bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of COVID‐19 Lockdown on Dementia Caregivers in the U.S.
Authors: Bullard Breanna M , Merrilees Jennifer , Wang Gene , Levenson Robert W
Published: December 2022

Background

In response to the COVID‐19 pandemic, mandated state lockdowns in the U.S. profoundly changed day‐to‐day life for many individuals providing informal care for a person with dementia or mild cognitive impairment. The present study explored changes in caregiver burden, depression, and anxiety associated with lockdown.

Method

We used questionnaire data collected as part of a randomized controlled trial conducted between February 2019 ‐ June 2021. Participants (N = 260 familial caregivers for people with dementia or mild cognitive impairment living in the US) completed a baseline survey at the start of the study and follow‐up surveys every three months for six‐nine months. Questionnaires included the Zarit Burden Index, the Beck Anxiety Inventory, and the Center for Epidemiological Studies Depression scale. We determined the date of lockdown based on the first lockdown order issued in the participant’s state of residence. For each survey score, we also determined the number of days before or after the lockdown date.

Result

The mean age of caregivers in the sample was 63.93 years and 68% were female. A regression predicting caregiver burden from the days before/after lockdown revealed that burden decreased over time, (β = ‐0.008, p = .051). Consistent with this, comparing the average of all scores obtained after lockdown with those obtained before lockdown indicated that burden decreased during lockdown, (t(172) = ‐2.52, p = .013). Levels of caregiver anxiety and depression were not associated with days before/after lockdown and did not change from before lockdown to after lockdown (p’s >.05).

Conclusion

Surprisingly, caregivers in our sample experienced a decrease in burden associated with COVID lockdown. We believe this may result from lockdown providing relief from caregivers’ other responsibilities (e.g., being able to work from home, reduced social obligations). The lack of changes in anxiety and depression may reflect this as well, with these areas of relief offsetting some of the stresses that would normally result in worsening mood for caregivers. In future research we hope to further explore these complex relationships among lockdown, burden, depression, and anxiety.
A molecular approach in DRUG DEVELOPMENT for the management of cognitive dysfunction in Alzheimer’s Disease.
Authors: Silakari Pragati , Piplani Poonam
Published: December 2022

Background

Cognitive decline is budding as one of the greatest health threats in the current scenario as it results in conditions like impaired attention, learning, memory, and problem solving incapability in the patient of Alzheimer’s disease. Neuroinflammation, neurodegradation and oxidative stress can lead to cognitive decline and neuronal loss. Currently, only four AChE inhibitors (tacrine, rivastigmine, donepezil and galantamine) have been approved by the FDA for the symptomatic treatment of AD. However, these acetylcholinesterase inhibitors are not devoid of side effects and have lesser CNS permeability. This instigated further development in the fields of AChEIs and antioxidants for cognitive decline as investigations in these fields seems promising and encouraging. A series of novel polyamino‐substituted‐1,4‐benzoquinone molecules were designed and synthesized against the target AChE and evaluated for their in vitro, in vivo, and ex vivo AChE inhibitory activity and antioxidant potential for the development of novel potent molecules for the management of cognitive decline.

Method

Series of novel amino‐substituted‐1,4‐benzoquinone derivatives have been designed and docked with the binding pocket of the enzyme AChE. These molecules were synthesized and evaluated for their selective in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential, and for antioxidant potential using DPPH and hydrogen peroxide radical scavenging protocols. Further these compounds have been evaluated against behavioral alterations using step down passive avoidance and escape learning protocol with reference to the standard donepezil. Subsequently, compounds were further subjected for their ex vivo AChE inhibition using mice brain homogenate as the source of enzyme. Biochemical estimation of markers of oxidative stress (lipid peroxidation, superoxide dismutase, glutathione and catalase) has also been carried out to determine the role of the synthesized molecules on the scopolamine induced oxidative damage.

Result

Our outcomes depicted that the anti‐amnesic effect of the synthesized conjugates on scopolamine‐induced memory impairment may be related to the mediation of cholinergic system and their effective antioxidant activity.

Conclusion

The results obtained from pharmacological studies were found to be appreciable and provided promising leads which can be further explored structurally and pharmacologically, presenting a favorable scenario for the development of selective AChE inhibitors for the management of cognitive decline.
Evidence of hospital‐based HIT infrastructure and reduced Medicare payment and racial and ethnic disparities among ADRD patients
Authors: Chen Jie , Spencer Merianne , Buchongo Portia , Wang Minqi
Published: December 2022

Background

Understanding the potential cost‐saving or cost‐enhancing of HIT adoptions can help policymakers understand the capacity of HIT investment for population health and racial and ethnic groups. The objective of the study is to examine access to the hospital‐based HIT infrastructure and its association with Medicare payments by Alzheimer’s disease and related dementia (ADRD) patients’ racial and ethnic groups. ADRD is one of the most expensive health conditions in the Unites States and substantial racial and ethnic disparities are observed.

Method

We used 2017 Medicare Beneficiary Summary File, inpatient claims, and the American Hospital Annual survey. Generalized linear models were used for the payment regressions.

Results

The adjusted total Medicare payment and acute inpatient Medicare payment per person per year were higher for ADRD beneficiaries treated in hospitals with telehealth‐post discharge functions (e.g., an incremental increase of $542 in total payment). However, it relates to a significant reduction of Medicare payments to Black ADRD patients (approximately a reduction of $1,104). The finding suggested that telehealth‐post discharge might be cost‐enhancing at the population level; however it is cost‐saving to Black patients with ADRD. The cost‐saving of Black patients exceeded the incremental cost of the adoption of HIT‐post discharge. Similar findings were found for the telehealth‐treatment, which was associated with a significant reduction of payments among Black and Hispanic ADRD patients.

Conclusions

Results suggested that personalized HIT utilization and provisions (telehealth‐post‐discharge for Black and telehealth‐treatment for Black and Hispanic ADRD patients) are critical components of receiving high‐quality ADRD treatment for minority patients.
APOE4 mice rely more on the plasma DHA than APOE3 mice, especially in glia morphology and cognitive performance.
Authors: Plourde Melanie
Published: December 2022

Background

The metabolism of docosahexaenoic acid (DHA), an omega‐3 fatty acid, is different in APOE4 carriers. Brain relies on the plasma DHA pool for its need but the plasma‐liver‐brain axis in relation to cognition remains obscure. We hypothesized that this relation is compromised in APOE4 mice considering the differences in fatty acid metabolism between APOE3 and APOE4 mice.

Method

Male and female APOE3 and APOE4 mice were fed either a diet enriched with DHA (0.7 g DHA/100 g diet) or a control diet for 8 months. Barnes maze and object recognition tests were performed in mice. Immunofluorescence was eprformed on parafin embeded brain slides with GFAP and IBA‐1 and multiplex cytokines were measured in hippocampus protein extracts.

Result

In the cortex, a genotype effect was found where APOE4 mice had higher concentration of DHA than APOE3 mice fed the control diet. APOE4 mice had 20‐30% lower plasma DHA and arachidonic acid (AA) concentrations, adipose tissue AA concentrations than APOE3 mice, independent of diet. In APOE4 mice, there was a significant correlation between plasma DHA and scores on the Barnes maze and with better recognition index. In addition, APOE4 mice fed the DHA diet had lower hippocampal concentrations of interleukin‐7, lipopolysaccharide‐induced CXC chemokine and monocyte chemoattractant protein 1, and higher concentration of interferon‐gamma compared to APOE4 mice fed the control diet. We also found that a diet rich in DHA enhances reactive astrogliosis and ramified microglia morphology in APOE4 mice.

Conclusion

Altogether, our data support that APOE4 mice rely more on the plasma DHA than APOE3 mice, especially in cognitive performance and astrocytes and microglia morphology. Any disturbance in plasma DHA metabolism might have a greater impact on cognition in APOE4 carriers.
Lymphatic drainage at the meningeal‐brain interface in aging and Alzheimer’s disease
Authors: Da Mesquita Sandro
Published: December 2022

Background

Alzheimer’s disease (AD) is the most prevalent form of dementia. We have recently shown that proper meningeal lymphatic drainage is important for brain fluid flow, learning and memory in aging and for brain amyloid beta (Aβ) clearance in mouse models of AD. Interestingly, genetic factors that increased the risk for AD are also linked to altered meningeal lymphatic function.

Method

Meningeal lymphatic function was evaluated in mouse models of AD at different ages by RNA sequencing of sorted meningeal lymphatic endothelial cells (LECs) and by assessing of lymphatic vessel morphology and drainage capacity. Meningeal lymphatic dysfunction was induced by photoablation, whereas enhancement of meningeal lymphatic drainage was achieved by increasing the levels of VEGF‐C. The transcriptional signatures of brain blood endothelial cells and microglia were determined by single‐cell RNA sequencing upon manipulation of meningeal lymphatic drainage. Changes in Aβ plaque clearance by monoclonal antibodies were assessed upon prolonged manipulation of meningeal lymphatic drainage. Integrated analysis was performed using murine and human cell RNA‐seq data, as well as AD summary statistics.

Result

We show that a progressive deposition of meningeal Aβ with aging leads to gene expression changes in meningeal lymphatic endothelial cells and an accelerated reduction in meningeal lymphatic vessel coverage in the 5xFAD mouse model. Interestingly, modulating meningeal lymphatic function in AD transgenic mice affects the clearance of Aβ by monoclonal antibodies, a feature that is closely associated with the activation signatures in brain blood endothelial cells and microglia. Furthermore, genes that are highly expressed in lymphatic vasculature are associated with increased risk for AD and altered levels of Aβ in the CSF of AD patients. Integrated analysis of murine and human microglia transcriptomes revealed an association between the signatures of activated microglia from mice with defective meningeal lymphatic function and activated microglia isolated from the AD brain. We are now turning our attention to the interaction between the main genetic risk factor for AD, expression of the apolipoprotein E4, and changes in brain drainage by the meningeal lymphatic vascular system.

Conclusion

Collectively, our data underline the notion that a dysfunctional meningeal lymphatic vasculature may impact on AD pathophysiology and therapeutic outcome.
Impacts of Aerobic Capacity, Liver Function, and Metabolism on Brain Health
Authors: Lysaker Colton R , Troutwine Benjamin R , Strope Taylor A. , Franczak Edziu M , Allen Julie A , Chauhan Munish , Harris Janna L , Thyfault John P , Wilkins Heather M
Published: December 2022

Background

Aerobic capacity (VO2 max) strongly influences biological functions including both liver and brain function. Low aerobic capacity has far reaching impacts with both increased risk of non‐alcoholic fatty liver disease (NAFLD) and Alzheimer’s disease (AD). Previous work has shown that poor liver function was associated with decreased cognitive function and increased risk of AD. In addition, diet and lipid metabolism play a critical role in brain health, however, the full relationship between these factors and AD risk needs to be elucidated.

Method

We assessed brain mitochondrial function and AD pathology in rats selectively bred for aerobic capacity (low‐capacity runners or high capacity runners, bred over 43 generations). Mitochondrial function was assessed using Seahorse XF technology and spectrophotometric Vmax assays. Phosphorylated tau and Aβ levels were analyzed using western blotting and ELISAs. We assessed outcomes at 12, 18, 24, and 28 months. A separate cohort of rats were fed a low‐fat diet (LFD), high fat diet (HFD), or high fat diet with bile acid sequestrant (HFD+BA) and followed from age 6 to 12 months. Barnes and Y‐maze were performed to measure cognitive outcomes. MRI/MRS was completed to measure hippocampal volume and neurochemical profiles.

Result

Mitochondrial function parameters were different between groups and with different diets in both brain and liver. Overall LCR animals had reduced brain mitochondrial function and reduced resilience with long term HFD. LCR rats had increased phosphorylated tau levels. Female rats with a low intrinsic aerobic capacity (LCR) have significantly higher levels of Aβ42 when compared to rats with a high intrinsic aerobic capacity (HCR). LCR rats performed worse on the Y‐maze beginning at 10 months of age irrespective of diet.

Conclusion

Aerobic capacity and diet affect brain health during aging. Liver function appears to play a large role in brain health outcomes. We continue to analyze MRI/MRS and cognitive data in correlation with liver function.
Donepezil prevents cognitive impairment and gut epithelial disruption in doxorubicin‐treated rats
Authors: Suparan Kanokphong , Ongnok Benjamin , Khuanjing Thawatchai , Thonusin Chanisa , Chattipakorn Nipon , Chattipakorn Siriporn C
Published: December 2022

Background

Donepezil (DPZ) is an acetylcholinesterase inhibitor used to improve cognitive function. We reported that it prevented doxorubicin (Dox)‐induced chemobrain. Gut epithelial disruption, gut dysbiosis and impaired essential microbial metabolites, such as short chain fatty acids (SCFAs), have found following Dox therapy. However, the impact of DPZ to prevent gut epithelial disruption and gut dysbiosis as well as disturbance of circulating SCFAs due to Dox‐induced chemobrain have been never investigated.

Method

Twenty‐four rats were divided into sham rats, vehicle‐treated Dox rats, and DPZ‐treated Dox rats. Modified Novel Object Location and Recognition tests were used to evaluate cognitive function. At the end of the study, ileums were removed to investigate occludin protein expression, and PCR of ileal luminal contents were used to calculate Firmicutes to Bacteroidetes (F/B) ratio. Serum butyric acid, a representative of SCFAs, was assessed by Gas chromatography‐mass spectrometry.

Result

Dox‐rats developed cognitive impairment with gut epithelial disruption, gut dysbiosis and reduced essential microbial metabolites (serum butyric acid). DPZ significantly prevented cognitive decline in Dox‐rats (Fig 1A‐C). Furthermore, DPZ restored the expression of occludin in gut tissue, suggesting that DZP improved gut epithelial integrity in Dox‐rats (Fig 1D). DZP improved gut dysbiosis in Dox‐rats as indicated by attenuated F/B ratio (Fig 1E), but level of serum butyric acid between DZP‐treated Dox rats and vehicle‐treated Dox rats was not different (Fig 1F).

Conclusion

DPZ co‐treatment with Dox prevented Dox‐induced cognitive impairment. Although DZP protected gut epithelial disruption, and improved gut dysbiosis, however it could not help to increase circulating SCFAs. These findings suggest that DPZ, itself, cannot completely prevent the gut disturbance in rats with Dox‐induced chemobrain. Therefore, the probiotic supplement with DZP might be the other approach to prevent gut problem following chemotherapy.
Efficacy and Safety of Adding Kami Guibi‐tang to Acetylcholinesterase Inhibitor for Cognitive Function in Mild Alzheimer’s Disease: A Pilot, Randomized, Double‐blind, Placebo‐controlled Trial
Authors: Yim Tae‐Bin , Kim Ha‐Ri , Shin Hee‐Yeon , Heo Hye‐Min , Jahng Geon‐Ho , Cho Seung‐Yeon , Park Seong‐Uk , Ko Chang‐Nam , Park Jung‐Mi
Published: December 2022

Background

The main treatments for mild AD have been acetylcholinesterase inhibitors(AChEI). However, no current drugs can fundamentally treat AD or reverse advanced cognitive decline. This clinical study was conducted to explore the efficacy and safety of adding Kami Guibi‐tang(KGT) to AChEI for cognitive function in elderly patients with mild AD.

Method

This study was designed as the pilot for a larger randomized, double‐blind, placebo‐controlled study. Elderly participants aged 55 to 90 years diagnosed with mild AD. Subjects were randomized to receive either KGT or placebo for 24 weeks, in addition to their regular AChEI. The primary study outcome was treatment efficacy as assessed by the relative amount of change over the study period in total scores on the Dementia version of the Seoul Neuropsychologic Screening Battery(SNSB‐D). Changes in SNSB sub‐scores such as the Korean Mini‐Mental State Exam(K‐MMSE) and in scores on the Korean version of Quality of Life‐Alzheimer’s Disease(KQoL‐AD), and the Caregiver‐Administered Neuropsychiatric Inventory(CGA‐NPI) were assessed as secondary outcomes. We also monitored patient safety parameters including adverse events and abnormalities in blood tests, electrocardiogram, and brain magnetic resonance imaging tests.

Result

7 participants in the KGT group and 7 participants in the placebo group completed the 24‐week trial. There were no significant changes in SNSB‐D total/subindex scores, KQoL‐AD or CGA‐NPI scores for either group, and no significant differences were observed between the two groups. K‐MMSE scores were decreased significantly within each group, but were not significantly different between groups. No adverse events related to KGT were reported. In addition, we compared / analyzed the results of a previous pilot study conducted on amnestic mild cognitive impairment(aMCI) with the same protocol as this study. The aMCI group showed a significant improvement in the total SNSB‐D score(especially in the memory domain) and K‐MMSE and Korean Instrumental Activities of Daily Living scores compared with the mild AD group.

Conclusion

Adding KGT to AChEI did not significantly improve cognitive function in SNSB compared to placebo. Although KGT did not show cognitive improvement in the patients with mild AD in this study, we suggest that KGT would have a positive effect on the patients with early stages of cognitive impairment such as aMCI.
Is the U.S. clinical trial infrastructure optimized to meet the current and growing enrollment needs?
Authors: Scholler Emily , Beck Erin , Eimerbrink Micah
Published: December 2022

Background

Alzheimer’s disease (AD) clinical development continues to expand with 28 drugs in Phase 3, 74 in Phase 2, and 24 in Phase 1 in 2021. This study seeks to investigate how the U.S. clinical trial infrastructure is prepared to meet the current and growing enrollment needs. We aim to evaluate the overlap between regional density of persons with dementia (PWD) and trial site service areas with attention to how coverage gaps impact the ability to enroll study participants representative of the national population diagnosed with AD.

Method

Prevalence of AD by race, gender, socioeconomic status and language was collected using the 2019 US Census Bureau. Data on trial site location was gathered using ClinicalTrials.gov and a third party service. The SiteRx Provider Network, a network of over 1,200 treating neurologists and primary care physicians that refer patients to research across 28 US states, was gathered using ZIP codes from a proprietary database. AD prevalence by ZIP code was compared against ZIP codes of current clinical trials sites that conduct Phase 1‐3 CNS trials across the U.S and SiteRx Provider Network using a radius of approximately 60 miles.

Result

There are gaps between PWD and trial sites locations, which are significantly worse for minority patients. Heat maps were created using Excel and Tableau to visualize data, which indicated key areas of infrastructure misalignment given existing patient populations. Additional analysis was performed to explore how PWD and site location incompatibility impacted potential enrollment based on key demographic domains.

Conclusion

The current AD clinical trial site infrastructure is not well equipped to meet the growing need for clinical trial recruitment. SiteRx is positioned to strengthen trial infrastructure through their ability to bridge community‐based care with nearby research sites to optimize enrollment at current sites and identity geographies in need of trial sites given the existing AD patient population.
Higher CSF Ab38 levels protect against cognitive decline in high‐functioning individuals
Authors: Bruno Davide , Reichert Chelsea , Zetterberg Henrik , Blennow Kaj , Pomara Nunzio
Published: December 2022

Background

The amyloid cascade hypothesis proposes that Alzheimer’s disease (AD) pathology starts with accumulation of b‐amyloid (Ab) peptides, leading to plaque deposition. In this context, the spotlight has been pointed firmly onto Ab42, but evidence suggests that shorter isoforms may also play an important role in modulating AD pathophysiology. A recent report with individuals with mild cognitive impairment or subjective cognitive decline (Cullen et al., 2021) has shown that higher cerebrospinal fluid (CSF) levels of Ab38 were associated with less decline on the mini‐mental state exam (MMSE) score and reduced risk of conversion to AD. The aim of this study was to test whether CSF Ab38 levels also predicted change in MMSE scores in cognitively intact individuals.

Method

Data were obtained from 40 individuals (age = 67.3, 6.3), who had taken part in a study on late‐life major depressive disorder at the Nathan Kline Institute and New York University. Data were available for baseline examination as well as three‐year follow up. Twenty‐three individuals were depressed at baseline, and 17 were controls; all had an MMSE score of 28 or higher at baseline. To test our hypothesis, we carried out a Bayesian linear regression analysis with change in MMSE score from baseline to follow‐up as outcome; CSF Ab38, CSF Ab42, and CSF phosphorylated (p) tau as predictors; and controlling for age, sex, APOE e4‐status and depression diagnosis (null model).

Result

The results showed that the model combining CSF Ab38 and CSF p tau was the strongest, with moderate evidence (BFm = 4), carrying nearly double the odds of the model with all predictors (BF10 = 0.539), and 4.6 times the odds of the null model (BF10 = 0.219): higher baseline levels of CSF Ab38 were associated with less decline in MMSE score, while higher p tau levels were linked to more decline. When isolating depressed individuals, the pattern of results was unchanged, while the null model was strongest with controls.

Conclusion

These findings confirm the importance of examining shorter Ab isoforms also in individuals with no cognitive impairment or subjective cognitive decline.
Projected costs of dementia and quality adjusted life years lost between 2020‐2050: a population‐based microsimulation study
Authors: Brück Chiara C.
Published: December 2022

Background

The total cost of dementia has passed the $1 trillion mark in 2018 and dementia was the sixth most burdensome disease in 2016, causing an immense loss of quality adjusted life years (QALYs). Due to population ageing, costs and burden will further increase. We have quantified the expected future increase in costs and QALYs lost due to dementia.

Method

We used the microsimulation model MISCAN‐Dementia to simulate the life history and development of dementia of 10 million individuals. MISCAN‐Dementia synthesizes population‐based Rotterdam Study data with changes in demographics between birth cohorts from the early 1900s onwards. We assumed cost (from a societal perspective) and disutility values for patients and caregivers by dementia severity stage (MCI, mild, moderate, severe) and setting (home, institution). We determined costs and QALYs lost from 2020‐2050 for three different dementia risk trend scenarios: 1) stable age‐specific incidence, 2) linear decline by 13% per decade, 3) nonlinear declines averaging 13% per decade.

Result

We estimated total costs of dementia in 2020 at 13 billion euros and QALYs lost at 90,000 years for the general Dutch population, irrespective of the trend scenario. Assuming a stable age‐specific incidence resulted in costs of 29 billion euros and 207,000 QALYs lost in the year 2050, corresponding to a 124% increase compared to 2020. In contrast, the linearly declining trend resulted in 19 billion euros (95%CI: 15‐24) and 135,000 QALYs lost (95%CI: 106,000‐169,000) in 2050, translating into a 53% increase compared to 2020. Over the time horizon, costs and QALYs lost are roughly similar between dementia stages, although people spend more time with less severe disease (50% mild, 30% moderate, and 20% severe dementia). Similarly, costs of institutionalized care (30% of life years spent with dementia) are roughly equal to the costs while living at home (70% of life years spent with dementia).

Conclusion

By 2050, the annual costs of dementia will increase to 19‐29 billion euros and dementia will cause 135,000‐207,000 QALYs lost per year. These projections highlight the need for policymakers and health care systems to prepare for an increase in the burden of dementia.
Subjective Cognitive Decline symptom burden is associated with self‐perceived risk for AD
Authors: Jacova Claudia , Robertson Frank , Smith Samantha
Published: December 2022

Background

Subjective Cognitive Decline (SCD) refers to a self‐experienced decline in cognitive capacity despite normal performance on objective tests. Research has consistently linked SCD to incident Alzheimer’s disease (AD). The role of perceptions around aging and AD risk in the SCD experience has not been clearly delineated. Here we aimed to determine the association between chronological age, self‐perceived risk for AD, and SCD symptom burden.

Method

Community‐dwelling participants aged ≥50 years (n = 483), located within the United States were recruited via the crowdsourcing website Amazon Mechanical Turk. They completed a survey consisting of demographic questions and the Subjective Cognitive Decline Questionnaire (SCD‐Q MyCog). The survey also included items about self‐perceived risk for AD (“Do you believe that you are at higher risk of AD than your peers”; endorsed = 1, not endorsed = 0) and an AD family history (endorsed = 1; not endorsed = 0). Linear regression was used to predict SCD total score from combinations of these measures, adjusted for gender.

Result

The sample’s descriptive data were: age M = 64±5.5, range 50–79, SCD total M = 4.7±5.8, range 0–24, 66.5% female. There were 17% (n = 82) who perceived themselves at heightened risk for AD, and 27% (n = 132) with a positive family history. When entered together, high perceived risk predicted higher SCD total whereas family history and age were not predictive: B = 4.9, p<.001, B = ‐.004, p = .99, B = ‐.024, p = .59, respectively, R‐squared = .11. SCD total was M = 8.8±6.6 for the high‐risk, 3.9±5.2 for low‐risk group. Adding age squared did not improve the model: B = ‐.001, p = .88. Interaction analyses revealed a trend for perceived AD risk but not family history to be conditional on age, B = ‐.260, p = .067, B = .060, p = .603..Johnson‐Neyman regions‐of‐significance indicated that beyond age 70, the coefficient for self‐perceived AD risk approached zero and was non‐significant:

Conclusion

Our findings highlight the importance of self‐perceptions of AD risk for SCD in the youngest old adults (age<70). These individuals appear to evaluate their cognitive capacity in relation to their perceived susceptibility to AD. Interestingly, objective risk (older age, AD family history) does not contribute to this evaluation.
Higher Dietary Inflammatory Index scores are not associated with cognitive decline in the Framingham Heart Study
Authors: van Lent Debora Melo , Gokingco Hannah , Beiser Alexa S , Yuan Changzheng , Jacques Paul F , Vasan Ramachandran S , Seshadri Sudha , Jacob Mini Elizabeth , Himali Jayandra J
Published: December 2022

Background

Nutritional factors can abet or protect against systemic chronic inflammation, which plays an important role in the development and progression of dementia. We evaluated whether higher (i.e. pro‐inflammatory) Dietary Inflammatory Index(DII) scores were associated with accelerated cognitive decline in the community‐based Offspring Framingham Heart Study(FHS).

Method

889 older adults (mean age 59 years [standard deviation (SD)], 8;58.3% women]) completed validated 126‐item Food Frequency Questionnaires(FFQ), administered at FHS examination cycle 7 (1998‐2001) and examination cycle 5 (1991‐1995) and/or 6 (1995‐1998). We created a DII score (based on the published method by Shivappa et al. 2014); a cumulative DII score was calculated by averaging across a maximum of three FFQs. Cognitive testing was completed at examination cycles 7, 8 (2005‐2008) and 9 (2011‐2014). Exam 7 was considered as study baseline and participants were followed over a mean time of 13.4 years (SD 1.3). We excluded participants with prevalent dementia or stroke at baseline and those with no cognitive testing follow‐up data. We examined associations between the cumulative DII score and cognitive test scores over time using linear mixed models adjusting for age, age‐squared, sex, education, time from exam 7 to neuropsychological exam 7, and time (model1) and additionally for apolipoprotein e4, body mass index, total energy intake, total cholesterol: high‐density lipoprotein ratio, physical activity, smoking and anti‐cholesterol medication (model2).

Result

Higher DII scores were significantly associated with accelerated decline in performance on the Trail Making Test B minus A(TMT‐B minus A) (processing speed and executive function), following adjustment for model 1 covariates (β±SE, ‐0.001± 0.0004,p = 0.03). but the association failed to reach significance in Model 2 (‐0.001±0.0003,p = 0.08). We observed no relationship between higher DII scores and other cognitive domains. Stratified analyses showed that higher DII scores were associated with accelerated decline in TMT‐B minus A scores among apolipoprotein e4 carriers (Model 2:‐0.002±0.001,p = 0.047) but not among non‐carriers (Model 2:‐0.0004±0.0004,p = 0.33).

Conclusion

Higher DII scores were not associated with cognitive decline. To date, such studies have been very limited, most studies that found a relationship, were cross‐sectional and have used less sensitive testing. Future studies are encouraged to examine whether our findings can be replicated.
A brain atlas of astrocyte transcriptomics unveils complex states and responses to Alzheimer’s disease neuropathology
Authors: Serrano‐Pozo Alberto , Li Zhaozhi , Woodbury Maya E. , Wachter Astrid , Bryant Annie G , Noori Ayush , Welikovitch Lindsay A. , Jackson Rosemary J , Lin Gen , Kwon Taekyung , Bennett Rachel E , Talanian Robert V. , Biber Knut , Karran Eric H , Hyman Bradley T. , Das Sudeshna
Published: December 2022

Background

Amyloid‐β plaques and neurofibrillary tangles in the Alzheimer’s disease (AD) brain are accompanied by prominent morphological and functional changes in astrocytes, collectively termed reactive astrogliosis. Single‐nuclei RNA‐sequencing (snRNA‐seq) has begun to unveil the molecular underpinnings of AD reactive astrocytes but technical challenges, including low numbers of nuclei and/or sequencing depth, and the lack of comparisons across brain regions have limited the full picture. Here we present the largest snRNA‐seq study of astrocytes to date across five brain regions.

Method

Nuclei were isolated from five brain areas of n = 32 donors with increasing AD neuropathology (total n = 160 samples). The five brain areas were chosen based on their hierarchical accumulation of tau pathology: entorhinal cortex (EC)> inferior temporal gyrus (BA20) > dorsolateral prefrontal cortex (BA46) > secondary visual cortex (V2 or BA18/19) > primary visual cortex (V1 or BA17). To enrich in astrocytic nuclei, NEUN+ and OLIG2+ nuclei were separated via FACS, whereas NEUN‐/OLIG2‐ nuclei (including astrocytes) were subjected to snRNA‐seq resulting in a transcriptomic dataset of 629,755 astrocyte nuclei, which were subsequently examined for common and region‐specific AD related changes.

Result

Clustering within each brain region identified likely homeostatic and reactive subclusters, as well as six other clusters which we describe as “intermediate” subclusters. Homeostatic and reactive astrocytes were most abundant in V1 (59%) and EC (21%), respectively, and their transcriptomic profiles were anticorrelated. Reactive astrocytes were enriched in cytoskeleton (GFAP MAP2, MAP7, MAPB1, MAPT), extracellular matrix (CD44, LAMA1, TNC, VCAN), chaperones (CRYAB, HSPB1, HSPB8), and oxidative stress/antioxidant (MAOB, MT1X, MT2A, SOD2) genes, whereas homeostatic subclusters in trophic factor (EGFR, PTN) and glutamate metabolism (GLUL, GRIA2, GRM3, SLC1A2) genes. The proportion of intermediate astrocyte subclusters was lowest in EC (25%) and highest in BA46 (41%), and their transcriptome correlated weakly with that of homeostatic and reactive astrocytes, representing an apparent gradient between homeostatic and reactive. Notably, these intermediate subclusters demonstrated the most heterogeneity among brain regions.

Conclusion

Our astrocyte snRNA‐seq dataset encompassing five regions of control and AD brains revealed homeostatic, reactive, and previously uncharacterized intermediate astrocytic states with distinct transcriptomic profiles for each brain region, suggesting complex, region‐specific responses to AD pathology.
Racial disparities in Alzheimer’s Disease (AD): Correlating a novel neuropsychological screening test to established AD fluid and imaging biomarkers in African Americans and Caucasians
Authors: Liu Andy , Rose Deborah K
Published: December 2022

Background

The Montreal Cognitive Assessment (MoCA) is a commonly used screening tool for the diagnosis of neurocognitive disorders such as mild cognitive impairment (MCI) and Alzheimer’s Disease (AD). The current cut‐off threshold for detection of MCI on the MoCA increases risk for false positives, particularly in ethnic minorities and those of lower educational attainment. African Americans (AA) have experienced inaccurate detection of MCI and AD, leading to a delay in diagnosis and a decreased enrollment in AD‐related clinical trials. This underscores the importance of clarified cut‐offs for AD plasma biomarkers in AA and a standardized cognitive screening test independent of language and cultural norms. The Visual‐based Cognitive Assessment Test (VCAT) is a newly developed language‐neutral cognitive screening test that has good sensitivity (85.6%) and specificity (81.1%) in diagnosing MCI and mild AD. Our study will correlate VCAT scores to MRI brain findings and established AD plasma biomarkers in AA and Caucasians with and without cardiovascular diseases (i.e. prior myocardial infarction, stroke, and chronic kidney disease).

Methods

AA and Caucasians diagnosed with MCI, AD, and normal cognition have been recruited (n=50) over a period of one year (recruitment remains ongoing). Plasma samples were collected, MRI brain imaging and Neuroquant data were obtained (for volumetric analyses), and the VCAT along with the MoCA were completed. Phosphorylated‐tau 181 (p‐tau 181) and phosphorylated‐tau 217 (p‐tau 217) will be measured in the samples using the Quanterix HDX device.

Results

Preliminary results reveal that levels of p‐tau 181 are elevated (from a normative cut‐off value of 1.81 pg/mL per the Youden index) in all groups, and highest in the group of patients with both CSF findings consistent with AD and a medical history of cardiovascular diseases (MI, CKD, and/or stroke).

Conclusion

Established cut‐off values for p‐tau 181 and p‐tau 217 in the literature likely underestimate these results in AA patients. In addition to elucidating the cut‐off normative values for established plasma AD biomarkers in a diverse cohort, our goal is to validate the VCAT, a cultural and language‐neutral screening assessment. This will allow for application to multilingual populations without the need for translation of its test contents.
Predicting Alzheimer’s disease progression in healthy and MCI subjects using multi‐modal deep learning approach
Authors: Mirabnahrazam Ghazal , Ma Da , Beaulac Cédric , Lee Sieun , Popuri Karteek , Lee Hyunwoo , Cao Jiguo , Wang Lei , Galvin James E , Beg Mirza Faisal
Published: December 2022

Background

Alzheimer's disease (AD) is a complex disorder influenced by many factors, but it is unclear how each factor contributes to disease progression. An in‐depth examination of these factors may yield an accurate estimate of time‐to‐conversion to AD for patients at various disease stages. Recent advances in deep learning have enabled researchers to predict patient’s disease onset time by exploring the influencing factors in AD progression.

Method

We used 543 subjects with 63 features from 3 data modalities from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The following modalities were used: 1) MRI, 2) genetic and 3) DTC (Demographic, cognitive Tests and Cerebrospinal fluid). The 21 most important features were automatically selected for the three modalities.

We used a Deep Learning‐based survival analysis model that extends the classic Cox regression model to predict the subjects' disease onset time. Here we re‐define the non‐AD‐progression as “survivor”, and AD‐progression as “non‐survivor”. The subjects were divided into two groups: progressive subjects (non‐survivor), who were either healthy or diagnosed with Mild Cognitive Impairment (MCI) at initial clinical visit and later developed AD, and non‐progressive subjects ("survivor”), who were either healthy or MCI at initial visit but did not develop AD later. We used 10 random sub‐samples, selecting 80% of the subjects for training and 20% for testing each time; 20% of training data was used for internal validation.

Result

Figure 1 shows the estimated survival rates over 10 years. Both groups had a high survival chance at the start. The progressive group's survival chance dropped much faster and fell below 20% by the end of the period. The non‐progressive group's survival chance remained around 50%.

Feature importance analysis is displayed in Figure 2. Eight of the top ten most important features are from the cognitive tests, demonstrating their importance in survival analysis. Amygdala and Hippocampus regions, as well as age, are also notable features.

Conclusion

Our study demonstrated that using powerful predictive models on multi‐modal data can improve prediction of time‐to‐conversion. This not only leads to a better understanding of AD, but also provides essential tools for practitioners who wish to follow their patients' disease progression.
Professor of computer science weighs in on robots in nursing homes
Authors: Khan Arshia A
Published: December 2022

Background

Staff shortages are a major concern in nursing homes. The residents are experiencing reduced care. Care is suffering and actions are needed to address the shortage of staff.

Method

Humanoid robots can be employed to address the shortages in staff. These robots can be performing tasks that are repetitive and can release the staff to perform other important tasks

Result

Humanoid robots can improve the care provision to the elderly and people affected with dementia.

Conclusion

Consider employing robots in nursing homes to improve quality of care in nursing homes.
Age Friendly Emergency Medicine Services: Integrating What Matters, Medications, Mobility, and Mentation into Emergency Response
Authors: Taylor Kate , Wagner Teresa
Published: December 2022

Background

Our population is aging. The Age Friendly Health System (AFHS) initiative by the Institute of Healthcare Improvement (IHI) includes the 4 M’s of What Matters, Medications, Mobility, and Mentation, and is at the forefront of older adult health care. When applying the 4M’s to emergency medical services (EMS), the benefits include avoiding unnecessary transports and helping the patient stay healthy and safe in their home setting. The University of North Texas Health Science Center and other partnerships aspired to designate MedStar the first AFHS in the country within EMS practice.

Method

The Plan‐Do‐Study‐Act (PDSA) cycle aimed at various changes with the AFHS components of What Matters and Medications within an electronic medical record (EMR) algorithm for emergency medical paramedics. Additionally, previously piloted geriatric practice leadership institute projects embedded Mentation and Mobility by including specific screenings in the EMR.

Result

The preliminary result in the PDSA described showed 52% of older adults answered health when asked What Matters most to them today. However, updated data as of January 2022, showed an overwhelming 6732 (69%) patients out of 9685 patients, answered health when asked What Matters most to them today. Additionally, the EMR identifies high‐risk medications. Paramedics can now verify potential risks and develop a care plan based on the identified high‐risk medications.

Conclusion

Implementing AFHS components allows for better care delivery and outcomes as our older population is growing and embraces more complexities. The data is still novel but promising, requiring longitudinal information before conclusions can be considered.

IHI is currently reviewing opportunities to expand its models of care into emergency medicine, behavioral health, and other settings. MedStar sets the example that EMS can practice the AHFS approach serving as a model for the EMS environment. We are currently awaiting feedback from IHI regarding our request to designate MedStar the first AFHS EMS practice in the country.
Physical Activity Trajectories, Autonomic Balance and Cognitive Function: the CARDIA Study
Authors: Gafni Tal , Gabriel Kelley Pettee , Shuval Kerem , Yaffe Kristine , Sidney Stephen , Weinstein Galit
Published: December 2022

Background

Physical activity (PA), and particularly moderate to vigorous intensity PA (MVPA), may protect against cognitive decline. However, the underlying mechanisms are not fully understood. Cardiac autonomic balance is influenced by PA and implicated in dementia pathogenesis. Therefore, the study aimed to examine whether autonomic balance mediates the association between PA and cognitive function.

Method

The sample included 1,939 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study. MVPA was obtained in 7 consecutive examinations from baseline (1985‐86; 18‐30 years) to the Year 20 exam. Cardiac autonomic balance was assessed at Year 20 via resting heart rate, and via measures of heart rate variability: standard deviation normal to normal (SDNN) and root mean square of successive differences (RMSDD). A comprehensive cognitive assessment was performed at Year 30. Group‐based trajectory modeling was used to identify homogenous MVPA trajectory groups, and formal mediation analysis was used to test whether cardiac autonomic function indices lie on the causal pathway between MVPA trajectories and cognitive function.

Result

Three distinct PA trajectory patterns were identified: (1) Below MVPA guidelines (n = 1,122; 57.9%); (2) Meeting MVPA guidelines (n = 652; 33.6%); and (3) Exceeding MVPA guidelines (n = 165; 8.5%) (Figure). Meeting and exceeding MVPA guidelines were related to lower resting heart rate and higher heart rate variability, which indicate improved autonomic balance. Meeting and exceeding MVPA guidelines were additionally associated with improved semantic fluency performance. The association between higher MVPA level and semantic fluency performance was fully mediated by RMSDD and partially mediated by SDNN. No additional associations were observed between MVPA trajectories and other cognitive outcomes, and no statistically significant mediation by autonomic balance indices was found for these associations (Table).

Conclusion

Higher MVPA levels across the young adult to midlife transition were associated with better cardiac autonomic function, which in turn explained some of the associations between PA trajectories and better semantic fluency performance. Future studies, particularly among older individuals are warranted to clarify the role of autonomic balance in the link between physical activity and brain health. These findings may lead to more targeted PA recommendations across the life‐course to slow cognitive decline and decrease dementia risk.
High Social Deprivation as a Risk Factor for Dementia: Findings from the longitudinal SHARE study of older Europeans
Authors: Hofbauer Lena M , Rodriguez Francisca S
Published: December 2022

Background

Individual‐level deprivation indices are only just emerging, but are better indicators than area‐level indices. The Social Deprivation Index (SoDep Index) was developed by our team last year as an indicator of the degree to which an individual experiences socioeconomic deprivation. It has shown a robust association with cognitive status and decline in adults over 50. However, its association with dementia diagnosis is unknown.

Method

We analysed data of > 11, 000 respondents in the Survey of Health, Ageing and Retirement in Europe (SHARE) over the age of 50 who were free of dementia at baseline. Social deprivation status (low, moderate, high) was classified on the basis of SoDep Index scores. The risk of dementia diagnosis was estimated using Cox proportional hazard and Fine and Gray models (correcting for mortality) including social deprivation status and relevant covariates. Further, we completed a sub‐group analysis of individuals with high social deprivation status and analysed the relevance of a history of depression in each deprivation group.

Result

Results show that high, compared to low, social deprivation was associated with a significantly increased risk of being diagnosed with dementia. Both, depressive history and depressive symptoms were additionally associated with an increased risk. The associations between depression indicators and dementia risk were particularly pronounced in the high social deprivation sub‐group. Results were robust to correction for mortality.

Conclusion

Social deprivation status is associated with an increased dementia risk. This adds to a growing body of evidence indicating that a public health approach to dementia prevention must address socioeconomic inequity. Increased risk in population groups with high social deprivation cannot be accounted for by higher rates of depression. Thus, our results lend additional weight to the argument that adults with depression from vulnerable groups need urgent intervention.