bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of physical activity, brain volume, and plasma biomarkers of Alzheimer’s disease: The Shanghai Aging Study
Authors: Wu Wanqing , Xiao Zhenxu , Liang Xiaoniu , Zhao Qianhua , Ding Ding 
Published: June 2023

AbstractBackgroundThis study aimed to explore the potential relationship between physical activity and brain volume as well as plasma biomarkers of Alzheimer’s disease in the Chinese population.MethodThis cross‐sectional analysis included 99 dementia‐free community‐dwelling older adults from the Shanghai Aging Study. Physical activity was assessed based on questionnaires and further transformed into metabolic equivalent values (MET‐hours). Older adults were then divided into two groups: low physical activity (≤21.0 MET‐hours) and high physical activity (>21.0 MET‐hours), based on the median of MET‐hours. Data on age, sex, years of education, and smoking status were collected through questionnaires. DNA was extracted from the blood or saliva samples to conduct apolipoprotein E (APOE) genotyping. Histories of hypertension and diabetes were confirmed by the medical records. Voxel‐based morphometry analysis was performed to quantify brain volumes. Hippocampal volume estimates were obtained using the free surfer image analysis suite. Plasma β amyloidAβ40, Aβ42, Tau, and neurofilament light (Nfl) were measured by the single‐molecule array. Multivariate linear models were used to examine the association between physical activity, brain volumes, and plasma biomarkers.ResultWe observed a significant inverse association between physical activity and the level of plasma Aβ40 (high vs. low physical activity, β = ‐17.883, r = ‐0.222, p = 0.039) and a marginally significant association between physical activity and the level of plasma Aβ42 (high vs. low physical activity, β = ‐1.394, r = ‐0.204, p = 0.058), after adjusting for age, sex, years of education, APOE ε4, smoking, hypertension, and diabetes. Physical activity displayed no significant associations with plasma Tau, Nfl as well as brain volumes.ConclusionThe protective effect of physical activity on cognition might rely on its effect on the β amyloid burden.
Measuring olfactory‐related brain region volume loss in MCI and AD using structural MRI
Authors: AlOtaibi Majed , De Marco Matteo , Venneri Annalena 
Published: June 2023

AbstractBackgroundAlzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Olfactory dysfunction can be an early alteration heralding the presence of AD. Studying the pattern of alterations in olfaction‐related brain regions might help detection of neurodegenerative diseases at an earlier stage. Objectives of this study are to assess the volume of olfactory areas associated with odour processing in healthy elderly, MCI and AD populations using structural MRI scans. To test whether there are any differences in the volume of olfactory related regions between patients and healthy controls. To determine whether there is an effect of sex on olfactory‐related brain regions’ volume loss.MethodNeurologically healthy participants aged 66‐85 (n = 95), MCI aged 58‐86 (n = 81) and mild probable AD aged 55‐88 (n = 37) participants were recruited. T1‐ weighted MRI scans acquired at 1.5T were processed using SPM12. Smoothed images were used to extract the volume of olfactory cortex, hippocampus, parahippocampus, amygdala, orbitofrontal cortex and entorhinal cortex.ResultOne‐way ANOVA analyses showed a significant reduction in all olfaction‐related brain regions (p≤0.0001). Post‐hoc multiple comparison tests showed a significant reduction in volume in the AD group in all olfaction‐related brain regions. In the MCI group, a significantly smaller volume than the healthy controls was found in four of the selected olfactory‐related brain regions (namely, hippocampus, parahippocampus, amygdala and entorhinal cortex) for the total and left volume in the female group only. Additionally in the female MCI, the volume of the right entorhinal cortex however, was also significantly smaller than that of the control group. When adjusting for MMSE, however, between group differences in all olfaction‐related brain regions were no longer significant.ConclusionThese preliminary data show a significant reduction in grey matter volume in all olfaction‐related brain regions. Grey matter volume loss in these regions appears to be a good proxy of disease severity.
Impact of MCI on testing performance in different cognitive domains
Authors: Shi Xiangrong , Reddy Priyanka M , Abdali Kulsum , Ross Sarah E , Davis Sandra , Hall James , Mallet Robert T 
Published: June 2023

AbstractBackgroundImpaired memory affects cognitive testing performance. This study examined in elderly adults the impact of mild cognitive impairment (MCI) on testing performance in different cognitive domains.MethodAfter giving their IRB‐approved written consent, 10 cognitively normal subjects (65±2 years old) and 10 patients with amnestic MCI (68±2 years old) completed the Mini‐Mental State Examination (MMSE), Digit‐Span test, California Verbal Leaning Test –2nd edition (CVLT‐II), and Trail Making Test – B version (TMT‐B). Cognitive performances of the MCI and normal groups were compared by standard t tests. ANOVA was applied to evaluate the impacts of the group and trial‐number factors on immediate Free‐Recall (FR) performance in CVLT‐II.ResultThe group MMSE scores were 24.8±0.4 in the MCI group vs 29.2±0.3 in the normal subjects (P<0.0001). The time to complete TMT‐B was prolonged markedly in the MCI (154±28 s) vs. normal (56±6 s) subjects (P = 0.007). Forward performance score in the Digit‐Span test did not differ between the groups (MCI 9.0±0.6 vs normal 8.5±0.9), although backward Digit‐Span performance was superior (P = 0.021) in the normal (7.0±0.6) vs. MCI (5.1±0.4) groups. CVLT‐II immediate FR scores improved with successive trials in both MCI and normal subjects (trial‐number factor P<0.0001). Although the FR scores from the first 2 trials did not differ between the groups, there was a significant difference appeared in the FR scores of the 3rd and the overall FR scores were appreciably lower in the MCI subjects (group factor P = 0.006). Moreover, 30‐sec Short‐Delay (S‐D) and 10‐min Long‐Delay (L‐D) FR scores were significantly lower in the MCI subjects (Table).ConclusionBoth short‐term memory and visuospatial‐executive function were significantly impaired in the MCI patients as compared with the age‐matched cognitively normal cohort. Repeated trials improve the immediate Free‐Recall in both groups. The backward Digit‐Span test was more sensitive than the forward test to detect the impairment of short‐term memory and attention in the elderly adults with MCI.
Independent contribution of ATN biomarkers for progression of amnestic mild cognitive impairment to AD on top of neuropsychological tests
Authors: Zhao Lei , Shi Lin , Luo Yishan , Mok Vincent C.T. ,   for the Alzheimer Disease Neuroimaging Initiative
Published: June 2023

AbstractBackgroundATN biomarkers (amyloid beta [A], pathologic tau [T], and neurodegeneration [N]) have been known for their predictive value of Alzheimer’s disease (AD). Here, we aimed to investigate their independent contributions to predicting progression of amnestic mild cognitive impairment (aMCI) to AD on top of neuropsychological tests.MethodWe included 496 aMCI patients with neuropsychological tests and ATN biomarkers from cerebrospinal fluid (CSF) examinations, MRI and FDG‐PET at baseline. The involved ATN biomarkers included CSF‐Aβ, CSF‐Ptau, CSF‐Tau, FDG‐PET and an MRI‐based Alzheimer’s disease resemblance atrophy index (AD‐RAI) calculated by AccuBrain IV2.0. All the demographic and neuropsychological features (Table 1) were entered into the cox model with backward elimination to predict time to AD (subscores of FAQ and ADAS‐cog also entered as candidate predictors) using training cohort (n = 330, 34.8% developed AD within 3.60±2.46 years). The resulting model was treated as the basic model. The enriched models with individual and multiple ATN biomarkers were further compared with the basic model regarding the improvement in C‐index (measuring prediction performance of time to AD) and time‐dependent AUC (t‐AUC, measuring prediction performance of time‐specific progression) in validation cohort (n = 166, 35.5% developed AD within 3.66±2.52 years).ResultThe features that survived backward elimination for the basic model were shown in Table 2. Binary form of A/T/N variables were preferred for Aβ/Tau, while continuous form preferred for Ptau/FDG‐PET/AD‐RAI (Table 3). Compared with the basic model, all the enriched models with individual A/T/N biomarkers (except for Basic+Tau) presented higher C‐index in the training cohort (p<0.05), while only Basic+(AD‐RAI) and Basic+(FDG‐PET) presented higher C‐index in the validation cohort (Table 4). Basic+(FDG‐PET) presented highest t‐AUC (0.861∼0.924) among the models with individual A/T/N biomarkers (Figure 1A). The enriched model with multiple ATN biomarkers (Aβ/Ptau/FDG‐PET/AD‐RAI) presented highest C‐index in both training and validation cohort, which also showed higher t‐AUCs (generally ≥0.90 through year 3∼7) than the models with individual A/T/N biomarkers in trend (Figure 1B). These findings indicated that multiple ATN biomarkers should be used for the optimal model (Figure 2).ConclusionATN biomarkers, when combined in use, presented most contribution to predicting aMCI‐to‐AD progression independent of demographic characteristics and neuropsychological tests.
How white matter hyperintensities impacts Alzheimer’s disease and frontotemporal dementia across underrepresented Latin American samples
Authors: Campo Cecilia Gonzalez , Fraile‐Vazquez Matias , Ibanez Agustin 
Published: June 2023

AbstractBackgroundWhite matter hyperintensities (WMH) are frequently observed on MRI scans of older people. Usually interpreted as a sign of cerebrovascular disease (CVD), they are also associated with increased risk of cognitive impairment and dementia. While WMH and CVD are highly prevalent in Alzheimer’s disease (AD), this has been less studied in behavioral variant frontotemporal dementia (bvFTD), letting alone their study in underrepresented populations with increased CVD. Here, we investigated WMH in AD and bvFTD patients in Latin America (Argentina, Chile and Colombia), a region with high prevalence of CVD. We analyzed total volume and regional distribution of WMH and its association with cognitive impairment and brain lacunes, a marker of CVD.MethodA total of 66 patients (43 AD, 23 bvFTD) and 66 controls (CN) from the ReDLat consortium underwent high‐resolution brain MRI and neuropsychological examination. WMH were extracted from Flair images using automated segmentation algorithms to perform analyses of total volume and spatial distribution. Brain lacunes were visually quantified from T1 and Flair images. Group differences in total and regional WMH volume and associations with different cognitive domains, age, and brain lacunes were examined.ResultTotal and regional WMH volumes were significant larger in AD patients compared to CN and to bvFTD. No differences were found between CN and bvFTD. Only in AD, regional WMH load correlated with worse performance in a particular executive functioning task. No differences were found in the proportion of lacunes among groups nor in the total load of WMH of subjects with or without lacunes. In CN and AD, but not FTD, there was a positive correlation between total WMH volume and age, with a differential topographic distribution with a selective involvement of the bilateral cingulum‐hippocampus bundle in AD.ConclusionEnhanced WMH was observed in AD but not in FTD. WMH loading in specific brain regions contribute to domain‐specific cognitive deficits in AD. WMH could be partially independent of vascular pathology (it was unrelated to brain lacunes) suggesting a specific neurodegenerative origin in AD. The typical earlier onset of brain abnormalities in FTD could mask the age‐related increase in WMH.
Structural integrity of the anterior mid‐cingulate cortex contributes to resilience to delirium in SuperAging
Authors: Wong Bonnie , Katsumi Yuta , Cavallari Michele , Fong Tamara G. , Alsop David C , Andreano Joseph M , Carvalho Nicole , Brickhouse Michael , Jones Richard N , Libermann Towia A , Marcantonio Edward R , Schmitt Eva M , Shafi Mouhsin , Pascual‐Leone Alvaro , Travison Thomas G , Barrett Lisa F , Inouye Sharon K. , Dickerson Brad C. , Touroutoglou Alexandra 
Published: June 2023

AbstractBackgroundIdentifying factors that confer resilience to developing delirium is critical given the negative impact of delirium on clinical care and risk for mortality. Here, we investigated a cohort of cognitively normal older adults undergoing elective surgery and examined the role of pre‐operative memory function and cortical thickness in the incidence and severity of post‐operative delirium (POD). We hypothesized that 1) those older adults with episodic memory function comparable to that of young adults (“SuperAgers" or SA) would show reduced incidence of POD compared with typically‐aging older adults (TOA) and 2) cortical thickness in the anterior mid‐cingulate cortex (aMCC), the integrity of which has been consistently associated with SuperAging, would predict reduced incidence and severity of POD.Method19 SA and 74 TOA (mean age 75.8 +/‐ 4.1; 57F/36M) completed neuropsychological testing and underwent structural brain MRI pre‐operatively as part of the Successful AGing after Elective Surgery (SAGES) Study. SA were identified based on neuropsychological criteria defined in previous studies. Delirium incidence and severity were assessed using the Confusion Assessment Method (CAM) daily throughout hospitalization. A general linear model analysis was performed to identify regions of the cerebral cortex whose thickness was associated with CAM scores.ResultsNo differences were found in age or education between SA and TOA. Remarkably, no SA developed POD; POD occurred only in the TOA group (D‐TOA = 15). Severity of POD was negatively associated with cortical thickness of bilateral aMCC. A one‐way ANOVA comparing mean aMCC thickness across subgroups revealed a significant effect (F(2,89) = 3.09, p ≤ .05), with thickness greatest in SA compared with D‐TOA (t(31) = 2.47, p ≤ .019, Cohen’s d = 0.89), but comparable compared to thickness seen in non‐delirious (ND) TOA (t(76) = 0.72, p ≤ .72, d = 0.10). Greater aMCC thickness was also observed for ND‐TOAs compared with D‐TOAs (t(71) = 2.26, p ≤ .03 d = 0.72).ConclusionThese findings suggest that superior memory function and greater structural integrity of the aMCC may be important indices of resilience to delirium in older adults that can serve as a target of preventive or therapeutic interventions.
Development of an app‐based life story intervention: Lessons learned from including persons living with dementia in focus group research
Authors: Wilk Christa , Cordell Ashlee , Orsulic‐Jeras Silvia , Powers Sara , Ejaz Farida , Sanders Beth 
Published: June 2023

AbstractBackgroundA small‐scale focus group study was conducted utilizing persons living with dementia (PLWD) to inform the development of an app‐based life story review intervention.MethodTwo (Time 1 and Time 2) 60‐minute virtual (Zoom) focus groups were conducted 9 months apart with persons living with dementia (n = 5) and facilitated by research staff. In Time 1, participants were sent in advance a series of LifeBio MemoryTM tablet‐app prototypes and asked to provide specific feedback on the following: 1) ease of use, 2) clarity of instructions, 3) feasibility to use the product, and 4) potential impact on person‐centered care practices. Time 2 presented the complete app to participants for similar feedback. To maximize successful participation, participants received one‐on‐one support by research staff prior to focus groups. Assistance was provided with using Zoom and navigating the tablet and LifeBio MemoryTM prototype and app. Dementia‐friendly materials were created for participants. Research staff conducted a thematic analysis of all transcripts. Time 1 findings were utilized to inform product development based on PLWD‐specific feedback; Time 2 findings were utilized for product refinement.ResultAlthough the PLWD sample was small, promising acceptability and feasibility findings were reported. All 5 PLWD participated in Time 1 and Time 2 focus groups. Themes from Time 1 (prototype) findings included: 1) Comfort using app‐based product technology, 2) Value of sharing their life story, 3) Training issues, 4) Implementation concerns, and 5) Concerns with how PLWD are perceived. PLWD feedback, was integrated in the development of the product. Analysis of Time 2 determined: 1) Some remaining training concerns, 2) High levels of satisfaction, and 3) Buy‐in that a product like LifeBio MemoryTM can impact person‐centered care. Themes, recommendations, and action steps were proposed and changes were made in content and functionality, in preparation for an upcoming feasibility study to test the LifeBio MemoryTM app with PLWDs living in residential care (n = 242).ConclusionBy building in supports, persons living with dementia are able to successfully participate as members of a research team, providing valuable feedback as stakeholders in product development research; further, virtual delivery of focus groups is also possible.
Asian Americans and Pacific Islanders’ preferences in recruitment strategies/messaging for participation in a research recruitment registry for Alzheimer’s disease and related dementias, aging, and caregiving research: A discrete choice experiment survey
Authors: Park Van Ta , Grill Joshua D. , Ameli Niloufar , Helman Sarit , Tzuang Marian , Tsoh Janice Y. , Meyer Oanh L. , Nam Bora , Hinton Ladson , Kanaya Alka , Gallagher‐Thompson Dolores , Vuong Quyen , Bang Joon , Shin Hye‐Won , Gansky Stuart 
Published: June 2023

AbstractBackgroundUnderrepresentation of Asian Americans and Pacific Islanders (AAPIs) in research requires urgent attention. The Collaborative Approach for AAPIs Research and Education (CARE) registry aims to increase AAPIs’ representation in research. We report results from a multilingual discrete choice experiment (DCE), an innovative method to determine older AAPIs’ preferences for tailored recruitment strategies and messaging.MethodsInitial DCE recruitment strategy/messaging attributes and attribute levels were selected based on feedback from CARE focus groups. A pilot study (16 participants from 7 AAPI cultural groups) refined attribute wording and levels. The final DCE survey was translated into Simplified and Traditional Chinese, Korean, and Vietnamese. CARE academic and community partners recruited participants (AAPIs aged ≥50 years) for the survey, asking them to select their preference in each of 12 pairs of recruitment strategies (randomly selected from 48 different combinations) of three attributes: (1) from whom they would like to learn about CARE; (2) what would motivate them to join CARE; and (3) how they would prefer hearing about CARE. A custom Qualtrics survey displayed image pairs of randomly selected messaging combinations. Analyses utilized conditional logistic regression models to estimate odds ratios with 95% confidence intervals.ResultsA total of 356 (mean age = 65.0; range: 50‐93) participants from 7 AAPI cultural groups (Asian Indian, Chinese, Filipino, Japanese, Korean, Samoan, and Vietnamese) completed the survey. Overall, participants had similar preferences for learning about CARE between community organizations and the healthcare community, however, participants preferred learning about CARE from the healthcare community (e.g., doctors, clinics) relative to community champions and faith‐based organizations. Participants were more motivated to join CARE to help advance research relative to sharing personal experiences; and preferred to hear about CARE via social media and instant messaging relative to a flyer or workshop/seminar. Importantly, preferences varied by age, cultural group, survey completion language, and whether the participant received assistance with the survey.ConclusionsTo our knowledge, this is the first study using a DCE approach to elicit preferences for registry recruitment strategies among AAPIs. Findings will inform appropriate tailoring of recruitment strategies/messaging to successfully engage AAPI participants in a registry for ADRD research.aging after age 90.
Association of motor function with cognitive trajectories, risk of mild cognitive impairment, and structural brain differences
Authors: Wang Zhangyu , Yang Wenzhe , Li Xuerui , Dove Abigail , Qi Xiuying , Bennett David A , Xu Weili 
Published: June 2023

AbstractBackgroundThe impact of motor function (MF) on cognitive trajectories and mild cognitive impairment (MCI) remains unclear. This study aimed to examine the association of MF with cognitive trajectories, risk of MCI, and structural brain differences on magnetic resonance imaging (MRI).MethodWithin the Rush Memory and Aging Project, 1,216 cognitively intact participants (mean age: 78.60±7.25 years) were followed for up to 22 years. Baseline global MF was assessed by averaging the z‐scores of 10 motor tests and categorizing these scores tertiles (low middle, and high). Global and domain‐specific cognitive functions – including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed – were assessed annually through 19 cognitive tests. Incident MCI was detected and diagnosed based on standard criteria. A subsample (n = 284) underwent brain MRI and regional structural brain volumes were measured. Data were analyzed using linear mixed‐effects models, Cox regression, and linear regression.ResultAt baseline, global MF scores ranged from 0.46 to 1.82 (mean score: 1.06 ± 0.22). During the follow‐up (median, 6.98 years; interquartile range, 3.08‐10.75 years), 553 participants (45.48%) developed MCI. Compared to participants with high MF, those with low MF had faster decline in global cognition (β = ‐0.05, 95% confidence interval [CI]: ‐0.06 to ‐0.03), episodic memory (β = ‐0.05, 95% CI: ‐0.07 to ‐0.03), semantic memory (β = ‐0.04, 95% CI: ‐0.05 to ‐0.02), working memory (β = ‐0.04, 95% CI: ‐0.05 to ‐0.03), visuospatial ability (β = ‐0.03, 95% CI: ‐0.04 to ‐0.02), and perceptual speed (β = ‐0.04, 95% CI: ‐0.06 to ‐0.03) over the follow‐up. The multi‐adjusted hazard ratio (95% CI) of MCI was 1.84 (1.41 to 2.42) for the lowest MF tertile compared to the highest. Furthermore, the low MF was related to a significantly greater volume of white matter hyperintensities (β = 0.16, 95% CI: 0.01 to 0.32), but not total brain, white matter, or gray matter volumes (all P >0.05).ConclusionLow MF is associated with faster cognitive decline (including episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed) and a moderately increased risk of MCI. Vascular pathologies might play an important role in the MF‐MCI association.