bluuebunny/crossref_metadata_2025 huggingface dataset:
Collaborative Approach for Asian Americans and Pacific Islanders Research and Education (CARE): A recruitment registry for Alzheimer’s disease and related dementias, aging and caregiver‐related research
Authors: Park Van Ta , Meyer Oanh L , Tsoh Janice Y , Vuong Quyen , Bang Joon , Hinton Ladson , Gallagher‐Thompson Dolores , Kanaya Alka , Gansky Stuart , Grill Joshua D ,   Collaborative Approach for Asian Americans and Pacific Islanders Research and Education (CARE)
Published: December 2021

Background

There have been large investments in Alzheimer’s Disease and Related Dementias (AD/ADRD) research, but low AD/ADRD research participation from ethnically diverse individuals can hinder the facilitation and progress in the advancements of AD/ADRD prevention, treatment and care. The fastest growing racial group of older Americans at risk for AD/ADRD are Asian Americans and Pacific Islanders (AAPIs), but their research participation is limited. To address this disparity in AAPIs’ research participation, a recruitment registry, Collaborative Approach for AAPI Research and Education (CARE), was established to educate and engage AAPIs in AD/ADRD, aging, and caregiving related research in California, U.S.A. We will discuss an overview of CARE, completed/planned activities, and future vision.

Methods

CARE created a recruitment registry of 10,000+ AAPIs. CARE has 25+ community/research partners, many of whom serve on CARE’s Community Advisory Board, who help to a) ensure that the outreach/conduct adheres to the principles of cultural humility/appropriateness; b) provide overall guidance/feedback about the registry’s development; c) provide input about research findings; and, f) provide perspectives/suggestions on community engagement. Focus groups (N=14) with AAPI cultural groups were conducted to identify best strategies for recruiting/retaining AAPIs’ CARE participation and establishing effective processes for connecting participants to studies. Based on focus group data, Discrete Choice Experiment (DCE) surveys will be conducted in early 2021 to examine AAPIs’ preferences on recruitment messages/strategies.

Result

CARE’s theme is “Health Across the Lifespan”, which considers the intergenerational families and collectivist AAPI cultures. CARE’s full launch was on 10/15/20 and as of 01/09/21, 1,400 AAPIs have enrolled. CARE is promoting its use via CARE’s Brain Trust meetings and the National Institute on Aging. Several outreach materials have been developed including: AD/ADRD caregiver audio stories; animated video; flyers; community‐tailored presentations. CARE’s activities are available in five spoken languages (English, Mandarin, Cantonese, Korean, Vietnamese) and five written languages (English, Simplified Chinese, Traditional Chinese, Korean, Vietnamese).

Conclusion

CARE aims to meaningfully include AAPI in AD/ADRD/aging/caregiving‐related research; and, for CARE to serve as a national resource for ADRD prevention, caregiving, and treatment research. We envision CARE to become a national recruitment registry and expand to include additional AAPI languages.
Nutritional treatments for Alzheimer’s disease: A narrative review
Authors: Aschettino Liza A , Labyak Corinne A , Sealey‐Potts Claudia
Published: December 2021

Background

Knowledge is limited about ways to treat, manage and slow the progression of Alzheimer’s Disease (AD). It is suspected that there are potential nutrition‐related components that may contribute to the pathology of AD. This includes nutrient deficiencies and/or dietary factors that may lead to comorbidities, increasing the risk for development. Thus, many nutrient‐specific, dietary and medical food treatments are continually being researched. Some studies even combine both nutrient and dietary interventions to treat AD. The purpose of this review is to explore and discuss the efficacy of several macro‐ and micronutrients, antioxidants, dietary therapies and combined components to treat or slow the progression of AD while providing valuable insight into the role that nutrition may play in the treatment of this disease.

Methods

Using PubMed, Google Scholar, EBSCOhost and Science Direct, databases were searched using pertinent keywords. A total of 33 research articles were included, primarily consisting randomized, double‐blind, placebo‐controlled clinical human research trials with the addition of few animal studies. Full‐text studies in detail were obtained, assessed with data extracted and summarized.

Results

Overall, it was determined that folate in conjunction with Donepezil, may improve cognitive function and inflammatory markers. Omega‐3 fatty acids (FA) with ɑ‐lipoic acid may reduce cognitive and functional decline rates. Adequate B‐vitamin status is needed to obtain the benefits of omega‐3 FAs. Vitamin D supplementation and medical food Souvenaid may be considered for cognitive benefits in patients with AD. Medium‐chain triglyceride (MCT) supplementation is not yet supported. Antioxidant treatment is not recommended as it may accelerate cognitive decline. DASH, Mediterranean Diet, MIND and ketogenic diet therapy may be considered as dietary treatments in AD patients. Nutrient supplementation requires more research to determine appropriate dosages.

Conclusion

Alzheimer’s disease remains a major health concern to the aging public. The anti‐inflammatory properties, antioxidative and neuroprotective effects of several nutrition‐related treatments have been shown to be beneficial in combating the progression of this disease. Patient individualization must be considered prior to treating. It is recommended that future studies determine appropriate dosage amounts to minimize adverse effects.
Cognitive change by anxiety and depressive symptoms in subjective cognitive decline: An implication to prevent Alzheimer's disease
Authors: Ahn Sangwoo
Published: December 2021

Background

While anxiety and depressive symptoms frequently exist in subjective cognitive decline (SCD), how anxiety or depressive symptoms and their co‐existence differentially map onto particular cognitive domains is unknown among older adults with SCD. The purpose of this study was to evaluate longitudinal associations between baseline psychological symptoms (anxiety [A] and/or depressive [D] symptoms) and changes in global cognition, episodic memory, attention, language, and executive function.

Method

Data were from the National Alzheimer’s Coordinating Center for this longitudinal, observational study. A total of 1,401 older adults with SCD (ages: 74.0 ± 8.2 years) were assessed over 4.1 ± 2.4 years. Linear mixed‐effects regression models were used to evaluate longitudinal cognitive changes by baseline psychological symptoms among older adults with SCD. Reference was the group without any psychological symptoms (A–/D–).

Result

The presence of anxiety symptoms only (A+/D–) was not associated with any cognitive changes. Whereas, the presence of depressive symptoms only (A–/D+) was associated with a greater decline in episodic memory and executive function, cognitive domains that are affected early in Alzheimer’s disease. The presence of both anxiety and depressive symptoms (A+/D+) was associated with a greater decline in attention. No psychological symptoms predicted changes in global cognition and language.

Conclusion

Based on the finding that depressive symptoms predicted lower episodic memory and executive function, managing depressive symptoms may help protect against cognitive decline more typical of early Alzheimer’s disease among older adults with SCD.
Association of social integration with cognitive status: results from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study
Authors: Calmasini Camilla , Swinnerton Kaitlin N , Zimmerman Scott C , Peterson Rachel L , George Kristen M , Gilsanz Paola , Hayes‐Larson Eleanor , Mungas Dan M , Whitmer Rachel A , Glymour M Maria
Published: December 2021

Background

Lack of strong social ties is associated with numerous morbidities including adverse late‐life cognitive outcomes. Prior work on social integration and cognition has been conducted in predominantly White cohorts. We evaluated the relationships between social integration and cognition in diverse older adults from major racial/ethnic groups in the United States using data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study.

Method

KHANDLE is a multi‐ethnic study of 1712 Kaiser Permanente Northern California members age 65+. Social integration was assessed using the Berkman‐Syme Social Network Index. A score ranging from 0 to 6 was calculated by assigning 1 point for each of the following domains: being married/partnered, volunteer activity, having monthly contact with children, relatives, and friends and daily contact with confidante (Figure 1). Cognition included three domains derived from the Spanish and English Neuropsychological Assessment Scales: verbal episodic memory (for White, Black and Latino participants), semantic memory and executive function. Covariate‐adjusted linear mixed‐effects models estimated a single association of social integration with cognition applicable to all three cognitive domains for the full sample and by race/ethnicity. Core models adjusted for age, gender, race, and education (years); expanded models further adjusted for variables that could either be determinants or consequences of social integration, including weekly alcohol use, average score for combined activities of daily living (ADL) and instrumental ADL, and income. We repeated these analyses using frequency of contact with confidante as the primary exposure.

Result

Higher social integration score was associated with better cognition in core covariate‐adjusted models (β=0.065 (0.039, 0.091)); the association attenuated slightly when adjusting for expanded covariates (β=0.045 (0.019, 0.071)). In race‐stratified core models, higher social integration scores were associated with better cognition among Asian, Black, Latino, and White participants. In expanded models patterns were similar, but the association remained statistically significant only for Black participants (Table 1). Seeing a confidante daily was associated with higher cognition in the pooled model and for Asian participants (Table 2).

Conclusion

Our findings suggest that social integration and seeing a confidante daily were associated with better cognition across the four racial/ethnic groups.
Risk of falling in mild cognitive impairment: Relationships with diminishing regional cerebral metabolism and clinical parameters in a long‐term prospective longitudinal multi‐center study
Authors: Zhang Lorena , Liu Stephen , Silverman Daniel H
Published: December 2021

Background

We recently identified visual cortex and cerebellar vermis as the cortical and non‐cortical brain areas, respectively, in which declining metabolism was most predictive of falling (Soc. Nucl. Med. Molec. Imaging, 2021.) We now describe alterations in relationships between rates of change in their metabolism, and cognitive/functional performance.

Method

Of 226 FDG‐PET brain scans from 113 Alzheimer’s Disease Neuroimaging Initiative MCI subjects analyzed, 122 were from subjects (MCI‐F ,n=61) suffering a fall subsequent to baseline PET, while 104 were from age‐matched subjects (MCI‐N, n=52) having no documented falls. MCI‐F scans were taken from baseline and last time point preceding date of first fall; MCI‐N scans were taken from baseline and last time point available. Magnitudes of regional metabolism in standardized volumes of interest (sVOI’s) were normalized to metabolism of each subject’s pons. Rates of longitudinal change were calculated as the interval difference in magnitudes between each sVOI pair divided by interval time. Significance of associations between metabolic changes and changes in overall cognition (MMSE), function (FAQ) and four individual domain scores were assessed following Bonferroni‐type statistical correction for multiple comparisons.

Result

In the vermis of MCI‐N subjects, changes in metabolism correlated with changes in overall cognition and function (p=0.00007, p=0.00003, respectively); among individual cognitive domains, metabolic changes most significantly correlated with changes in visuospatial (p=0.005) and language (p=0.001) scores. Interestingly, among MCI‐F subjects, vermis metabolism declined severalfold faster than in their MCI‐N counterparts, while significant associations with changes in MMSE and FAQ (both p>0.30) as well as with visuospatial changes (p>0.99) were entirely lost, yet language changes remained strongly correlated (p=0.00004). Similarly, in bilateral visual cortex of MCI‐N, changes in metabolism correlated with changes in MMSE and memory, and those associations were lost in MCI‐F.

Conclusion

Metabolism of cerebellar vermis ‐ critical for maintenance of upright posture and locomotion ‐ and of visual cortex ‐ known to diminish in patients with Lewy body involvement (associated with orthostatic hypotension and gait disturbance, both in turn increasing fall risk) ‐ not only underwent accelerated decline, but metabolic decline also became dissociated from cognitive and functional performance in MCI‐F, prior to their first documented fall.
Clinical factors contributing to functional change over time in individuals with subjective cognitive concerns and mild cognitive impairment
Authors: Lin Pinghsiu , LaMonica Haley , Naismith Sharon L , Mowszowski Loren
Published: December 2021

Background

Accumulating research suggests individuals with subjective cognitive concerns (SCC) and Mild Cognitive Impairment (MCI) experience subtle but noticeable functional changes, despite diagnostic criteria emphasising predominantly intact daily functioning to differentiate them from more severe stages of decline, i.e. dementia. This study investigates how factors associated with cognition, general health, and psychosocial wellbeing relate to functional change longitudinally in older adults with early‐stage cognitive change.

Method

One hundred and thirty‐seven participants with SCC or MCI (mean age=70.4 years, SD=8.0) completed standardised neuropsychological, medical and psychosocial assessments, and the self‐report Healthy Brain Ageing ‐ Functional Assessment Questionnaire (HBA‐FAQ) at baseline and again at follow‐up at least one year later (mean time to follow‐up= 25.5 months, SD=8.0). Correlational and linear regression analyses were used to explore relationships between subjective functional change over time and cognition, general health, and psychosocial wellbeing, where p was set at .05.

Result

Older people with SCC and MCI reported a similar amount of functional change (p = .13) and were therefore analysed as one ‘at risk’ group. Overall, greater subjective functional change over time was significantly and most markedly correlated with poorer baseline cognitive performance on tests of new learning (r = ‐.23), memory (r = ‐.25), processing speed (r = ‐.25), and cognitive flexibility (r = ‐.21), as well as poorer baseline psychosocial wellbeing including subjective disability (r = .56), quality of life (r = ‐.54), sleep quality (r = .29), mood disturbance (r = .51) and subjective memory complaints (r = .51). Of these factors, greater subjective memory complaints and greater mood disturbance at baseline significantly predicted increased functional change at follow‐up, accounting for 9.7% and 3.3% respectively of the unique variance in the model.

Conclusion

These results suggest that functional change over time is evident in older adults with early‐stage cognitive change and is associated with poorer cognition and psychosocial wellbeing. This has important implications for early intervention, as this research highlights key clinical factors predictive of functional decline that clinicians can look out for when assessing older adults in primary practice. Targeted early intervention and management strategies may then help to maximise and maintain day‐to‐day functioning.
Circulating cystatin‐C is associated with dementia in a racial and ethnically diverse cohort: An interaction decomposition analysis
Authors: Higgins Cesar , Ware Erin B , Hicken Margaret , Zawistowski Matthew , Bakulski Kelly M
Published: December 2021

Background

Cystatin‐C has an important role in the pathogenesis of dementia, as evidenced by expression in the brain and co‐localization with beta‐amyloid deposits. Circulating Cystatin‐C may be directly implicated in neurodegeneration, or the result of a compensatory mechanism of neuroprotection. Our study aims to understand the relationship between circulating Cystatin‐C and dementia, and to test the interaction between Cystatin‐C and race/ethnicity.

Methods

We performed a cross‐sectional analysis of serum Cystatin‐C levels with dementia and cognitive impairment non‐dementia (CIND) in two waves (2006 and 2008) of the Health and Retirement Study (n=9,984). We used Poisson regression with robust variance to estimate the interactive effect of race/ethnicity and Cystatin‐C >75th on dementia. We calculated three measures of interaction in the additive scale: the excess risk due to interaction (RERI), the attributable proportion, and the synergy index (SI). We decomposed the interaction to calculate the percentage of the excess risk attributable to the effects of race/ethnicity and Cystatin‐C alone.

Results

African Americans and Hispanics had higher levels of Cystatin‐C at every decade of life except for the 80s with respect to Whites (see Figure 1). The prevalence ratio for dementia among African Americans with levels of Cystatin‐C >75th was 7.33 (95%CI: 5.43, 9.89) times of White Americans with Cystatin‐C <75th. A RERI of 1.89 (95%CI: ‐0.17, 3.95) indicates more than an additive interaction; and attributable proportion of 0.26 (95%CI: 0.02, 0.50) suggests than roughly a quarter of the excess risk was due to the interaction of both race and Cystatin‐C; and a synergy index of 1.43 (95%CI: 0.97, 2.10) provided evidence of synergism between the two exposures. We found 26% (95%CI: 2%, 50%) of the excess risk among the doubly exposed group (i.e., African Americans with levels of Cystatin‐C >75th) was attributable to the interaction between Cystatin‐C and race. Similar patterns were observed for Hispanics in relation to Whites.

Conclusion

Elevated levels of circulating Cystatin‐C are implicated in impaired cognition, and the association between Cystatin‐C and cognition varies dramatically by race/ethnicity.
Circadian rhythm disturbance in agitation of Alzheimer's disease
Authors: Rosenberg Paul B. , Outen John D. , Spira Adam P. , Zipunnikov Vadim , Wanigatunga Sarah K. , Wu Mark N.
Published: December 2021

Background

Agitation in Alzheimer’s Disease (Agit‐AD) is a major cause of burden for caregivers and may be driven by disrupted circadian rhythms and sleep. The circadian clock that generates these rhythms regulates patterns in mood, wakefulness, and other physiologic processes, such as body temperature and hormone levels. This project aims to examine if agitated AD subjects (AgitAD+) exhibit delayed circadian phase and lower rhythm strength compared to non‐agitated AD subjects (AgitAD‐) and healthy controls. We will additionally compare sleep amount, sleep quality, and degree of sleep disordered breathing among AgitAD+ vs. AgitAD‐ and healthy controls.

Method

Participants completed wrist actigraphy for one week to quantify rest/activity rhythms and sleep; consumed an ingestible, disposable temperature sensor for 1‐2 days to quantify core body temperature rhythms; and completed a single night of home sleep testing (HST). Inclusion criteria were diagnosis of AD and age 55‐90 years, and exclusion criteria include seizures, significant tremors, delirium, CPAP use for sleep apnea, restless legs syndrome, and circadian rhythm disorders. Due to the COVID‐19 pandemic, we implemented hybrid visits with telemedicine to limit in‐person interactions.

Result

To date, 26 participants have enrolled. There were no statistically significant differences observed in actigraphic sleep parameters between groups (Table 1). However, AgitAD+ participants had lower levels of activity in the morning and greater activity in the afternoon and evening (Figure 1). After adjustment for age, agitation was associated with lower activity in the morning and a trend towards greater activity in the afternoon and evening (Figure 2). This preliminary finding may suggest that AgitAD+ participants express lower and delayed activity rhythms. HST results show a trend toward less REM sleep and longer initial REM latency in the AgitAD+ group (Table 2). Updated results will be presented at AAIC (estimated 6‐10 additional participants).

Conclusion

This study could provide evidence for CRD/sleep disturbance as a driver of Agit‐AD and could identify Agit‐AD subtypes who are most likely to from chronobiotic or sleep interventions.
Extracellular vesicular lipids as biomarkers for the diagnosis of Alzheimer’s disease
Authors: Su Huaqi , Rustam Yepy H. , Masters Colin L. , Makalic Enes , McLean Catriona , Hill Andrew F. , Barnham Kevin J. , Reid Gavin E. , Vella Laura J.
Published: December 2021

Background

An increasing number of studies have revealed that dysregulated lipid homeostasis is associated with the pathological processes that lead to Alzheimer’s disease (AD). If changes in key lipid species could be detected in the periphery, it would advance our understanding of the disease and facilitate biomarker discovery. Global lipidomic profiling of sera/blood however has proved challenging with limited disease or tissue specificity. Small extracellular vesicles (EV) in the central nervous system, can pass the blood‐brain barrier and enter the periphery, carrying a subset of lipids that could reflect lipid homeostasis in brain. This makes EVs uniquely suited for peripheral biomarker exploration.

Method

To determine the potential of EV lipids as biomarkers, we isolated brain‐derived EV (BDEV) from frontal cortex tissue (Vella, et al. JEV. 2017) and performed quantitative mass spectrometry based lipidome analysis (Rustam and Reid. Anal. Chem. 2018). We developed and optimised methods to isolate pure EVs from plasma while minimising co‐isolation of lipoproteins. To confirm the identity of EVs, we are using various techniques including western blot, nanoparticle tracking analysis and transmission electron microscopy. We are mining the mass spectrometric data for brain‐specific signals.

Result

Western blot analysis showed successful isolation and enrichment of BDEV from brain tissue. TEM revealed the typical round and cup‐shaped EV morphology with vesicle size being 50‐150nm. A total of 692 lipids were identified and quantified. Enrichment of glycerophosphatidylserine (PS) lipids, especially the ether PS lipids, alkyl‐ and alkenyl‐, were observed in BDEV. Remodeling in phosphatidylethanoamine (PE) lipid class and polyunsaturated fatty acyl containing lipids (PUFA‐) was observed in AD BDEV. The preliminary experiments demonstrate successful isolation of pure EVs from plasma. Lipidomic and proteomic analysis suggests that plasma EVs contain brain‐specific signals.

Conclusion

We, for the first time, characterized the lipid composition of EVs in human frontal cortex. BDEVs offered improved detection of dysregulated lipids in AD and these lipids have previously been reported to play key roles in AD pathogenesis, suggesting BDEV provide a readout of lipid dysregulation in AD and highlighting the potential use of these lipids as disease biomarkers in the periphery.
Specific affective dimensions are associated with a faster rate of cognitive decline in older adults
Authors: Soleimani Laili , Beeri Michal Schnaider , Grossman Hillel , Sano Mary , Zhu Carolyn W
Published: December 2021

Background

The relationship between different affective presentations and cognitive outcome is poorly understood and may elucidate subgroups of patients who are more at risk for decline. Here we utilized longitudinal data from subjects ≥ 60 years, enrolled in the National Alzheimer’s Coordinating Center (NACC) study for an average of 5 years and who were not demented at baseline to investigate the relationship between affective dimensions and global cognition and specific cognitive domains over time.

Method

Subjects [n=17,385; mean age= 73.73 (SD= 7.72); 59.20% female] completed the 15‐item geriatric depression scale (GDS‐15) and a broad neuropsychological battery at baseline, and approximately every 12 month follow ups. Cognitive domains included episodic memory, attention, executive functions, and language. Global cognition averaged the z‐scores of the four domains. Affective dimensions were defined based on GDS‐15 factors previously described, and included dysphoric mood, Withdrawal‐Apathy –Vigor (WAV) , anxiety, hopelessness and memory complaint. Linear mixed models (LMM) analysis was used to assess associations between the five affective dimensions with global cognition and each cognitive domain. Analyses adjusted for baseline age, sex, race/ethnicity, years of education, baseline Functional Assessment Questionnaire (FAQ), indicators for history of diabetes, hypertension, and hypercholesterolemia.

Result

At baseline, our sample had low reported depressive symptoms (GDS‐15=1.66; SD= 2.23) and were non‐demented (MMSE= 28.34; SD=2.01). Reported subjective memory complaint and hopelessness were associated with faster decline in all cognitive domains (all p<0.001) and , attention and executive function (all p<0.001), but not with episodic memory or language. In contrast, dysphoria and anxiety were not associated with a faster decline in global cognition or any of the cognitive domains.

Conclusion

In our large clinical sample of initially non‐demented older adults, different affective dimensions had different degree of associations with the rate of cognitive decline, suggesting distinct pathophysiology and need for more targeted interventions.
Pandemic times: Perception of online cognitive stimulation groups in in older adults with cognitive complaints
Authors: Berardo María Celeste , Martínez Claudia Patricia Múnera , O'Neill Santiago , Sorondo Juan , Sanjurjo Natalia Sierra
Published: December 2021

Background

Cognitive reserve is a factor that can modify the clinical expression of different degenerative diseases (Stern, 2012). Some studies have shown that the older who engage in mental activities have a better overall functioning (Aguirre et al., 2013). The Institute of Neurosciences of the Favaloro Foundation offers 6 hours weekly cognitive stimulation groups to patients with cognitive complaints. In Argentina, due to lock down to decrease SARS‐COV 2 infection, the cognitive stimulation groups began to be offered online. The aim of this study is to analyze how our patients perceive the impact of the isolation after 9 months of online cognitive stimulation workshops.

Method

85 patients with mild executive‐attentional impairments, between 47 and 85 years old, answer a satisfaction questionnaire after attending 9 months to an online cognitive stimulation group. In these groups, patients connected twice a week through the virtual platform Google Meet. After this time, the patients were asked to answer a self‐administered questionnaire, prepared ad hoc. The satisfaction questionnaire consisted of a series of questions about the perceived changes in cognitive performance, emphasizing how they helped to cope with isolation. The study is a descriptive statistical analysis.

Result

72.9% of the participants reported being satisfied with online cognitive stimulation, with 77.6% believing that it was highly effective. 85.9% indicated that the isolation became more bearable thanks to the assistance. Regarding the perception of performance, 36.5% reported that their performance is better than before, while 33% register stability in their cognitive ability.

Conclusion

the patients perceived that online cognitive stimulation allowed positive changes in cognitive performance, making isolation more bearable. In this way, we can conclude that the isolation forced us to develop new strategies and activities of rehabilitation that are likely to continue to be used in the future.
Potential contributions of MRI and blood‐based biomarkers for cognitive status classification based on cognitive performance examinations
Authors: Farina Mateo , Saenz Joseph , Crimmins Eileen M.
Published: December 2021

Background

The global burden of dementia is growing from 50 million people in 2020 to 150 million in 2050 (World Health Organization). Health researchers often use national survey studies to understand the social and population dynamics of dementia. Many of these studies have relied on classification algorithms based on cognitive performance exams such as the MMSE and MOCA. However, researchers are concerned about misclassification leading to incorrect conclusions about dementia in the population. This study assesses how the addition of MRI markers, along with blood‐based biomarkers, would improve cognitive status classification based on cognitive performance exams.

Method

We use the data from the Alzheimer’s Disease and Neuroimaging Initiative (ADNI) to assess whether MRI measures (whole brain volume, hippocampal volume, and ventricle volume) along with plasma Aß and P‐Tau improve cognitive status classification accuracy, net of MMSE scores. To assess improvements, nested multinomial logistic regression equations adjusting for sex, age, and APOE alleles are used. In total, we have total of 1,442 respondents.

Results

We found marginal improvements in cognitive status classification when structural MRI measures and blood‐based biomarkers were included compared to only MMSE scores. The R2 for model with only MMSE (0.401) increased when both structural MRIs, and plasma Aß and P‐Tau were added (0.445, an approximately 10% improvement). Furthermore, while structural MRI measures and blood‐based biomarkers alone did explain a modest amout of variability in dementia status classification (R2 of .182 and 142, respectively), models with MMSE scores alone had by far the largest explanatory power at .401.

Conclusion

While MRI markers and blood‐based biomarkers may lead to novel insight in understanding how brain pathology leads to cognitive impairment, their application to improving cognitive status classification in survey research may be more limited. Our findings do not show large improvements in cognitive status classification when including them in our predictive models of cognitive status classification. Additionally, the marginal improvement may not justify the costs associated with data collection in large nationally representative datasets.
Brain‐targeted intranasal formulation of Centella asiatica: A potential strategy for treating Alzheimer’s disease
Authors: Haroon Hajira Banu B , Mukherjee Dhrubojyoti , Jayaraman Anbu
Published: December 2021

Background

A major drawback associated with the conventional AD therapy is the inability of drugs to cross Blood Brain Barrier (BBB). Although, many drugs show potential to dissolve amyloid protein in vitro, only few mimics this action in vivo due to hindrance by BBB. One such drug is Centella asiatica containing asiaticoside that is proven to dissolves amyloid protein in vitro but lacks in vivo effects.

Method

The study was designed to develop a nasal formulation of an herbal drug (Centella asiatica) using brain targeted polymers to bypass the BBB to enhance the penetration of Centella in the brain.The extract of C. asiatica was first encapsulated into β‐ cyclodextrin by acid‐base precipitation method. These particles were nanonised and encapsulated into thiolated eudragit (TE) by ionic gelation method. The nanoparticles were characterized by FTIR, XRD, DLS, SEM, AFM and Ex ‐ vivo permeation studies. MTT assay was performed using Human Umbilical cord Vein Endothelial Cells (HUVECs) mimicking Blood‐Brain‐Barrier (BBB) to establish the safety and permeability of NPs. Further, the targeting efficacy was confirmed by molecular docking studies against receptors Sphingosine‐1‐Phosphate receptor 1 and Low‐density lipoprotein Receptor‐related Protein associated with BBB.

Result

FTIR and XRD studies confirmed encapsulation of Centella into beta cyclodextrin and TE. Nanoparticle characterization confirmed the size and stability of the particles with zeta potential of −10.43 mV and Pdi of 0.260. NPs showed no signs of nasal ciliotoxicity and had good permeation of 88.44 ± 2.65 % (Mean ± SD, n=3) at 8h across nasal mucosa. MTT assay showed that the nanocomposite had lesser toxicity and better permeability compared to free drug (IC50 of Centella – 269.1 μg/mL and IC50 of nanoformulation – 310.625 μg/mL). The affinity of polymer to the receptors associated to BBB was proved by docking studies proves the ability of polymer‐based NPs to concentrate in brain post nasal administration.

Conclusion

The study successfully showed that the NPs containing Centella had better permeability across BBB that could be beneficial in treating AD when administered intranasally.
A polygenic risk score for the prediction of Alzheimer's disease in rural‐dwelling older adults in China
Authors: Hou Tingting , Liu Keke , Liu Cuicui , Cong Lin , Wang Yongxiang , Du Yifeng , Qiu Chengxuan
Published: December 2021

Background

Polygenic risk score (PRS), a weighted sum of the risk alleles of single nucleotide polymorphisms (SNPs), has been developed to predict Alzheimer’s disease (AD) among different ethnic populations. However, such a PRS is not available among the Chinese elderly population. We sought to develop a PRS for AD and further evaluate its predictive ability among rural‐dwelling older adults.

Method

This population‐based study included 4691 participants (age ≥65 years; 57.3% women) who were examined in 2018;of these, 2089 had been previously examined and diagnosed as free of dementia in 2014‐2015.We performed multiplex PCR assay to detect 58SNPs. AD was diagnosed following the NIA‐AA criteria. We applied logistic models to the 2018 data for the cross‐sectional SNPs‐AD associations, and identified candidate risk SNPs potentially associated with AD risk (p<0.30). The area under the ROC curve (AUC) was calculated to evaluate its discriminative ability. Cox models were employed to examine the longitudinal PRS‐AD association using the follow‐up data. We used C‐index to assess the predictive ability of the model. Finally, we conducted the internal validation of the model using bootstrap methods.

Result

In the cross‐sectional analysis (n=4691, 181 AD cases), 17 risk SNPs were identified for the PRS. A high PRS (>75th vs. <25th percentile) was associated with an age‐ and sex‐adjusted odds ratio of 2.62 for AD (95% CI: 1.65‐4.25); The AUC of PRS alone to discriminate AD was 0.597 (0.554‐0.638); when adding age and sex, AUC increased to 0.80 (0.763‐0.837). Of the 2089 baseline dementia‐free participants, 85 developed AD during the 4‐year follow‐up period. A high PRS (>75th vs. <25th percentile) was associated with a2.07‐fold risk of AD (1.12‐3.81) after adjusting for age and sex; The C‐statistic for AD prediction was improved from 0.783 to 0.826 when adding the PRS to the base model of age, sex, and education. Calibration plots showed good performance of the model for predicting the 3‐year risk of AD.

Conclusion

Polygenic risk score that incorporates common genetic variants is associated with an increased AD risk in Chinese elderly population. The PRS may help identify individuals at risk for AD.
Development of a healthy lifestyle index within a multidomain intervention aimed at prevention of cognitive impairment and dementia, and its association with cognition: Results from the FINGER trial
Authors: Barbera Mariagnese , Lehtisalo Jenni , Rissanen Heta , Hannukkala Roosamari , Ngandu Tiia , Solomon Alina , Laatikainen Tiina , Strandberg Timo , Antikainen Riitta L , Tuomilehto Jaakko , Hänninen Tuomo , Soininen Hilkka , Kivipelto Miia
Published: December 2021

Background

Given the complex and multi‐factorial aetiology of dementia, preventive interventions targeting several risk‐factors simultaneously and tailored on specific risk‐profiles are likely to be most beneficial. To date, trials testing lifestyle‐ and vascular‐based multidomain interventions for dementia and cognitive decline prevention have shown inconsistent results. In particular, achieving sufficient level of intervention intensity, accurately assessing adherence, and identifying the optimal target population have been highlighted among the key challenges. Within FINGER, the first large trial showing the efficacy of a multidomain intervention in preventing cognitive decline, we aimed to develop a Healthy Lifestyle Index (HLI) as a potential easy‐access indicator of adherence, and to assess its association with cognition.

Method

The HLI (score 0‐24) was developed based on a brief set of self‐reported questions collected at baseline, 12, and 24 months within the FINGER trial (N=1260) and across four lifestyle components: physical activity, diet, smoking and alcohol, and social and cognitive activity. The FINGER cognitive outcomes were the overall z‐score from a Neuropsychological Test Battery (NTB, 14 tests, primary outcome) and the z‐scores of the NTB cognitive domains (secondary outcomes). Linear mixed‐models repeated‐measures with maximum likelihood estimation were used to assess the effect of the intervention on change in the HLI and associations between HLI and cognition over the 2‐year study period.

Result

The intervention led to an increase in HLI (P<0.001). At baseline, the HLI was directly associated with the overall NTB z‐score (b=0.024; 95% CI: 0.014‐0.033; P<0.001) and individual cognitive domains. Baseline HLI was significantly associated with 2‐year changes in the NTB z‐score (0.006; 95% CI: 0.003‐0.010; P<0.001), as well as the memory domain. Changes in HLI were not significantly associated with 2‐year changes in cognitive outcomes.

Conclusion

The FINGER HLI may potentially help measure and monitor adherence to multidomain interventions aimed at prevention of cognitive decline. Being developed as an easy‐access tool, its application could be especially relevant for those settings where more complex assessments are not feasible, such as implementation trials in clinical practice, and primary care in particular. More evidence is needed to determine its efficacy in predicting response to such interventions.
Effectiveness of home‐based telerehabilitation in mild to moderate Alzheimer’s disease: A randomised controlled study
Authors: Menengiç Kübra Nur , Yeldan İpek , Cınar Nilgun , Şahiner Türker AH
Published: December 2021

Background

The COVID‐19 pandemic has made it necessity that rehabilitation services are provided remotely to patients. These process required a transformation in healthcare. The aim of this study was investigate the effectiveness of the home‐based online supervised exercise program in Alzheimer’s disease (AD). To our knowledge, this is the first study to report the results of real‐time supervised physical exercise telerehabilitation program in AD.

Method

Eighteen subjects with early‐middle stage of AD were randomised into 2 group as telerehabilitation group (TG; mean age: 77.7 ± 5.29 years; 7 Female, 3 Male) and control group (CG; mean age: 78.5 ± 7.07 years; 5 Female, 3 Male). Our primary outcome was Mini‐Mental State Examination (MMSE), seconder outcomes were Timed Up&Go (TUG), One‐leg Balance Test (OLBT), Functional Independence Measure (FIM), Geriatric Depression Scale‐Short Form (GDS). The 6‐week motor‐cognitive dual‐task exercise training was performed online and under the supervision of physiotherapist through videoconference. No physical or cognitive intervention was applied to the control group for 6 weeks. Subjects were assessed before and after the treatment. In statistical analysis, the change in the outcome scores was calculated (∆ = last measurement‐first measurement), the difference between the groups was performed with the Mann Whitney‐U Test in SPSS 22.0. Trial’s protocol is registered with Clinicaltrials.gov under number NCT04606251.

Result

There was a significant difference between TG and CG in favor of TG in MMSE, TUG, FIM and GDS (p<0,05); There was no significant difference between groups in OLBT (p>0,05). Statistical results have been showed in Table 1. No safety problem was observed during the treatment. All subjects were completed the study, there was a high adherence to treatment.

Conclusion

Physical exercise treatment with telerehabilitation was feasible, safe and well‐accepted by people with early‐middle stage of AD. Online‐supervised exercise program can improve cognitive function, functional mobility, independence and reduce depressive symptoms.
Evaluating the importance of historical address histories in an air pollution and dementia study
Authors: Leary Cindy S , Hajat Anjum , Fitzpatrick Annette L , Park Christina , Ilango Sindana , Adam Claire , Kaufman Joel D , Semmens Erin
Published: December 2021

Background

Evidence linking long‐term air pollutant exposures with dementia‐related risks is increasing. Changes in the brain may occur decades before diagnosis, and studies assessing the effects of air pollution on dementia should account for participant residential history to reduce exposure misclassification. Using the Ginkgo Evaluation of Memory Study (GEMS), we evaluated cumulative PM2.5 and NO2 exposure on dementia risk both with and without historical residential addresses.

Method

GEMS was a randomized trial of 3,069 participants in Hagerstown MD, Pittsburgh PA, Sacramento CA, and Winston‐Salem NC from 2000‐2008. Residential historical addresses were obtained through LexisNexis, a company constructing address histories from public databases. PM2.5 (1980‐1999) and NO2 (1990‐1999) cumulative exposures were calculated for each participant from a spatio‐temporal model in two ways: 1) using residential address histories reconstructed from LexisNexis addresses from 1980‐1999 (Figure 1), and 2) assuming participants lived from 1980‐1999 at the address documented during the GEMS baseline visit (2000‐2002). Hazard ratios from Cox models of all‐cause dementia, Alzheimer’s disease (AD), and mixed vascular dementia (VaD/AD) were compared across both sets of cumulative PM2.5 and NO2 estimates. Models were adjusted for age, study site, randomization year, gender, treatment group, neighborhood deprivation index (NDI), education, smoking status, smoking pack years, passive smoking exposure and apolipoprotein E4 (APOE4) status.

Result

Hazard ratios based on the LexisNexis historical addresses were generally larger than those from analyses without residential histories (Figure 2). The largest attenuation in effect after eliminating address history was for participants with vascular dementia either with or without AD (VaD/AD). An approximate interquartile range (IQR; 3 µg/m3) increase in 10 year mean NO2 exposure was associated with a 39% (95% CI: 7%, 81%) greater risk of mixed VaD/AD, but this decreased to 25% (95% CI: ‐7%, 66%) without histories. Similarly, an IQR (2 µg/m3) increase in 20 year PM2.5 was associated with a 19% (95% CI: 4%, 36%) greater risk of all cause dementia compared to 14% (95% CI:‐1%, 31%) without the historical addresses.

Conclusion

For epidemiological studies aiming to quantify long term place‐based exposures related to dementia risk, utilizing residential address databases may reduce misclassification in exposure assignments.
Quantified analysis of Aβ plaques and microglia from in vivo cohort of patients with idiopathic normal pressure hydrocephalus
Authors: Luikku Antti J. , Rauramaa Tuomas , Nerg Ossi , Koivisto Anne M. , Junkkari Antti , Martiskainen Henna , Soininen Hilkka , Hiltunen Mikko , Leinonen Ville
Published: December 2021

Background

Alzheimer’s pathologic change is frequently observed among patients with idiopathic normal pressure hydrocephalus (iNPH). Amyloid‐beta (Aβ) plaques and pathologic tau deposits in vivo are the hallmarks of neuropathologically verified AD, but correlation of Aβ plaque amount to cognitive decline remains controversial. The microglia reaction related with the brain Aβ pathology is under intense research and may modulate the toxicity of Aβ accumulation. Our aim is to characterize Aβ pathology and load in detail and evaluate microglia reaction related with the plaques and their correlation with clinical outcome.

Method

51 patients were shunted for iNPH between 9/2010 and end of 2017 with frontal cortical biopsy positive for Aβ. Aiforia create‐machine learning (ML) software was used on whole slide images (WSI) of ionized calcium binding adaptor molecule 1 (Iba1)/Aβ stained biopsies. ML was used to recognize Aβ area and Iba1 stained microglia somas. Clinical Dementia Rating global score (CDR‐GS) and Alzheimer’s clinical syndrome (ACS) were evaluated retrospectively at the end of the median follow‐up of 7.6 years (range 4.1‐ 14) during which 40 patients died.

Result

During the follow‐up 19 patients were diagnosed with Alzheimer’s clinical syndrome. Trained image analysis yielded recognition precision for tissue, Aβ and microglia somas with 0.99, 0.98, and 0.96, respectively. Percentage of Aβ area, microglia soma density and reactive microglia within 25 µm of Aβ plaques were acquired. In univariate analysis, preoperative MMSE was significant predictor of CDR‐GS (p < .001) and ACS (p < .01). In multivariate analysis, high preoperative MMSE predicted lower CDR‐GS on follow‐up (OR 0.74 [0.63‐0.85]) and lesser development of ACS (OR 0.86 [0.75‐0.99]). Among demented subjects, there was a trend of higher Aβ area density (median 2.4 % for CDR‐GS 0.5 and 10.1 % for CDR‐GS 3), and reactive microglia (median 84 for CDR‐GS 0.5 and 178 for CDR‐GS 3).

Conclusion

Higher Aβ load and reactive microglia might predict worse cognitive outcome and dementia. As additional patients will be analyzed during spring 2021, we will expect this trend to turn significant. Good baseline cognitive performance seems to protect from later development of Alzheimer’s clinical syndrome and dementia among iNPH patients.