bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of clinical diagnostic criteria for behavioral/dysexecutive Alzheimer’s Disease in patients presenting with mild behavioural or dysexecutive symptoms
Authors: Iacovino Najara , Tondelli Manuela , Carbone Chiara , Gallingani Chiara , Molinari Maria Angela , Chiari Annalisa , Zamboni Giovanna 
Published: January 2025

AbstractBackgroundDiagnosis in patients with Mild Behavioural Impairment (MBI) and with Mild Cognitive Impairment (MCI) with predominant executive deficits (eMCI) is often challenging, as they may be representing the early phase of both Alzheimer’s Dementia (AD) as well as behavioural variant Frontotemporal Dementia (bvFTD). If neuropathology biomarkers aren’t available, diagnosis is even more difficult. We evaluated the performance of classification of different clinical diagnostic criteria for behavioural/dysexecutive AD (without biomarkers) in MBI and eMCI.MethodConsecutive patients with a clinical diagnosis of MBI or eMCI seen in our Cognitive Neurology Clinic from January 2022 to December 2023 were retrospectively recruited, irrespectively of the presence of other cognitive signs. To be included they needed to have undergone measurement of biomarkers of amyloidosis and neurodegeneration (p‐tau, t‐tau, Abeta42‐40 ratio in cerebrospinal fluid or (18F) Flutemetamol‐PET) and extended neuropsychological evaluation. Blind to biomarkers, we classified patients according to the following different clinical criteria: (i) Behavioural or Dysexecutive predominant AD (Ossenkoppele 2015), (ii) Progressive dysexecutive syndrome (Townley 2020), and (iii) behavioural variant of AD (bvAD) (Ossenkoppele 2022). Diagnostic accuracy of each criterion was then compared to biomarkers’ classification for differentiating AD (positive biomarkers) from bvFTD continuum (negative biomarkers). Sensibility and specificity were determined for each criterion and Kappa coefficient used for assessing agreement between different sets of criteria.ResultForty‐six consecutive eligible patients were included. Among them, 45.6% fulfilled criteria for Behavioural predominant AD, 21.7% for Dysexecutive predominant AD, 2.1% for Progressive dysexecutive syndrome, and 52.1% for bvAD. Diagnostic accuracy analyses using biomarkers showed that criteria for Behavioural predominant AD correctly classified 78.2% of patients (sensibility 77.7%, specificity 78.9%), criteria for Dysexecutive predominant AD 67.3% (sensibility 88.8%, specificity 38.8%), criteria for Progressive dysexecutive syndrome 60%, and bvAD criteria 80.4% of patients (sensibility 74%, specificity 89.4%). Higher kappa coefficient (k = 0.85) was found between Behavioural‐predominant AD and bvAD criteria.ConclusionClinical criteria to diagnose patients presenting with mild behavioural or dysexecutive symptoms have poor diagnostic accuracy in absence of biomarkers measurement. Among the criteria available, the definition of bvAD proposed by Ossenkoppele (2022) achieves the more accurate performance in distinguishing AD from bvFTD continuum.
The outcome‐representation learning model of decision‐making capacity in mild cognitive impairment
Authors: Zhang Mang , Zhang Ying , Xie Yuhan , Zheng Yaonan , Wang Luchun , Li Huizi , Yu Xin , Wang Huali 
Published: January 2025

AbstractBackgroundThe decision‐making capacity of persons with mild cognitive impairment (MCI) has not been fully explored. This study aimed to examine the decision‐making capacity in MCI using the outcome‐representation learning model.Method52 persons with MCI and 49 healthy controls were recruited in the study. The Iowa Gambling Task (IGT) was administered to measure decision‐making under ambiguity situations. Five parameters, including the reward learning rate, the punishment learning rate, forgetfulness, win perseverance and deck perseverance, were included in the outcome‐representation learning (ORL) model to capture changes in decision‐making abilities in MCI patients.ResultIndividuals with MCI exhibited reduced learning from losses outcomes and similar learning from wins outcomes compared to healthy controls. Additionally, MCI individuals exhibited less susceptibility to forgetfulness in the IGT compared to controls, suggesting that memory fading of choices made by MCI patients was not improved. Although MCI individuals still favored high‐win frequency decks like controls, their preference appeared to dimmish from the first to second completion of the IGT.ConclusionThe findings suggest that individuals with mild cognitive impairment have difficulty in learning lessons from decision‐making failures in complex contexts. It offers a potential novel computational neurocognitive marker for mild cognitive impairment.
Evidence for a protective effect of hormone replacement therapy on Alzheimer’s disease neuropathological and clinical outcomes across cohorts
Authors: Bruno Jennifer , Shaw Jacob , Henderson Victor W. , Hosseini Hadi 
Published: January 2025

AbstractBackgroundMore than 2/3 of Alzheimer’s Disease (AD) patients are women, which has led to increased interest in the neurophysiological impact of estrogen decline during menopause. While early evidence suggested that hormone replacement therapy (HRT) may be protective against dementia, more recent studies have found inconclusive or even harmful effects.MethodWe tested the association between HRT use (estrogen or estrogen + progestin) and AD‐related neuropathological outcomes measured on autopsy data in females from the National Alzheimer’s Coordinating Center (NACC) (N = 3423). We also sought to test the association between HRT use and molecular imaging and fluid biomarker measures of AD‐related neuropathology measured in‐vivo in females from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset (N = 2422). Finally, we tested the association between HRT use and clinical outcomes, including Clinical Dementia Rating (CDR) and memory performance, in both ADNI (N = 2422) and NACC (N = 20151) datasets.ResultWe found evidence for a protective effect of HRT on the NIA‐AA AD Neuropathologic Change score (ABC score), hippocampal atrophy, and cerebrovascular disease. We also found evidence for a protective effect of HRT on amyloid burden measured via positron emission tomography (PET) and via cerebrospinal fluid as well as on brain metabolism measured via fluorodeoxyglucose PET. Finally, we found evidence for a protective effect of HRT on dementia diagnosis, CDR and memory performance. All results were significant after controlling for age, APOE genotype and educational level.ConclusionWe found evidence for small but significant protective effects of HRT across multiple pathological and clinical measures in two different cohorts. First, the protective effect of HRT on neuropathology measured post‐mortem indicates that HRT use is associated with a lower risk of pathology, relative to no HRT use, on this most definitive and final outcome. Second, the protective effect of HRT extended to amyloid biomarkers measured in vivo indicating that future work can utilize these biomarkers to better understand the protective mechanism by which HRT may act. Finally, the protective effect extended beyond pathology to more subtle cognitive outcomes. Together, these results lend understanding to the effects of HRT (or lack thereof) on the aging brain.
Lower entorhinal cortex thickness is associated with greater temporal discounting in cognitively unimpaired older adults
Authors: Fenton Laura E. , Salminen Lauren , Samek Anya , Weissberger Gali H , Lim Aaron C , Nguyen Annie , Axelrod Jenna , Noriega‐Makarskyy Daisy , Herrera Jennifer , Wei Nathan , Erdman Elizabeth , Han S. Duke 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) neuropathology may impact brain regions involved in decision making. Because of this, changes in decision making (e.g., economic preferences) may be an early behavioral manifestation of preclinical AD. The current study investigated relationships between temporal discounting (the tendency to choose smaller, more immediate rewards over larger, delayed rewards) and brain structures implicated early in preclinical AD.MethodThe sample included 92 cognitively intact older adults (mean age = 68.8±7.43; mean education = 16.62±2.15; 75% female; 79% White). Temporal discounting was characterized using a paradigm in which participants choose between earlier or later payments of varying amounts. In the first section (T1), participants choose between payments today vs. 2 weeks from today. In the second section (T2), choices were between today vs. 4 weeks from today. In the third section (T3), choices were between 2 weeks vs. 4 weeks from today. Temporal discounting rates were calculated for each time point. Due to most participants clustering around a low modal value of temporal discounting, participants were categorized as “low” on temporal discounting if they were at or below the mode and “high” if they were above the mode. Brain structural MRI estimates were acquired on a 7 Tesla scanner and processed using FreeSurfer‐v.7.2.0. The regions of interest (ROIs) included the entorhinal and parahippocampal cortex and hippocampus. Differences in ROIs between the two groups were tested using one‐way ANOVA models adjusted for age, sex, and education.ResultIndividuals who exhibited higher temporal discounting rates at T1 and T2 had significantly lower entorhinal cortex thickness (F = 6.06, p = 0.02 and F = 6.18, p = 0.01 respectively). No significant relationship was observed at T3. Additionally, no significant relationships were observed between temporal discounting and parahippocampal cortex thickness or hippocampal volume.ConclusionResults showed that lower entorhinal cortex thickness is associated with greater temporal discounting in cognitively intact older adults. This supports the idea that changes in economic preferences may be an early behavioral manifestation of preclinical AD. Due to the cross‐sectional nature of the study, it will be important to validate these findings in longitudinal studies.
Sleep quality trajectories and motoric cognitive risk syndrome among Chinese rural older adults: Does gender matter?
Authors: Zhao Dan , Wu Bei , Qi Xiang , Pei Yaolin , Gao Tingting , Li Jie , Wang Yi , Wang Lina , Zhou Chengchao 
Published: January 2025

AbstractBackgroundMotoric cognitive risk syndrome (MCR), a pre‐dementia syndrome, is a risk factor for disability and mortality. However, few studies have examined the associations between sleep quality trajectories and MCR. This study aimed to explore the associations between sleep quality trajectories and MCR, and whether these associations vary by gender among Chinese rural older adults.MethodsWe used three waves of follow‐up data (2019, 2020, and 2022) from the Shandong Rural Elderly Health Cohort (SREHC), including 2,168 participants aged 60 years or above. MCR was defined by the presence of subjective cognitive complaints and slow gait. The Pittsburgh Sleep Quality Index was used to assess sleep quality over the past month. We applied the group‐based trajectory modeling to identify latent groups and estimate sleep quality trajectories. Logistic regression models were performed to examine relationships between sleep quality trajectories and MCR by gender.ResultsThe prevalence of MCR was 13.9% among Chinese rural older adults. Four sleep quality trajectories among males and females were identified, including the normal stable group (male:55.4%; female: 35.4%), the improved quality group (male:23.4%; female: 17.6%), the declined quality group (male:13.0%; female: 25.2%), and the low stable group (male:8.3%; female: 21.8%). After adjusting for covariates, rural older females in the declined quality group (Odds Ratio [OR] = 1.81, 95% Confidence Interval [CI] = 1.19 ‐ 2.77) and the low stable group (OR = 1.65, 95% CI = 1.04 ‐ 2.60) were more likely to have MCR than those in the normal stable group. However, only the declined quality group (OR = 2.00, 95% CI = 1.10 ‐ 3.61) was associated with MCR among male rural older adults.ConclusionOur findings suggest that declined sleep quality was associated with MCR among Chinese rural older males and females. Interventions are needed to focus on addressing sleep quality among rural older adults, which may help prevent MCR.
Shift and night work in the fourth decade is associated with reduced brain volume in late life independent of amyloidogenic pathways: an Insight 46 study
Authors: King‐Robson Josh , Nicholas Jennifer M , James Sarah‐Naomi , Sudre Carole H , Lu Kirsty , Barnes Jo , Brown Thomas M. , Coath William , Cash David M ,   Insight 46 Study Team, Warren Jason D , Richards Marcus , Schott Jonathan M 
Published: January 2025

AbstractBackgroundSleep and circadian disruption are associated with increased dementia risk, yet the mechanism remains poorly understood. We examined the relationship between night/shift working in the fourth decade and late‐life brain health. We explored whether significant relationships were mediated by life course factors including cardiovascular risk.MethodsNight/shift working (yes/no) was recorded prospectively at age 31. Smoking, alcohol intake, body mass index, exercise, blood pressure, and Framingham risk scores (FRS) were determined at 3‐6 timepoints across the life course (age 20, 36, 43, 53, 60‐64, 68‐70). Whole‐brain and hippocampal volumes, white matter hyperintensity volume (WMHV), and β‐amyloid PET SUVr were derived from T1, fluid‐attenuated inversion recovery, and 18F‐Florbetapir PET, respectively, at age ∼73.Associations between night/shift working, life course cardiovascular risk factors, and imaging metrics were examined with linear regression. Causal mediation analysis (gformula approach in R), examined whether significant relationships between night/shift working and imaging metrics were mediated by life course cardiovascular risk factors. Analyses were adjusted for gender, adult socioeconomic status, educational attainment, age at imaging, and intracranial volume for volumetric measures.Results432 participants had available data, of whom 74 (17.1%) were night/shift workers. Night/shift workers had lower whole brain volume (‐26.2 ml, 95% CI ‐39.3, ‐13.0, P < 0.001, Figure 1), without evidence of a significant difference in hippocampal volume, WMHV, or amyloid‐β SUVr. Night/shift workers had 0.6% higher FRS (95% CI; 0.23%, 0.91%; P = 0.001) and higher alcohol consumption age 36 (5.7 g/day, 95% CI, 0.3, 11.2, P = 0.04); higher alcohol consumption age 60‐64 (10.7 g/day, 95% CI, 4.5, 16.9; P < 0.001); and smoked an additional 5.7 pack‐years by age 60‐64 (95% CI 1.9, 9.4; P = 0.003, Figure 2). 35% of the brain volume reduction in shift workers was mediated by cardiovascular risk factors (Figure 3).ConclusionShift working in the early 30s is associated with lower brain volume in late‐life independent of amyloidogenic pathways. While partially mediated by increased cardiovascular risk factors in night/shift workers, the majority of the effect is unexplained and may be a direct effect of night/shift working on brain health.
Investigating test‐specific practice effects on self‐administered mobile‐based cognitive tasks in two diverse community‐based cohorts
Authors: Christianson Kieffer , De Anda‐Duran Ileana , Karjadi Cody , Hathaway Lindsay , Monteverde Jose R , Devine Sherral A. , Ang Ting Fang Alvin , Hwang Phillip H , Bazzano Lydia , Kolachalama Vijaya B. , Lin Honghuang , Au Rhoda , Sunderaraman Preeti 
Published: January 2025

AbstractBackgroundRepeated self‐administered mobile‐based cognitive assessments are increasingly being utilized to identify preclinical cognitive decline. Repetition of cognitive tests during a short time interval often leads to improved performance (i.e., practice effects) due to familiarity with test structure. Therefore, test‐specific practice effects may delay the detection of subtle decline. Alternatively, the lack of practice effect may indicate a decline in cognitive function. This study investigated whether practice effects were present on three digital tests repeated over a 3‐month interval in two cognitively unimpaired cohorts.Method549 cognitively intact participants (average age 63.5 years, 40.6% male, 89.6% white) enrolled in the Framingham Heart Study and 26 cognitively unimpaired participants (average age 55 years, 15.4% male, 80.8% white) from the Bogalusa Heart Study completed three self‐administered subtests from Digital Automated Neurobehavioral Assessment (DANA) on their own mobile device at baseline (T1) and three months later (T2). Cognitive scores were calculated using Cognitive Efficiency (CE), a derived measure of speed and accuracy, for Code Substitution (CS), Simple Reaction Time (SRT), and Go/No‐Go (GNG). CS assesses visual scanning and attention, learning, and immediate recall; SRT measures pure reaction time; and GNG assesses sustained attention and impulsivity. For each cohort, separate paired sample t‐tests examined mean differences in CE between timepoints for all three tests.ResultOn all three tests, similar trends in test performance were found in both cohorts. FHS participant’s CE scores significantly improved at T2 compared to T1 on CS and GNG, but not on SRT (Table 2). Similar trends were observed among BHS participants, with more relative improvements on CS and GNG compared to SRT.ConclusionThis study found similar trends in test‐specific practice effects on mobile‐based cognitive tests in two different cohorts. CS and GNG are inherently more complex than SRT, which may explain why test familiarity improved performance three months after baseline. This is congruent with traditional paper‐and‐pencil neuropsychological tests, wherein tests with complex stimuli show more practice effects relative to simple tasks. Additional research is needed to determine which tests are more sensitive to detecting earliest indicators of cognitive decline, and whether the presence/absence of practice effects itself are clinically meaningful.
Sleep apnea risk, subjective cognitive decline, and cognitive performance: Findings from the Boston Latino Aging Study (BLAST)
Authors: McDowell Celina F. Pluim , Giudicessi Averi , Martinez Jairo E. , Badillo‐Cabrera Alex L , Félix Nikole A Bonillas , Martinez Lusiana , Munera Diana , Vila‐Castelar Clara , Schwab Nadine A , Gomez Liliana A Ramirez , Catalan Marta Gonzalez , Duffy Jeanne F. , Cronin‐Golomb Alice , Quiroz Yakeel T. 
Published: January 2025

AbstractBackgroundSleep apnea is associated with risk of objectively‐measured cognitive decline and dementia, as well as with subjective cognitive decline (SCD), itself a risk factor for cognitive decline and dementia. This relationship is understudied in ethnoracially diverse groups, however, including Latinos. This study examined associations among self‐reported sleep apnea risk, SCD, and cognitive performance in community‐dwelling older Latino adults.MethodFifty‐six participants (39 men, 17 women) from the Boston Latino Aging Study (BLAST) were included (Mage = 66.5 years [SD = 8.6]; Meducation 10.5 years [SD = 5.2]. Participants were administered the Preclinical Alzheimer’s Cognitive Composite‐5 (PACC5) (z‐scores), the Berlin Questionnaire to assess sleep apnea risk, in which positive scores in at least 2 categories (snoring and cessation of breathing; excessive daytime sleepiness; BMI and hypertension) indicates high risk, and the Cognitive Function Instrument (CFI) to assess SCD, in which higher scores indicate greater SCD. The Mini‐Mental State Examination (MMSE) measured global cognition. Pearson or point‐biserial correlations assessed associations among demographic factors (e.g., age, education), sleep apnea risk, SCD, and cognitive performance. T‐tests examined demographic and cognitive differences between those at high/low risk of sleep apnea.ResultOn average, participants had intact global cognition (MMSE; M = 26.6 [3.3], range 16‐30) and mild SCD (CFI; M = 4.3 [3.8]). Thirty participants were classified as high risk for sleep apnea. Older age (r = ‐.35, p = .037) and fewer years of education (r = .68, p<.001) correlated with worse PACC5 performance. There was a trend for an association between high sleep apnea risk and worse PACC5 performance (r = ‐.32, p = .058). No other associations among demographics, sleep apnea risk, and cognition were significant (p’s>.16). Relative to those at low risk, those at high risk for sleep apnea had greater SCD (p = .018) and worse global cognitive performance (p = .019).ConclusionThese findings suggest that self‐reported sleep apnea risk may signal risk for cognitive decline in older Latinos. Screening for sleep apnea using a questionnaire may help identify those experiencing early cognitive decline or at risk of future decline. More work with larger sample sizes is needed to confirm these associations; BLAST data collection is ongoing.
Measuring Visuospatial Ability in Low‐Literacy Older Adults: A Comparison of the Constructional Praxis and Stick Design Tests in Rural South Africa
Authors: Bassil Darina T. , Farrell Meagan T. , Guo Muqi , Gao Sarah , Mahlalehla Nomsa , Brickman Adam M. , Manly Jennifer J. , Berkman Lisa F. 
Published: January 2025

AbstractBackgroundDementia criteria require not only memory impairment, but additional impairment in at least one other cognitive domain, like visuospatial functioning. Cognitive measures assessing visuospatial function often involve drawing shapes. While these measures have proven reliable and valid in developed countries, their use in Low and Middle‐income Countries (LMICs) is challenging due to cultural differences and low literacy. Cultural and educational bias in visuospatial tests prevents comprehensive assessment of neuropsychological function, thus limiting dementia assessment in LMICs. Here, we compare the Stick Design Test (SDT) to Constructional Praxis (CP) for assessing visuospatial functioning among older South Africans adults.MethodWe used data from Cognition and Dementia in the Health and Aging in Africa: A Longitudinal Study in South Africa (HAALSI‐HCAP), a population‐based nested cohort study in rural Agincourt, South Africa. In 2022, 675 participants, aged ≥ 50, were administered the immediate and delayed recall trials of the SDT and CP, as part of HAALSI‐HCAP cognitive battery. CP, completed on a tablet, involved copying four geometric shapes, while SDT required participants to reconstruct four configurations using matchsticks. Scoring for both CP (0‐11) and SDT (0‐12) was subsequently completed by trained researchers. We assessed acceptability and performance of both measures across participant demographics and investigated their correlation with performance on other visuospatial measures to ascertain criterion validity.ResultParticipants were mostly women (63%), without education (58%) with mean age of 72.5±11. Refusals and missingness were more common for CP (40%) than SDT (13%). SDT had a more normal distribution compared to CP, overall and for individual figures. Worse performance was associated with higher age and lack of formal education for both measures. However, SDT demonstrated less extreme z‐standardized scores, particularly among those without education and over 70 years old. Participants were more likely to recall SDT configurations than CP figures after a delay. SDT showed weak but significant correlations (p<0.001) with CP(r = 0.14), Raven’s Matrices(r = 0.27), and Symbol Cancellation (r = 0.38).ConclusionSDT outperformed CP in acceptability and demonstrated lower sensitivity to education. Convergent validity findings suggest that SDT may be a robust and culturally adaptable measure for assessing visuospatial functioning in older populations, especially in low‐resource settings.