimer’s disease alters soluble amyloid beta and reduces microglia co‐localization with amyloid plaques without affecting amyloid‐associated pathology
Authors: Frazier Hilaree N , Braun David J , Davis Verda A , Coleman Meggie J. , Rogers Colin B , Van Eldik Linda J. J. 
Published: December 2023

AbstractBackgroundThe p38 alpha mitogen‐activated protein kinase (p38α) pathway is linked to both innate and adaptive immune responses, and is currently under investigation as a target for drug development in the context of Alzheimer’s disease (AD) and other conditions with neuroinflammatory dysfunction (Asih et al., 2020). Preclinical data indicates that p38α inhibition can protect against AD‐associated neuropathology, although the cellular mechanisms and signaling pathways that underlie these effects have not been fully elucidated. Evidence suggests that inhibition of p38α may provide benefit by modulating microglial‐associated neuroinflammatory processes that contribute to the development of AD pathology. The present study tests this hypothesis by assessing early‐stage pathological changes in AD model mice following microglial‐specific knock out (KO) of p38α.MethodsKO of p38α in microglia was accomplished in 5‐month‐old C57BL/6J wild‐type and amyloidogenic AD model (APPswe/PS1dE9) mice using a tamoxifen‐inducible Cre/loxP system under control of the Cx3Cr1 promoter. Animals underwent behavioral assessment on the open field test at 7.5 months of age and on the radial arm water maze test at 11 months of age, followed by collection of cortical and hippocampal tissues. Other endpoint measures included quantification of proinflammatory cytokines, assessment of amyloid burden and plaque deposition, and characterization of microglia‐plaque dynamics using a combination of ELISA, immunohistochemical, and immunofluorescent techniques.ResultsSuppression of microglial p38α did not alter behavioral outcomes, proinflammatory cytokine levels, or overall amyloid plaque burden, but did significantly increase hippocampal levels of soluble Aβ42 and reduced hippocampal colocalization of Iba1 and 6E10 in a subset of microglia in close proximity to plaques.ConclusionThis work suggests that rather than reducing inflammation per se, microglial p38α inhibition in the context of early AD‐type amyloid pathology may alter hippocampal microglia‐plaque interactions. Additionally, these results support future investigations of microglial p38α signaling at different stages of disease, as well as the potential relationship between p38α and phagocytic processes in this particular cell‐type.
Funding: This work is supported by the National Institutes of Health (RF1 AG064859; F32 AG058456; T32 AG057461).
Impact of genetic risk in multidomain lifestyle preventive interventions
Authors: Solomon Alina 
Published: December 2023

AbstractBackgroundInteractions between genetic and lifestyle‐related risk factors for dementia have been investigated mainly in observational studies, with conflicting results. Less is known about whether genetic risk factors for dementia (not just APOE4 allele but also polygenic risk beyond APOE4) have an impact on the effects of multidomain lifestyle preventive interventions on cognition. Although there is overlap between risk factors for dementia and e.g. cardiovascular diseases (CVD), it is unclear if CVD genetic risk may also have an impact on potential intervention benefits.MethodThe FINGER randomized controlled trial included 1260 participants aged 60‐77 years and at risk for dementia from the general Finnish population. Cognition improved more during 2 years in the multidomain lifestyle intervention (diet, exercise, cognitive training, social activities and cardiovascular risk monitoring) compared with control (regular health advice) group. Genetic risk scores for Alzheimer’s disease (AD‐GRS, excluding APOE) and CVD‐GRS were selected based on existing literature, and calculated using GWAS data from FINGER participants.ResultPrevious findings indicated that the FINGER intervention had clear cognitive benefits among APOE4 carriers. Preliminary results suggested a less straightforward impact of AD‐GRS, especially after adjustment for APOE4. There seemed to be a pattern of more intervention‐related cognitive benefit among participants with lower compared with higher CVD‐GRS.ConclusionAPOE4, AD‐GRS and CVD‐GRS may have different impact on the cognitive benefits of multidomain lifestyle interventions for dementia prevention. Ongoing World‐Wide FINGERS trials in populations with a variety of genetic profiles will create opportunities for more detailed investigation of genetic‐lifestyle interactions in the context of preventive interventions.
Multi‐Trajectories of Blood Pressure and Cognitive Function in U.S. Adult Population
Authors: Xu Hanzhang , Ford Cassie , Clark Amy G , Yang Qing , Green Michael D. , Lynch Scott M. , Navar Ann Marie , Xian Ying , Peterson Eric D. , Dupre Matthew E. 
Published: December 2023

AbstractBackgroundElevated blood pressure (BP) levels are associated with cognitive impairment and the development of Alzheimer’s disease and related dementias (ADRD). However, long‐term co‐occurring changes in BP and cognitive function are poorly characterized.MethodUsing data from the 2006‐2018 Health and Retirement Study (HRS), we identified 21,968 adults aged 50 years or older without ADRD at baseline (median follow‐up 8 years). Cognitive function was measured at each wave occurred every 2 years using a summary score that included immediate/delayed word recall, serial 7’s test, objective naming test, backwards counting, recall of the current date, and naming the president/vice‐president (score range = 0‐35). BP was measured at each wave in random half samples. We used group‐based trajectory models to identify age‐based multi‐trajectories of cognitive function and both systolic and diastolic BP from age 50 to 90.ResultFour distinct co‐occurring trajectories of systolic BP and cognitive decline were identified (Figure 1): moderately‐increasing systolic BP with moderate and accelerated cognitive decline(Group 1; 34.6%; 95% CI, 33.2%‐36.0%; n = 7,600), moderately‐increasing systolic BP with high levels of cognitive function and minimal decline (Group 2; 39.6%; 38.2%‐41.0%; n = 8,699), elevated‐increasing systolic BP with low and accelerated cognitive decline (Group 3; 14.0%; 13.3%‐14.8%; n = 3,075), and high‐stable systolic BP with moderate cognitive decline (Group 4; 11.8%; 10.5%‐13.0%; n = 2,594). Findings were similar for co‐occurring trajectories of diastolic BP and cognitive decline, but changes in diastolic BP were attenuated with age. Male, White, and more highly educated were most likely to be in Group 2 than other groups. Black adults were more likely to experience elevated BP and/or accelerated cognitive decline: Black men were most likely to be in Group 3. Among women, Black race was associated with increasing likelihood of belonging to Group1 & 4.ConclusionTrajectories of systolic BP and cognitive decline varied throughout middle‐to‐late adulthood. The distinct patterns emerging that may also align with demographic differences in the prevalence of ADRD and cardiovascular risk factors. Additional research is needed to further address the underlying mechanisms contributing to age‐related changes in BP and cognitive decline.
Sex modifies the associations of regional fat with cognitive functioning and AD‐related brain volumes, in Israeli middle‐aged adults at high AD risk
Authors: Golan Sapir , Boccara Ethel , Ravona‐Springer Ramit , Inbar Yael , Zelicha Hila , Shai Iris , Livny Abigail , Bendlin Barbara B , Lesman‐Segev Orit H. , Yore Iscka , Azuri Joseph , Beeri Michal S 
Published: December 2023

AbstractBackgroundHigh body mass index (BMI) has been consistently linked to poorer cognition and higher dementia risk, with different associations in males and females. However, BMI does not represent well specific fat depots. We examined in middle‐aged adults at high Alzheimer’s dementia (AD) risk, whether regional abdominal adiposity is associated with cognitive functioning and brain indices and whether sex modifies these associations.Methods204 healthy Israeli middle‐aged AD offspring (59.44 [SD = 7.60] years old, 60% females) underwent abdominal Magnetic Resonance Imaging (MRI) to quantify hepatic, pancreatic, and peripheral fat %‐visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). A broad cognitive battery defined global cognition and specific cognitive domains (episodic memory, working memory, executive functions, and language). A subsample of 142 participants had brain MRI to assess regional brain volumes (total gray matter [GM], hippocampus, and inferior, middle, and superior frontal gyrus [IFG, MFG, and SFG, respectively]). Partial correlations examined associations of regional abdominal adiposity with cognitive functioning, and brain indices, adjusting for age, sex, education, BMI, and time interval between abdominal MRI and the dependent variable. Fisher‐z transformation compared partial correlations between males and females.ResultsIn the whole sample, the only significant association was of higher hepatic fat % with lower GM volume (r = ‐264, p = 0.003), with similar associations in males and females. Only in males, higher pancreatic fat % was associated with lower global cognitive functioning (Males: r = ‐.276, p = .028; Females: r = 0.009, p = 0.93), executive functioning (Males: r = ‐0.267, p = 0.034; Females: r = 0.015, p = 0.87) and episodic memory (Males: r = ‐0.278, p = 0.027; Females: r = 0.068, p = 0.484) as well as with lower IFG volume (Males: r = ‐0.343, p = .017; Females: r = 0.117; p = 0.326). Also only in males, higher VAT% was associated with SFG volume (Males: r = .261, p = .045; Females: r = ‐0.198; p = 0.091).ConclusionIn middle‐aged males, but not in females, at high AD risk, regional abdominal adiposity, primarily pancreatic fat, was associated with lower cognitive functioning and lower AD‐related brain volumes. Results suggest sex differences in the contributions of fat to brain and cognitive aging. Since fat % is modifiable, these results may suggest that interventions to decrease distinct fats for the advancement of brain health must be sex‐specific.
Poor Diet and Lower Neuropsychological Performance in a rural setting: The Bogalusa Heart Study
Authors: De Anda‐Duran Ileana , Potts Kaitlin S , Libon David J , Carmichael Owen T. , Bazzano Lydia 
Published: December 2023

AbstractBackgroundPoor diet has been associated with insidious onset dementia. The Alternate Healthy Eating Index (AHEI) can capture overall nutrient quality and individual/population eating behaviors. Higher adherence to AHEI has been associated with a lower risk of incident dementia and better cognitive function in late life. However, most evidence comes from high‐income populations from urban areas. Here, we examined the adherence to AHEI and its association with cognitive function in midlife among Black and White individuals from a community cohort in the rural, low SES area of Bogalusa, Louisiana.MethodThis cross‐sectional analysis considered 1,040 participants from the Bogalusa Heart Study (mean age 48.1 ± 61% female, 31% Black) with a complete neuropsychological (NP) assessment and food frequency questionnaires. (AHEI‐2010 score, range 0‐110). Regression models using GEE accounted for clustering effects of neighborhood factors/SES using census‐track level codes and estimated the association between quintiles (Q1‐Q5) of AHEI‐2010 and a global cognitive z‐score (GCS) and cognitive domains.ResultIndividuals in Q5 (healthiest) tended to be female (68%, p = 0.03), significantly older (49.3 ± 5, p<0.001), with higher education (³ college 56%, p<0.001), and AHEI‐2010 scores from 53.38‐79.2. Compared with participants in Q1. Those in Q5 had higher GCS [ß (95% CI):1.71 (0.85, 2.57); p<0.001] after adjusting for age, sex, race, and the ACS‐Index of concentration at the extremes (to account for neighborhood‐level SES). Similarly, those with the healthiest diet had higher NP z‐scores within the domains of executive function, attention and speed processing information, and episodic memory. However, these associations were not significant after adjusting for education. (Table 1) For episodic memory, individuals in quintile 4 had higher NP z‐scores after adjusting for education [0.36 (0.07, 0.65); p = 0.01], and the trend across quintiles was also significant in all models and after adjusting for education [p = 0.03].ConclusionAs early as midlife, Black and White individuals from rural settings with greater adherence to healthy dietary patterns have better NP performance across different neurocognitive domains. These results strengthen previous evidence suggesting that diet quality may be a potential avenue of intervention to prevent cognitive decline and aid health disparities.
Loneliness and Global Cognitive Functioning: A Study of Racially and Ethnically Diverse Older U.S. Adults
Authors: Camacho David , Aranda Maria P. , Reid M. Cary , Wethington Elaine R 
Published: December 2023

AbstractBackgroundFew studies have examined the association of loneliness and cognitive functioning in the U.S., and these rarely assessed whether this relationship varied by race. We assessed this association in a large sample of U.S. Black, Latino, and White adults (ages≥50).MethodWe analyzed Wave 3 of the National Social Life, Health, and Aging Project (N = 2,334). We examined loneliness via one item from the CES‐D (“Direct”) and the Felt Loneliness Measure (NFLM; “Indirect”), and cognitive functioning via the Chicago Cognitive Functioning Measure (CCFM; higher scores indicated better functioning). We used weighted generalized linear models to examine the main and interactive effects of loneliness (direct and indirect in separate models) and race on CCFM scores. We adjusted for: sociodemographic and other salient factors (e.g., chronic disease, depressive symptoms, living alone).ResultMean age was 67 years, 53.5% were female, 11.5% were Black and 8.1% Latino. 42% of sample was lonely on at least one measure; 29% (direct) and 30% (indirect). The relationship between loneliness measures was significant, X2 (1, N = 2,344) = 594.64, p = .001. However, only 40% of lonely individuals were identified as lonely on both direct and indirect assessments. Direct: loneliness was inversely (β̂ = ‐.291, p = .013) associated with CCFM scores and this association did not vary by race. Indirect: loneliness was positively associated (β̂ = 1.504, p = .001) with better CCFM scores for Latinos only.ConclusionLoneliness appears to be an important predictor of cognitive functioning. However, the association of loneliness and cognitive functioning may vary as a function of measurement and race. Further research is needed, particularly to understand the counterintuitive finding for Latinos. For example, future research should explore how different measures of loneliness (direct vs. indirect), and dimensions of loneliness (social, emotional, existential, chronicity), relate to global and individual cognitive domains. Also, research is needed to explore how diversity within groups (nativity, acculturation, migratory status), contextual (established vs. new destination states), and cultural factors (stigma, beliefs, coping) influence cross‐sectional and longitudinal relationships between loneliness and cognitive functioning. Finally, findings also support the need for research on interventions to prevent cognitive decline targeting loneliness.