bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying change on the CERAD Word List with standardized regression‐based scores
Authors: Duff Kevin , Hanna Elise J , Mattek Nora , DeCapo Madison , Hantke Nathan , Pierce Aimee , Kaye Jeffrey A
Published: December 2023

Background

List learning and memory tests are frequently used to evaluate older adults for Mild Cognitive Impairment and Alzheimer’s disease. One such test, the Word List subtest of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), has been widely‐used in clinical trials track such disorders. However, data is lacking on the amount of change that is needed to accurately identify decline.

Method

Participants included 897 older adults (age in years: M = 81.1, SD = 8.1, range 55‐100; 67% women; education in years: M = 14.8, SD = 2.8, range = 7‐24) who were cognitively intact at two annual visits in a longitudinal observational study from the Uniform Data Set of the National Alzheimer’s Coordinating Center. Each participant completed the Word List subtest at two visits, which were approximately 1 year apart (interval in years: M = 1.3, SD = 1.0). Multiple linear regression predicted Time 2 scores from Time 1 scores and simple demographic variables (age, sex, education). The predicted Time 2 scores were compared to observed Time 2 scores to preliminarily validate this change data.

Result

For three primary scores from the Word List subtest (Acquisition Total Correct, Delay Recall Total Correct, Recognition Total Correct), the Time 2 scores were significantly predicted from the other variables, with R2s ranging from 0.16 – 0.41 (p‐values<0.001). When these predicted Time 2 scores were compared to observed Time 2 scores, there were no significant differences (p‐values≧0.19), indicating preliminary support for these prediction scores.

Conclusion

The current prediction equations appear to allow clinicians and researchers to accurately track change on the Word List subtest of the CERAD by comparing their patients/participants to the current sample of robustly intact older adults. Consistent with past work in this area, Time 1 cognitive scores were the best predictors of Time 2 cognitive scores, although demographic variables added to that prediction. Future work should consider if additional variables can improve the prediction equations. Future work should also validate these equations in independent samples to examine their clinical utility.
Long term high‐fat feeding induces cognitive impairment, alterations in microglial morphology, and spatial transcriptomic changes
Authors: Elzinga Sarah E , Noureldein Mohamed , Guo Kai , Jang Dae Gyu , Hayes John M , Henn Rosemary E , Webber‐Davis Ian , Mendelson Faye E , Parent Rachel , Rigan Diana M , Glass Emily , Turfah Ali , Zhao Lili , Murphy Geoffrey G , Hur Junguk , Feldman Eva L
Published: December 2023

Background

Obesity and metabolic dysfunction (Metabolic Syndrome, prediabetes, and diabetes) increase the risk of later life cognitive impairment, including dementias such as Alzheimer’s Disease1‐3. One common etiology that might underly this increased risk is immune system dysregulation and inflammation4, 5. Specifically, microglial dependent mechanisms are thought to play an important role in pathology6‐8. However, the precise immune and inflammatory mechanisms promoting cognitive decline secondary to obesity and metabolic dysfunction are unclear.

Method

BL6 male mice were fed 60% HFD (high fat diet) or 10% SD (standard diet) for 1 year. Body weight and glucose tolerance were assessed longitudinally. Cognition was repeatedly evaluated using Morris water maze, social recognition, and puzzle box. At study termination, mice were given either an intraperitoneal injection of lipopolysaccharide as an immune challenge or saline as a control. Activation of hippocampal microglia was assessed via immunohistochemistry (IHC) and analysis of microglial morphology. Changes in brain gene expression were measured via spatial transcriptomics using the 10X Visium platform.

Result

HFD feeding caused increased weight, impaired glucose tolerance, and cognitive deficits which persisted throughout the study period. Body weight in particular was predictive of cognitive changes, especially for later time points. In response to immune challenge, hippocampal microglia in SD mice had a normal morphological response indicative of activation. However, microglia of HFD mice had no change in their morphology in response to lipopolysaccharide injection. Additionally, changes in morphology significantly correlated with cognition and indicated that a higher percentage of activated hippocampal microglia is associated with a worse cognitive phenotype. Spatial transcriptomics analysis showed changes in gene expression in multiple brain regions of HFD mice, including the hippocampus, many of which were related to neurodegenerative and inflammatory pathways.

Conclusion

These data support that HFD feeding causes an early and persistent cognitive impairment, which is associated with obesity. Our data also confirm a role for microglia in HFD‐induced cognitive impairment. Indeed, microglial and transcriptomic data strongly indicate a role for inflammation and inflammatory pathways in HFD‐induced cognitive impairment.
Social network as a catalyzer of adherence to risk factor control in subjects with a subjective memory complaint
Authors: Cristalli Carolina Agata Ardohain , Seminara Emiliana , Hernández Micaela A , Elgani Sofía Alejandra , Calandri Ismael Luis , Allegri Ricardo Francisco
Published: December 2023

Background

Subjective memory complaint (SMC) is defined as the perception of memory deficits despite a normal cognitive assessment, it is related to long‐term cognitive decline risk. The guidelines recommend medical advice about risk factor control, a healthy diet, and regular exercise for lower risk. However, there is no evidence that would guarantee good adherence. Social networks are conduits of support, information, and health behavior flows, they may have an impact on SMC adherence to the suggested changes. Our aim is a) to assess long‐term adherence of SMC to lifestyle changes b) to evaluate social networks as a predictor of adherence.

Methods

Prospective cohort study recruiting SCM participants with a normal UDS3 neuropsychological battery. Participants were evaluated on individual risk based on CAIDE score and received guideline‐based recommendations about lifestyle changes. Subjects were re‐evaluated 6 months after recommendations to assess their adherence to a healthy diet (MIND score), physical activity (IPAQ), risk factor control, and their social network (Figure 1). We fitted a generalized linear model to predict IPAQscore and MINDscore with social network features.

Results

We recruited 200 participants (age 68.1 ± 6.5; 62% female; 57% first‐degree family history of dementia, and 15.91±2.28 years of education). Participants presented a 7.55±2.04 CAIDE score (Table 1): 37% high blood pressure, 51% obesity, dyslipidemia 43%, Social isolation 25%, 51% sedentarism, 9% smoking, and 22% heavy drinking. Six months after medical advice, 15% stopped drinking, 5.1% quit smoking, 37% started physical activity, and 66% a healthy diet. Regarding social networks, the median size of the network was 8 IQR[5‐12], 50% were kin, gender diversity: IQV = 0.77; 50% IQR[20%‐60%] sedentary, 20% IQR[0%‐44%] unhealthy diet. The percentage of sedentary social network members was a predictor of the intensity of the weekly physical activity of participants (in METS/minutes/week)(β ‐2.82 95%CI[‐4.7,‐9.27] p = 0.005) (Table 2).

Conclusion

Participants showed good adherence to the proposed intervention. Social networks have an impact on adherence and it is a potential target to prevent dementia.
Preliminary Effects of Aerobic Exercise, Training Dose, and Cardiorespiratory Fitness on Resting Plasma Neurotrophic Factors in Alzheimer’s Dementia in the FIT‐AD Trial
Authors: Salisbury Dereck , Li Danni , Todd Michael , Ng Ted K.S. , Yu Fang
Published: December 2023

Background

Vascular factors are increasingly recognized for their roles in the pathogenesis and progression of Alzheimer’s dementia (AD). Cardiorespiratory fitness (CRF), a physiologic indicator of cardiovascular health, and plasma neurotrophic factors, endogenous soluble proteins in the periphery, have been linked to cognition, brain structure and function, and AD and are modifiable by aerobic exercise (AEx), but their interplay remains poorly understood. The objective of this pilot study was to estimate the effect sizes of 6‐month AEx on resting plasma neurotrophic factors and the relationships of CRF and exercise dose with change in resting plasma neurotrophic factors in AD.

Method

This study was a pilot blood ancillary study of the FIT‐AD Trial that randomized participants to 6‐month AEx or stretching control on a 2:1 allocation ratio. The blood study enrolled 26 participants (AEx Group [n = 18] and stretching control [n = 8]). Resting plasma brain‐derived neurotrophic factor (BDNF), irisin, fibroblast growth factor‐21 (FGF‐21], and insulin‐like growth factor‐1 (IGF‐1), and CRF (peak oxygen consumption) were assessed at baseline, 3 and 6 months. Exercise dose was calculated by the heart rate physical activity score (HRPAS) method.

Result

The sample was 77.6±6.99 years of age and had 15.4±3.00 years of education on average. Sixty‐five percent of the participants were male and 96.2% carried at least one copy of APOE e4. Most 6‐month between‐group effect sizes were small except for irisin (d = ‐0.44), indicating that the irisin levels decreased in the AEx group relative to stretching control. The association between exercise dose and changes in CRF with changes in neurotrophic biomarker were weak (r2 ≤ 0.025).

Conclusion

The effects of exercise on BDNF, irisin, IGF‐1, and FGF‐21 may be heterogeneous in AD. Weak associations of exercise dose and CRF changes with changes in resting neurotrophic biomarkers were seen. There were weak associations of exercise dose and CRF changes with changes in resting neurotrophic biomarkers. Our findings need to be validated in future, adequately powered exercise studies in AD.
Experience in mixed vascular dementia in the genetic bank of the School of Medicine, University of Buenos Aires, Argentina
Authors: Brusco Luis Ignacio , Muchnik Carolina , Olivar Natividad
Published: December 2023

Background

Alzheimer’s disease (AD) is the most common form of dementia. The sporadic forms represent 95% whereas 5% assumes to the familiar forms. Among the genetic factors of Alzheimer’s disease is genotype for APOE variant e4 which is associated to a major risk of suffering the illness. There is a mixed vascular component, that is to say vascular dementia and Alzheimer’s disease which might be related to the same gene APOE‐e4 in homozygous or heterozygous. To analyze the influence of APOE genotype and the mixed vascular component in the development of AD and the allelic and genotypic distribution of APOE in our population is our aim.

Method

In the genetic bank of dementias of the School of Medicine (of the) University of Buenos Aires we have selectively studied those patients with vascular commitment and Alzheimer’s disease. It was noted the association of risk between this gene and Alzheimer’s disease in our population, as well as is possible it’s association with the mixed component of the patients with dementia.

Population under study: 1) AD Patients
: The clinical diagnosis was made according to the NICDS‐ADRDA criteria. (n = 49, 20 men and 29 women).
2) >60 years Controls
: subjects with no history of neurological diseases (n = 31.8 men and 23 women).
3) Population Controls
: (n = 70, 24 men and 46 women).

Result

A significant association between APOE‐ ε4 allele, mixed vascular component and AD was found. Even higher than the ApoE‐4 component of AD. About the influence of the genotype in the AD of delayed beginning aour results was: controles vs. AD, OR: 3,70 (1,43 ‐ 1,57), p<0,01 / controles>60 years vs. AD, OR: 4,32 (1,47 ‐ 12,43), p<0,02. And we found the relation between Apo ‐ e Genotype in Mixed Dementia and AD was AD vs controles, OR = 4,1, RR = 1,6, p<0,0001 / DM vs controles, OR = 10,3, RR = 4,1, p<0,0005

Conclusion

Our results suggests that it may correspond to an increased risk of outbreak of the physiopathology of AD in patients with vascular injury and / or cerebral hypoxia. The APOE‐4 would be a risk factor for vascular injury remaining unprotected brain, resulting in mixed demetia.
SARS‐CoV‐2 Associated Neurocognitive Disorder (SAND): Molecular validation of a pathogenetic hypothesis
Authors: Vavougios George D. , Mysiris Dimitrios , Foka Pelagia , Mavridis Theodore , Stavrou Vasileios , Papaggeli Olga , Zarogiannis Sotirios G , Xiromerisiou Georgia , Artemiadis Artemios , Gourgoulianis Konstantinos , Snyder Heather M , de Erausquin Gabriel A. , Hadjigeorgiou Georgios M. ,   COVALENT
Published: December 2023

Background

Type I interferon signalling dysregulation is a hallmark of SARS‐CoV‐2 infection and among significantly perturbed pathways in Alzheimer’s disease. In a previous study, we predicted the involvement of this pathway in the development of SARS‐CoV‐2 Associated Neurocognitive Disorder (SAND) via a crosstalk between peripheral immunity and the CNS. The purpose of this study is to determine whether current data support provide external validation to our pathogenetic hypothesis.

Method

Data for our validation analyses were leveraged from studies of frontal cortex (FC) transcriptomes donated by Alzheimer’s disease and COVID‐19 patients vs. controls, respectively. An additional dataset of nasal epithelial cells from COVID‐19 patients was also used as a putative crosstalk site. Enrichment analyses were employed to provide an unbiased estimate of the enrichment of Type I interferon responses. Furthermore, we performed a literature search in order to identify studies on the effects of COVID‐19 on two different settings: (a) to determine the effects of peripheral exosome cargo on CNS tissue (b) to determine the cargo of neuronal‐derived exosomes. For enrichment analyses, a false discover rate (FDR) <0.05 was considered statistically significant.

Result

The type I interferon pathway (IFN‐I; GO:0060337) was significantly enriched in both Alzheimer’s disease and COVID‐19 FC transcriptomes, as well as nasal epithelia of COVID‐19 patients. Common genes in both IFN‐I FC signatures included PSMB8, IP6K2, IFI35, EGR1, ISG20, MYD88, IFITM1, SP100, GBP2, IFITM3, OASL, IRF1, IRF2, MX2, IFNA2, IRF9, IFIT3, STAT2, HLA‐C, SAMHD1, IFI27, IFITM2, IRF7, BST2. At least one study reports on miR‐148a and miR‐590 as exosomal cargo of infected non‐neuronal cells capable of affecting IFN‐I responses and inducing microglial activation, supporting the role of exosomes as facilitators of IFN‐I crosstalk between the periphery and the CNS. Correspondingly, at least one study reports on proteopathic seeds as cargo of neuron‐derived exosomes.

Conclusion

Independent studies and data support continue to corroborate our hypothesis that type I interferon pathway dysregulation as a result of peripheral – CNS immune crosstalk may mediate neuroinflammation and Alzheimer’s disease‐like pathology as observed in SAND.
Multi‐modal Imaging‐based peudotime analysis for AD progression
Authors: He Bing , Risacher Shannon L. , Saykin Andrew J. , Yan Jingwen
Published: December 2023

Background

Alzheimer’s disease (AD) progresses along a continuum and begins many years before symptom onset. AD takes a long progression time, making it hard to study the entire spectrum of AD development. Pseudotime analysis widely used in cell lineage analysis have been applied to AD gene expression data to understand the molecular changes along progression. In this work, we performed a neuroimaging‐based pseudotime analysis to explore the progression patterns of different imaging modalities.

Method

Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (https://adni.loni.usc.edu/). Data from three imaging modalities were collected including MRI (N = 1684), Amyloid (N = 1041), and Tau (N = 540) (Table.1). Out of those, 223 subjects have all three modalities. We tested four different pseudotime analysis tools: PHATE, MONOCLE3, Slingshot, and Destiny. MRI, Amyloid, Tau, and the combined multi‐modality data were used to estimate the pseudotime respectively. Only PHATE returned non‐reversed pseudotime and clear disease trajectories

Result

Amyloid derived pseudotime best captures the continuum of disease progression and differentiate diagnosis groups the best (Fig.1(b,f)). It also showed better correlation with clinical cognition scores than the composite amyloid measure (Fig.2(b,d)). Multi‐modality derived pseudotime reveals turning point of Amyloid and Tau. We found that the accumulation of Amyloid starts to accelerate when the composite SUVR reaches ∼1.2, which agrees well with existing findings (Fig.2(g,h)). Such turning point does not exist for amyloid derived pseudotime. It also reveals temporal order of brain changes within and across modalities (Fig.2(e,f)), where we observed overall amyloid changes starts early (i.e., small pseudotime) and accelerates earlier than overall brain atrophy and Tau deposition. With a closer look into Tau regions, we found Tau deposition in BRAAK 1 regions accumulates in a faster rate than those inBRAAK34 and BRAAK56 regions.

Conclusion

Pseudotime analysis has a great potential for us to better understand the progression of Alzheimer’s disease. New approaches to fully leverage the longitudinal imaging data could provide a refined view of imaging changes and their co‐occurance pattern along AD progression. Longitudinal data in pseudotime analysis could also help capture the subtle changes in very early stage and therefore would likely provide some valuable insights to improve early diagnosis.
A supervised machine learning approach to predicting mild cognitive impairment among diverse Hispanics/Latinos: The SOL‐INCA Study
Authors: Kuwayama Sayaka , González Kevin A , Márquez Freddie , Gallo Linda C , González Hector M , Tarraf Wassim
Published: December 2023

Background

Existing literature highlights the need for better risk assessment of mild cognitive impairment (MCI) to mitigate the onset and burden of Alzheimer’s Disease and Related Dementia (ADRD) through earlier interventions. Hispanics/Latinos are the largest US ethnic/racial minority, at higher risk for developing ADRD compared to Non‐Hispanic Whites, but underrepresented in dementia‐related research. This study develops prediction models for targetable protective and risk factors of MCI in diverse, middle‐aged Hispanics/Latinos in the US.

Method

We use data (n = 4246, average baseline age = 56‐years) from the Hispanic Community Health Study/ Study of Latinos (HCHS/SOL; 2008‐2011), a multisite prospective cohort study of diverse Hispanic/ Latinos, and its ancillary study, the SOL‐Investigation of Neurocognitive Aging (SOL‐INCA). Our outcome is prevalent MCI at SOL‐INCA visit (average 7‐years after the baseline) operationalized based on National Institutes of Aging‐Alzheimer’s Association criteria. Using nearly 40 baseline indicators representing (1) sociodemographic characteristics, (2) childhood factors, (3) acculturation factors, (4) biological and (5) behavioral markers, and (6) mental and (7) functional health, we compared a supervised machine learning (Random Forest; RF) and a standard statistical technique (logistic regression; LR) in identifying predictors. Additionally, to evaluate RF as a feature selection tool, we estimated Area Under the Curve (AUC) from LR using all factors and a subset of factors identified as important by RF.

Result

LR identified socioeconomic conditions and mental and physical health scores as among the leading factors predicting MCI. RF identified a larger subset of predictors and differed from LR in ranking the relative importance of common predictors. Removal of factors identified as insignificant in predicting MCI by RF (n = 17) slightly improved classification performance in LR (AUCall factors = 0.692, AUCsubset by RF = 0.697).

Conclusion

Supervised machine learning (ML) identified different predictors for MCI compared to standard methods and was compelling as a feature selection method. This suggests potential value of ML to focus on significant predictors for MCI prediction. Substantively, our findings emphasize the importance of accounting for life‐course risk and protective factors for predicting cognitive health. Further investigations are needed to test additional ML modalities and better understand how complex interactions of life‐course multi‐domain factors can be addressed through interventions.
Angiotensin‐converting enzyme‐1, ACE‐1, and ACE‐2 are dysregulated in Alzheimer’s disease and related to ACE1 genotype
Authors: Guzel Ozge , Tayler Hannah Mary , Miners James Scott , Kehoe Patrick Gavin
Published: December 2023

Background

The renin‐angiotensin system (RAS) is dysregulated in Alzheimer’s disease (AD): angiotensin‐converting enzyme (ACE‐1) activity, a rate‐limiting enzyme in the disease‐associated classical RAS (cRAS) pathway, is elevated, whereas ACE‐2 activity, a central mediator of the counter‐regulatory protective pathway (rRAS) (that generates Ang‐(1‐7) from Ang‐II) is defective. Previous meta‐analyses, more recently confirmed in GWAS studies, indicate that ACE1 variants, including an insertion (I)/deletion (D) (indel) polymorphism at intron 16, are risk variants in AD. In this study, we have determined if ACE‐1 and ACE‐2 are dysregulated in AD in relation to ACE1 variant (rs4343) (a proxy marker for the more commonly studied indel polymorphism).

Method

We studied brain tissue from the frontal and parietal cortex from 147 dementia cases (AD (n = 94) and vascular dementia n = 20 and mixed AD/VaD (n = 33)) and 104 age‐matched controls from the South West Dementia Brain Bank, University of Bristol. ACE‐1 and ACE‐2 protein levels were measured by ELISA, and enzyme activities were measured using fluorogenic peptide substrate assays. ACE1 (rs4343) polymorphism was genotyped by PCR.

Result

ACE‐1 protein level was increased (p<0.0001) and ACE‐2 protein level reduced (p = 0.0103) in AD cases compared to controls in the parietal cortex. In contrast, no significant changes in protein level were observed in the frontal cortex. ACE‐1 enzyme activity was elevated (p<0.0001) as was ACE‐2 enzyme activity in both frontal and parietal cortices (p<0.0001 and p = 0.001 respectively) in AD. Individuals with I/I compared with D/D and I/D genotypes in AD had unchanged ACE‐1 level (p = 0.079), lower ACE‐1 enzyme activity (p = 0.029), higher ACE‐2 level (p = 0.011) and unaltered ACE‐2 enzyme activity (p = 0.085) in the frontal cortex.

Conclusion

These data confirm our previous findings showing that RAS is dysregulated in AD. Interestingly, we report regional differences in RAS signalling in AD and a reciprocal relationship between ACE‐2 protein level (reduced) and enzyme activity (increased) in AD that warrants further investigation. RAS appears to be most dysregulated in individuals with an I/I genotype in AD.
Event‐related potential signatures of episodic memory decline predicting progression to Alzheimer’s disease in asymptomatic at‐risk subjects: a longitudinal study.
Authors: Pereira Filipa Raposo , Chaumon Maximilien , Dubois Bruno , La Corte Valentina , George Nathalie
Published: December 2023

Background

The challenge in Alzheimer’s disease (AD) research ‐the world most prevalent dementia‐remains on finding preclinical markers that can predict progression to the disease. In this respect electrophysiological (EEG) measures seem promising, based on their sensitivity to the appearance of subtle episodic memory (EM) alterations, which become an AD risk‐factor when in the presence of B‐amyloid burden (AB+; AD‐biomarker) (Paitel et al., 2021; Olichney et al., 2011). We aimed to identify event‐related potential (ERP) signatures of AD‐linked EM alterations in elder cognitively normal subjects at‐risk for AD.

Methods

EEG data was collected longitudinally with an EGI 256‐channels cap, over 6 yearly sessions, in 15 controls (AB‐), 15 non‐converters (AB+), and 15 converters to prodromal‐AD (AB+; who converted during follow‐up but were only considered before diagnosis) from the INSIGHTpre‐AD cohort. We analysed the typical ERP response to a classic task of verbal memory recognition of old or new words (i.e. P3 and FN400 [0.25‐0.34 and 0.51‐0.57ms], P600 [0.62‐0.77ms], and monitoring [0.87‐1.04ms]). The new words were related to the old words (previously encoded) either in their number of repetitions (NR) or in their semantic content but presented once (NU). Source‐localization analysis of these data is currently underway.

Results

During follow‐up, the converters showed increased reaction time and decreased accuracy in word recognition when compared with the other groups. The converters significantly showed greater mean amplitude in the fronto‐parietal left and parieto‐occipital central regions typically linked to EM recollection, in the 0.25‐0.34 ms time‐window when compared with the controls, and in the 0.51‐0.57ms time‐window when compared with the non‐converters. Through our period of interest, old words activated mostly central‐posterior left regions (semantic networks/familiarity), NR words activated the frontal right region (i.e. novelty detection), and NU words frontal‐temporal right regions (semantic interference detection).

Conclusion

Our findings show amplitude differences associated with AD‐linked EM alterations years before individuals are diagnosed, representing potential ERP signatures of progression to AD in at‐risk individuals, while they remain cognitively normal. Anticipation of diagnosis contributes to the development of more effective tailor‐made treatments that potentially ease quality of life of patients and caregivers.
Feasibility of a Synchronous, Remoted‐Delivered, Aerobic Exercise Training Program in Rural‐Dwelling Adults with Subjective Cognitive Decline ‐ The MN RIDE Pilot
Authors: Salisbury Dereck , Soderlund Patricia R , Fergen Joshua , Cruikshank Kirsten R , Shaughnessy Keith , Anderson Timothy , Warry Wayne , Jacklin Kristen
Published: December 2023

Background

Subjective cognitive decline (SCD), the subjective experience of worsening memory or cognition, is one of the earliest noticeable symptoms of Alzheimer’s disease and related dementias (ADRD), and offers a therapeutic window where interventions have strong potential to prevent or delay the progression to the ADRD. Out of all the modifiable risk factors for ADRD, physical inactivity is the strongest; therefore, it is no surprise that exercise is linked to a 30‐40% risk reduction for ADRD, with moderate intensity being the most beneficial. Rural communities have greater barriers in participating in exercise due to lack of social support, travel/weather problems, and lack of facilities/equipment. The purpose of this pilot study was to implement and evaluate the feasibility of a synchronous, remoted‐delivered, aerobic exercise (AEx) training program in persons with SCD living in rural areas.

Method

The MN RIDE Pilot Study employed a single group, pre‐posttest design. Participants were shipped all needed equipment to complete the intervention (cycle, heart rate monitors, etc.). All AEx sessions were supervised remotely via smart devices and Zoom® by an exercise physiologist. AEx was prescribed as progressive, moderate‐intensity cycling for 20‐50 minutes, 3 times/week for 3 months (36 sessions). Intensity was evaluated using the Borg Rating of Perceived Exertion (RPE) 6‐20 scale and heart rate max (HRmax) methods. Moderate intensity was defined as RPE 13 and HRmax 64‐76%. Feasibility was assessed by session attendance, intensity adherence, and presence of adverse events.

Result

The average age of the study sample (n = 9) was 57.44±7.16 years old (average age of SCD onset 53.44 [7.47] years old) with 14.00±5.57 years of education and 77.8% female. Out of the possible 324 sessions scheduled, 276 were attended (86% session adherence). Average intensity metrics achieved over the AEx sessions were 13.2 (0.5) and 72.0 (7.9) for RPE and HRmax respectively. No adverse events were reported.

Conclusion

Our study provides preliminary evidence of the feasibility of AEx telerehabilitation program designed to reduced ADRD risk in persons with SCD living in underserved rural communities. AEx telerehabilitation in rural communities should be further explored given AEx’s potential to reduce ADRD risk.
Prevalence of Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) in the United States Medicare population
Authors: Zhang Haixin , Zhang Quanwu , Monfared Amir Abbas Tahami
Published: December 2023

Background

Alzheimer’s disease (AD) is a chronic, neurodegenerative health condition. Mild cognitive impairment (MCI) is characterized by cognitive decline, without dementia. We aimed to estimate the prevalence of AD and MCI among Medicare beneficiaries.

Method

Patients were identified from the US Center for Medicare and Medicaid Services (CMS) database using International Classification of Diseases (ICD) codes for AD (331.0, G30.9, G30.8, or G30.1,) and MCI (331.83 or G31.84). Both AD and MCI were identified using the search rule of 2 ICD codes ≥30 days apart ≤365 days from both Medicare fee‐for‐service (FFS: 2008‐2018) and Medicare Advantage (MA: 2015‐2018). US regions were derived using zip codes and categorized by National Center for Chronic Disease Prevention/Health Promotion regions. Yearly prevalence was defined as the number of cases of AD or MCI in each year divided by the Medicare population in the year. Confidence intervals were not reported due to small intervals.

Result

The prevalence of AD and MCI was 1.9% and 0.1% (2008), 2.5 and 0.2% (2009), 2.7 and 0.2% (2010), 2.7 and 0.3% (2011), 2.8 and 0.4% (2012), 2.8 and 0.5% (2013), 2.8 and 0.6% (2014), 2.8 and 0.7% (2015), 2.3 and 0.7% (2016), 2.4 and 0.9% (2017), and 2.3 and 1% (2018), respectively. About 1.2 million AD patients and 490,000 MCI patients were identified in 2018. The prevalence of AD vs MCI among demographic subgroups in 2018 was 1.81% vs 0.85% (men) and 2.75% vs 1.03% (women); 0.59% vs 0.35% (ages 65‐69 years), 1.16% vs 0.65% (70‐74 years), 2.45% vs 1.19% (75‐79 years), 4.56% vs 1.86% (80‐84 years), and 8.71% vs 2.67% (≥85 years); 2.46% vs 1.05% (Whites), 1.87% vs 0.54% (Blacks), and 2.18% vs 0.58% (Asians). The prevalence of AD vs MCI in 2018 was highest in the US Northeast, especially in New Hampshire (3.25% vs 1.64%), Maryland (3.23% vs 1.45%) and New Jersey (3.43% vs 1.40%).

Conclusion

Among Medicare beneficiaries from 2008 to 2018, AD prevalence was generally stable, while MCI increased. Women, older age, White race, and Northeast region were associated with higher prevalence of AD and MCI in 2018.
Managing Your Own Wellness (MYOW): Intervention for improving wellness through dementia care partner’s self‐care
Authors: Ishado Emily , McKiddy Sarah , Rosser Aaron F , Sadak Tatiana
Published: December 2023

Background

Caring for a person living with dementia (PLWD) can be a stressful and straining experience for family/friend care partners (CP), often leading to an increased risk for adverse psychosocial and health outcomes (e.g., depression, anxiety, mortality). Engaging in self‐care can reduce these risks and improve health. Yet, comprehensive tools that measure self‐care as a dynamic concept in the context of dementia caregiving do not exist. “Managing Your Own Wellness” [MYOW] checklist was created and validated to capture dementia CP self‐care behaviors and to inform the development of a brief, tailored person‐centered intervention. The study’s objective was to pilot test this intervention, with the ultimate goal of informing a new generation of CP interventions that address the complex and wide range of self‐care needs.

Method

Nineteen primary dementia CPs completed the study and participated in the baseline visit to establish a self‐care goal, three weekly check‐in coaching visits with the interventionist, and a final exit interview at week four. Measures at baseline, week four, and week 12 included MYOW, well‐being scale, single item tool for perceived strain and stress, and screening tools for depression and anxiety. Participants completed daily tracking forms to report their engagement and perception of progress in their selected self‐care activity. All interviews were transcribed and coded using thematic content analysis. Study measures were evaluated using correlation analyses.

Results

CP’s increased engagement in self‐care activities and improved sense of well‐being were captured by quantitative measures. Qualitative analysis revealed themes involving a change in relationship dynamics, evolution of the sense of self, shift in internal personal perspective (acceptance) and its effects on CP behaviors (increased patience, less frustration), and perception of PLWD interactions (more cooperative).

Conclusion

MYOW intervention had high acceptability and demonstrated high potential for broad dissemination. CP engaged in developing and following through on personalized self‐care goals and in tracking their progress. The impact of self‐care is dynamic and multi‐faceted. Focusing on brief daily wellness‐related activities has mutual benefits for CP and PLWD. Future research should be focused on further simplifying intervention protocols and measures and evaluating the intervention with a larger diverse sample of CP.
Novel Pyrazinoindolones As Amyloid‐Beta Aggregation Inhibitors
Authors: Rao Praveen Nekkar , Hejazi Leila , Shakeri Arash
Published: December 2023

Background

Alzheimer’s disease (AD) is a devastating neurodegenerative condition which primarily affects the elderly population. One of hallmarks of AD is the accumulation of protein aggregates known as amyloid‐beta (Aβ) that promotes neurotoxicity and cognitive decline. Recent discoveries in the field led to the accelerated market approval of anti‐Aβ antibodies aducanumab and lecanemab. These are exciting discoveries. However, considering the cost and patient compliance issues with these biological therapies, discovering novel anti‐Aβ therapies that are based on small molecules is highly desirable due to several advantages over biological therapies including the ease of oral administration, reduced cost involved in bulk manufacturing and better stability on storage.

Method

A library of novel pyrazino[1,2‐a]indole‐1(2H)‐one derivatives were designed using the computational modeling software Discovery Studio Structure‐Based‐Design (Biovia Inc, San Diego USA). Then synthetic chemistry protocols were optimized to prepare small molecule library and were characterized by 1H and 13C NMR and Liquid Chromatography Mass Spectrometry studies. The anti‐Aβ activity of these novel molecules toward Aβ40 aggregation was evaluated by fluorescence spectroscopy using the thioflavin‐T based aggregation kinetic studies. In addition, the online web tool SwissADME was used to calculate the physicochemical properties of pyrazino[1,2‐a]indole‐1(2H)‐one derivatives to assess their drug‐likeness, blood‐brain barrier permeability and pharmacokinetics.

Result

A novel library of pyrazino[1,2‐a]indole‐1(2H)‐one derivatives were prepared by optimizing a four step or two step synthesis protocol starting from either phenylhydrazine or indole‐2‐carboxylic acid to afford pyrazino[1,2‐a]indole‐1(2H)‐one derivatives 5a–f. In the Aβ40 (5 μM) aggregation kinetics assay, they exhibited 14‐59% inhibition when tested at a range of concentrations (1, 5, 10 and 25 μM), demonstrating their anti‐Aβ properties. Their physicochemical properties suggest their drug‐likeness.

Conclusion

Structure‐activity relationship studies demonstrate that the fused tricyclic pyrazino[1,2‐a]indole‐1(2H)‐one is a suitable template to i) develop novel chemical tools to study and understand the mechanisms of Aβ40 aggregation and ii) discover novel small molecules as potential therapies for AD.
Incidence of Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) in the United States Medicare population
Authors: Zhang Haixin , Zhang Quanwu , Monfared Amir Abbas Tahami
Published: December 2023

Background

Alzheimer’s disease (AD) is a chronic, neurodegenerative condition. Mild cognitive impairment (MCI) is characterized by cognitive decline, without dementia. We aimed to estimate the incidence of AD and MCI among Medicare beneficiaries.

Method

Patients were identified from the US Center for Medicare and Medicaid Services (CMS) database using International Classification of Diseases (ICD) codes for AD (331.0, G30.9, G30.8, or G30.1,) and MCI (331.83 or G31.84). Both AD and MCI were identified using the search rule of 2 ICD codes ≥30 days apart ≤365 days from both Medicare fee‐for‐service (FFS: 2008‐2018) and Medicare Advantage (MA: 2015‐2018). US regions were derived using zip codes and categorized by National Center for Chronic Disease Prevention/Health Promotion regions. Yearly incidence was defined as the number of new cases of AD or MCI in each year divided by the population at risk in the year. Confidence intervals were not reported due to small intervals.

Result

The incidence of AD and MCI per 10,000 person‐years was 82.9 and 4.9, 80.3 and 7.4, 74.5 and 9.3, 69.8 and 10.9, 65.3 and 13.4, 62.8 and 15.8, 60.7 and 17.4, 65.5 and 20.7, 61.4 and 22.4, 56.0 and 22.9, and 52.2 and 23.2 spanning from 2008 through 2018, respectively. In 2018, the incidence of AD and MCI per 10,000 person‐years by demographic subgroups was: 43 and 21 for men and 59 and 25 for women; 16 and 10 among those aged 65‐69 years, 30 and 18 for ages 70‐74 years, 58 and 30 for ages 75‐79, 102 and 44 for ages 80‐84, 176 and 57 for age ≥85 years old; 56 and 26 for Whites, 38 and 13 for Blacks, and 43 and 15 for Asians. The incidence of AD and MCI per 10,000 person‐years in 2018 was highest in the US Northeast, especially in New Hampshire (77 and 39), Vermont (74 and 47), and New Jersey (73 and 33).

Conclusion

Among Medicare beneficiaries from 2008 to 2018, AD incidence generally decreased while MCI increased. Women, older age, White race, and Northeast region were associated with higher incidence of AD and MCI in 2018.
Chronic kidney disease is associated with cognitive dysfunction and cardiovascular remodeling in aged male and female Sprague‐Dawley rats
Authors: Santos Carla Rocha Dos , Grigorova Yulia N , McDevitt Ross A , Long Jeffrey M , Haghkar Mahdi , Wei Wen , Zernetkina Valentina I , Juhasz Ondrej , Morrell Christopher H , Rapp Peter R. , Sodhi Komal , Lakatta Edward G , Fedorova Olga V
Published: December 2023

Background

Cardiovascular diseases (CVD), including increased central arterial stiffness (CAS), accompany chronic kidney disease (CKD) development. An increase in pulse wave velocity (PWV), an index for CAS, is implicated in age‐associated changes in the brain and potentiates the development of CI in CVD and CKD in humans and animal models. The aim of this study was to determine whether inducing CKD accelerates the development of CI and CAS in aged male and female rats.

Method

Ten months‐old male and female Sprague‐Dawley rats were fed with 0.25% adenine diet to accelerate CKD (n = 10‐12; CKD‐male, CKD‐female) or regular diet (n = 8‐10; CNT‐male, CNT‐female) for 8weeks. Body weight (BW), blood pressure (BP), heart rate (HR), aortic‐PWV (aPWV), behavioral tests, blood urea nitrogen (BUN), creatinine and hematocrit were assessed at the endpoint. The anxiety‐like behavior was tested in open field test (OFT) and elevated plus maze (EPM). Morris water maze (MWM) and cross maze (CM) were used to test spatial memory. The data were analyzed using two‐way ANOVA.

Result

CKD development in both sexes was accompanied by kidneys enlargement, increase in BUN and creatinine, and reduction in hematocrit. In CKD‐male the kidney function was more compromised with higher levels of BUN and creatinine vs. CKD‐female (Table 1). CKD‐male had lower BW and SBP vs. CNT‐male (Table 1). CKD induced a reduction in HR, increase in aPWV and aortic weight in both sexes vs. respective CNT‐groups (Figure 1). Both CKD‐male and CKD‐female demonstrated a tendency of increase in path length to find the hidden platform in MWM, e.g., both sexes had numerically impaired spatial memory. CKD‐male spent less time in the center of OFT, a measure of anxiety, and loss of spatial memory, with a reduction of spontaneous alternation task assessed by CM. CKD‐female exhibited higher level of anxiety spending less time in open arm of EPM vs. CNT‐female (Figure 2).

Conclusion

CKD development in old male and female Sprague‐Dawley rats was accompanied by an increase in CAS, cardiovascular remodeling, and cognitive dysfunction. In CKD, CI affected different cognitive domains in the old males than in the age‐matched females.

Supported by NIA/NIH/IRP
Causal inference on strategies to increase conversational engagement for socially isolated older adults
Authors: Yuan Fengpei , Zhou Wenjun , Dodge Hiroko H , Morris Tyler , Zhao Xiaopeng
Published: December 2023

Background

Social isolation, characterized by a small social network and lack of contact, negatively impact the quality of life. Older adults are at an increased risk for social isolation, which is found to be a risk factor of cognitive decline and dementia. Enhancing social connectedness or interactions has been shown to be an effective intervention for slowing age‐associated cognitive decline and possibly delaying the onset of dementia. Here we aim to develop conversational chatbots which can provide engaging conversations with older adults with mild cognitive impairment (OAwMCI) to mitigate social isolation. To resemble human human interactions, chatbots have to adapt certain human strategies, such as empathy, during conversation.

Method

Our study utilized causal structural learning and causal inference approaches to examine the dialogue strategy for engaging OAwMCI. We analyzed transcriptions from a clinical trial, I‐CONECT (ClinicalTrials.gov #: NCT02871921), which involved semi‐structured conversations between facilitators and participants. By using emotion recognition in conversation and dialogue act modeling, we produced a time series data of state (participant’s emotions and length of utterance per conversation turn), intervention (facilitator’s conversational strategies), and outcome (participant’s following emotions and engagement). A R package, pcalg, was used to identify causal relationships between the state, intervention, and outcome variables.

Result

Graphical models implying causal relationships between certain factors were generated. Our analysis revealed that facilitators adjusted their dialogue strategies according to the participants' emotions and utterance. For example, facilitators expressed appreciation when a participant showed . Additionally, we found that the dialogue acts from facilitators influenced participants' emotions and engagement in the conversation. For instance, non‐opinion statements and yes/no questions from facilitators may affect participants’ verbal engagement and level of anger during the conversation.

Conclusion

Findings from this study are in line with real‐world human‐human conversation, and our next step is to explore how to use these findings to improve conversational chatbots. Future work shall also consider other crucial features into the state variable that might influence the dynamics of participants' status during the conversation, such as cognitive capacity and dialogue coherence. Our findings have the potential to inform the development of conversational tools and strategies to reduce social isolation among OAwMCI.
e‐FINGERPRINT Pilot Study: Assessing the feasibility of digital data collection and multidomain lifestyle guidance towards the prevention of cognitive decline and dementia
Authors: Giannakopoulou Parthenia , Majeed Azeem , Solomon Alina , Middleton Lefkos T , Kivipelto Miia
Published: December 2023

Background

The ongoing eFINGER‐PRINT Pilot Study is a is a pioneering virtual feasibility study to evaluate different methodologies for recruitment and digital phenotyping in the context of readiness cohorts. In addition, the pilot aims to test virtual cognitive and other tools in their ability to detect changes in cognitive performance and lifestyle parameters over time, and associations between changes across other key health outcomes. The one‐year study was initiated in May 2022.

Method

Cognitively unimpaired individuals (up to 500) aged 60+ years residing in London, were recruited through the Cognitive Health in Ageing Register for Investigational and Observational Trials (CHARIOT). Inclusion criteria include no dementia diagnosis, access to the internet and a suitable device and English competency with no significant visual or auditory disability. The study collects subjective demographics, comorbidities, and health behaviours, sleep, frailty, functional abilities, and subjective memory symptoms, through repeated 4‐monthly questionnaire surveys administered online. Longitudinal cognitive data were obtained via a validated online cognitive assessment platform, and included customised assessments shown to be sensitive to AD related cognitive decline. Furthermore, participants are invited to join a preventative multi‐domain lifestyle guidance, based on repeated self‐reported evaluations of modifiable risk factors and a healthy lifestyle index, using a mobile, application. By joining the application, participants receive also bi‐monthly online educational literature on dementia prevention and healthy ageing, including guidance on nutrition and physical exercise and are asked to complete a variety of e‐based mental activities, targeting cognitive domains, such as memory, mental agility, visuospatial, and attention.

Result

A minimum recruitment rate of 20% and a retention rate of 50% will provide a methodological template for the e‐FINGER PRINT study. Furthermore, participant feedback and experience will aid in optimising recruitment processes, user acceptability and sustainability of the selected digital tools. A low attrition rate will indicate a positive user experience.

Conclusion

The pilot study will inform the design of the eFINGER PRINT main study, a five years’ large‐scale virtual FINGER‐based study that will be conducted in Greater London (2023‐2028). Given the promise of economic sustainability, utility of e‐based tools for disease prevention can offer dramatic up‐scalability and allow for the implementation of a prescriptive medicinal approach.