bluuebunny/crossref_metadata_2025 huggingface dataset:
The virtual interface for neurodegenerative disease management: A systematic literature review on the feasibility of telemedicine in dementia care
Authors: Gosse Paula , Masellis Mario , Etchells Edward , Mitchell Sara Berman
Published: December 2020

Background

As the global population ages and the prevalence of dementia rises, telemedicine has garnered attention as a means of delivering care to a frail cognitively‐impaired population through a virtual interface. The benefits of telemedicine‐based in person patient‐physician encounters include increased access to healthcare irrespective of distance, as well as reduction in travel costs and carbon emissions. While Telemedicine has proven feasible and effective in other areas of medicine, its use in a cognitively‐impaired population is less well studied and poses unique challenges. The current literature review aims to compare and contrast the use of televisits across neurodegenerative disease, with a particular focus on dementia care.

Method

We performed a systematic review of the literature published between January 2000 and January 2020. Databases OVID Medline and PubMed were searched using keywords “Telemedicine”, “Neurodegenerative disease”, “Dementia” and their respective synonyms. Eligible articles were selected after screening the titles and abstracts. Studies were included if they examined the use of virtual healthcare visits (i.e. televisits) in the management of patients with neurodegenerative diseases.

Result

The search yielded 503 potentially eligible articles. After further screening, a total of 35 articles met inclusion criteria. Positive benefits of televisits across neurodegenerative diseases included high rates of patient satisfaction, feasibility and validity. A particular challenge that emerged as unique in dementia care is a lack of interpersonal engagement.

Conclusion

While telemedicine has clear potential benefits for neurodegenerative disease management, further research is required to assess long‐term clinical and quality of life outcomes in patients with dementia.
Occupational exposure as a risk factor for cognitive impairment in Vietnamese nail salon workers
Authors: Nguyen Thuc‐Nhi , Nguyen Mai Tram , Chen Shuai , Hinton Ladson
Published: December 2020

Background

Nail salon technicians are continuously exposed to neurotoxic and carcinogenic properties in nail products that may put them at risk for central nervous system impairments linked to Alzheimer’s disease. However, there are very few studies of the nail‐care workplace, and even fewer focus on Vietnamese female nail technicians, who make up the overwhelming part of the workforce. This study provides preliminary data on clinical assessments that will inform the cognitive functioning of a vulnerable population.

Method

Sample includes 300 Vietnamese females aged 50 or above in Northern California. The nail‐technician group (n=155) self‐identified as a current or former full or part‐time nail technician. The non‐nail group (n=145) are those who have never worked in the cosmetic industry, including nail or hair salons, but were an approximate match with the nail technicians on demographics and acculturation variables. Participants completed the Montreal Cognitive Assessment (MoCA), the Center for Epidemiologic Studies Depression Scale (CES‐D), and a self‐reported bilingual survey regarding their occupational exposure and demographics.

Result

The average MoCA score was 18.8 (SD ±4.50) for non‐nail technicians, which is significantly higher than 17.60 (SD ±4.30) for nail technicians (p = 0.017). However, there was no significant difference between the two groups on the average CES‐D score (p = 0.22). Based on results of multiple linear regression, with an increase of 100 in exposure index (i.e., years working in current nail salon x hours worked per week), the MoCA score is expected to decrease by 0.29 (95% CI: 0.05, 0.53, p = 0.017).

Conclusion

After adjusting for potential confounders, Vietnamese nail technicians were found to have lower cognitive functioning that those without occupational exposure to nail salon work. The results of this study suggest the need for future longitudinal research to better elucidate the processes underlying this association.
Comparison of digital platforms for participant recruitment in dementia research: Lessons and future directions from a global collaborative
Authors: Jeon Yun‐Hee , Fargo Keith , Smith Adam , Langbaum Jessica B , Nosheny Rachel L , Zwan Marissa D , Shin Mirim , Scheltens Philip , Weiner Michael W , Rossor Martin N
Published: December 2020

Background

Delays in finding the right research participants can result in studies taking longer to deliver, often requiring funding extensions and ultimately limit the effectiveness of research and evaluation when study samples are insufficient for robust analysis and generalisation of findings. Recruitment challenges in dementia research are a global issue.

Method

To improve the effectiveness and efficiency of participant recruitment efforts in dementia research, innovative digital platforms have emerged over the past ten years: TrialMatch, Alzheimer's Prevention Registry & GeneMatch, and Brain Health Registry (USA), Join Dementia Research (UK), Hersenonderzoek (Netherlands), and StepUp for Dementia Research (Australia). Established in 2019, a global collaborative of these platforms aims to generate new insights and evidence that can help further enhance the service provision and potentially support other similar global initiatives. This paper provides an overview and comparison of the platforms, including key successes and challenges in their service delivery.

Result

TrialMatch was the first platform developed to support recruitment processes in 2010. To date, collectively, the seven platforms have over 920,000 volunteer members; >50% of them had opportunities to take part in studies as a result. The services are mostly free and rely on government grants and/or philanthropic funding for their delivery. They share common features (e.g., matching volunteer demographic and clinical information with studies) although some collect and use more detailed genetic and clinical profiles than others. Examination of the matching mechanisms and volunteer data access processes across the platforms suggests various opportunities to enhance the platforms. Key outcomes of these platforms also include a positive change in the way the public perceives dementia research and a systematic way for the public to engage in research. Understanding social and economic impact and ensuring sustainability of the platform and its service delivery are crucial steps for the future.

Conclusion

The seven digital platforms have been showing their power and potential impact not only in fast‐tracking dementia research but also in improving public engagement and participation. Through this global partnership, the members share practices and strategies for sustainability of the programs that can contribute to the development of ‘good’ sustainable models for dementia research recruitment services.
Joint linkage and association mapping of preserved cognition in the old‐order Amish
Authors: Ramos Jairo , Jaworski James , Adams Larry D. , Laux Renee A. , Caywood Laura J. , Prough Michael , Clouse Jason E. , Herington Sharlene D. , Slifer Susan H. , Fuzzell M. Denise , Fuzzell Sarada L. , Sewell Jane L. , Miller Sherri D. , Song Yeunjoo E. , Miskimen Kristy , Main Leighanne R. , Ogrocki Paula , Lerner Alan J. , Vance Jeffery M. , Cuccaro Michael L. , Haines Jonathan L. , Pericak‐Vance Margaret A , Scott William K.
Published: December 2020

Background

Most studies on Alzheimer Disease (AD) have focused on the identification of variants associated with increased risk. The Amish is a genetically homogeneous population ideal to investigate susceptibility genes for complex traits such as AD. This study aims to use family‐based linkage and association approaches to identify genetic variants that protect against the development of cognitive impairment (CI), the central feature of AD.

Method

A total of 800 adults from Amish communities in Indiana and Ohio were screened for CI using the 3MS test. Individuals were classified as cognitively normal (CN) if the 3MS score was ≥87 at age 75 and cognitively impaired if < 87 at any age. Samples were genotyped on the Illumina Infinium Global Screening or Expanded Multi‐Ethnic Genotyping Array. Over 7 Million common and rare variants were then imputed using the HRC reference panel. For the linkage analysis 75 nuclear families containing at least two CN individuals were analyzed using Merlin to fit multipoint non‐parametric linkage models and parametric affected‐only (AO) dominant and recessive models using a map of more than 40,000 genotyped markers. The genome‐wide association study (GWAS) of imputed variants utilized the program Genesis to fit a logistic regression model 426 CN to 360 CI, associating each variant with cognitive status while adjusting for sex, pc1, pc2 and relatedness.

Result

The top linkage peaks were seen in the parametric multipoint AO dominant model: Chr3 (HLOD = 2.6) ∼3.9 mb region (21.0 mb – 24.9 mb) and Chr11 (HLOD 2.1) ∼6.5 mb (11.0 mb – 17.5 mb). In the GWAS analysis, no variants reached genome wide significance (5 × 10−8). However, using a lower significance threshold for regional association under a linkage peak (p < 10−5), 7 associated variants were identified in two regions under the Chr11 peak.

Conclusion

We identified a 6.5 mb area of interest on chromosome 11 associated with preserved cognitive function in Amish adults over age 75, which is near OTOG a previously reported gene associated with AD. This region merits further investigation for functional variants that might slow or prevent the development of cognitive impairment in older adults.
Diversity to discovery: Addressing health disparities in dementia research as a path to scientific breakthroughs, personalized treatment and community health
Authors: Lam Ann , Krebs Catharine , Ohayon Elan
Published: December 2020

Background

There has been growing recognition of health disparities and lack of diversity in neuroscience and the dementia field in particular. These issues manifest across multiple scales in research, clinical, and public policy domains. However, the degree to which various diversity issues and scales interconnect has been underestimated and mostly overlooked. Moreover, a focus on animal experimental systems has exasperated the problem by creating frameworks of dementia largely devoid of human diversity elements. Here we present analyses of national research resources (e.g., U.S. biobanks) and siloing of data to quantify and highlight the lack of diversity. We then forward human‐based research, clinical and public policy strategies that can help address diversity issues and help uncover foundational mechanisms across scales.

Methods

The framework includes analyses of [1] publicly available demographic data in national tissue and biospecimen banks [2] recent biological‐focused mechanistic studies that examine risk factors [3] public policy on diversity and disparities in medical and care services research.

Results

[1] Analyses of demographic data in biobanks revealed significant incongruencies in the availability of specimens for the most impacted minority groups in the United States. [2] Even in studies of genetic‐related risk factors of diverse populations, exclusion criteria made it such that mechanistic theories would be easily biased by the lack of training of researchers to the sensitivity of diversity‐related risk factors. [3] At public health and clinical trials level of investigation, researchers and Alzheimer's communities are rapidly developing more inclusive, diversity‐aware relationships and research approaches but these need to be increasingly connected to research domains to help provide biological insight into dementia pathogenesis and prevention.

Conclusions

These analyses demonstrate the need for further implementation of diversity and disparities through human‐based research programs (e.g., genetic analysis, patient‐derived cell cultures, biospecimen studies, computational modeling, etc.), as well as greater transparency in funding allocations and policies that integrate complex diversity factors into mechanistic, phenomenology and community‐level studies of dementia. Human‐based preclinical approaches can all provide greater insights and new models for personalized prevention and intervention but will need to directly include diversity‐related elements in research design in order to forward discovery.
Barriers to recruitment for research procedures in studies of Alzheimer’s disease and related disorders
Authors: Hofmann Bailey L , Serrano Kristen Jade , Shifflett Benjamin , Gigliotti Christina , Little Emily A , Salmon David P , Peavy Guerry M
Published: December 2020

Background

Females and individuals of Latinx ethnicity have increased risk of developing Alzheimer’s Disease (AD) but are underrepresented in neurodegenerative research. It is critical to understand reasons for this underrepresentation so they can be addressed to ensure that findings are generalizable to the entire population. A potential barrier to AD research is willingness to participate in relatively invasive research procedures (e.g., lumbar puncture (LP), amyloid PET imaging). This willingness may vary by demographic/ethnicity factors thereby producing disparities in research participation. The purpose of this study is to investigate whether gender, education, age, and ethnicity are associated with willingness to participate in research procedures commonly used in observational studies and clinical trials of neurodegenerative disease.

Method

A questionnaire that assessed demographics and willingness to participate (yes/no/maybe) in various research procedures [i.e., blood draw, magnetic resonance imaging (MRI), LP, amyloid PET imaging, brain autopsy, clinical trials] was administered in English or Spanish to 81 individuals (mean age=73.2+7.8; mean education=13.7+5.2) after they completed cognitive testing as part of community Memory Screening events. There were 32 Latinx and 49 non‐Latinx participants. There were 29 males and 50 females (gender unreported by two). Willingness to participate was reclassified into binary (yes/not yes) measures. Logistic regression models simultaneously controlling for age and education with gender and ethnicity as predictor variables were used.

Result

Overall, a majority of participants were amenable to blood draw (84.5%‐yes), MRI (77.8%‐yes), Amyloid PET (56.8%‐yes), brain autopsy (61.7%‐yes), and observational study (68.8%‐yes). A smaller percentage were amenable to LP (34.6%‐yes) and clinical trials (41.8%‐yes). Women were less likely than men to express willingness to agree to amyloid PET imaging (Odds Ratio: 0.18; p‐value < 0.05). Higher education level was associated with higher odds of willingness to participate in a clinical trial (Odds Ratio: 1.28; p‐value < 0.01). Ethnicity and interaction effects between gender and ethnicity had no statistically significant effects on agreement to specific procedures.

Conclusion

The findings reveal that gender and education are important in predicting attitudes toward participation in specific types of research procedures. These results could help inform recruitment strategies that maximize participation of underrepresented groups in research.
Investigating whether fractional anisotropy is associated with reduced reaction time cost on an attentional control task
Authors: McKay Nicole Sarah , Gordon Brian A. , Strain Jeremy F , Wang Qing , Morris John C. , Balota David A. , Benzinger Tammie L.S.
Published: December 2020

Background

Previous research has shown that with age and disease, the integrity of white matter (WM) structures can decline. One such measure of WM integrity is fractional anisotropy (FA), where lower values are often associated with disrupted WM. Similarly, previous work has highlighted that attentional control also declines with age and disease. It was therefore of interest to investigate whether FA was associated with cognitive ability in an aging population. To assess this, we derived a measure of attentional control performance from the Consonant‐Vowel, Odd‐Even (CVOE) task.

Method

246 participants aged 42‐87 years (M = 69, SD = 8.5), who were enrolled in studies at the Knight ADRC, were included in this analysis. Participants were classified as cognitively normal (CDR = 0, n = 185), or cognitively impaired (CDR > 0, n = 61). All participants completed an MRI, and the CVOE task. Tract‐Based Spatial Statistics (TBSS) were run on FA maps calculated for the participants. We used reaction time (RT) cost, the burden caused by the most difficult aspects of this task, as our behavioral measure of interest. This measure was calculated as the difference between RTs on congruent vs incongruently ordered trials.

Result

Using TBSS, we found that the relationships between FA and RT‐cost were significantly different for each group (Figure 1). More specifically, we found no relationship between RT‐cost and FA in our cognitively normal individuals (r = 0.14, p = 0.052; Figure 2). In contrast, we do observe a significant negative relationship between RT‐cost and FA in our cognitively impaired individuals (r = ‐0.64, p < 0.01; Figure 3).

Conclusion

Overall, we found a strong relationship between WM integrity and cognitive performance, as measured by the CVOE task. That is, as integrity becomes more compromised, participants become slower at switching between trial types within the CVOE task. Importantly, this relationship is only observed for individuals who are cognitively impaired. Taken together, our results add to a body of literature that report a relationship between WM integrity and cognitive performance, but hint that further development of more sensitive cognitive tasks may be needed to fully understand this relationship.
Sex differences of innate immune activation in amyloid positive predementia cases
Authors: Kirsebom Bjørn Eivind , Nordengen Kaja , Selnes Per , Torsetnes Silje Bøen , Sharma Kulbhushan , Gisladottir Berglind , Fladby Tormod
Published: December 2020

Background

Innate immunity is linked to Alzheimer’s disease, as shown by genome‐wide association studies and experimental data. There is, however, a sexual dimorphism in the activation of the innate immune system. Here, we investigate sex‐differences in immune activation by comparing glial activation markers in CSF from males and females with amyloid pathology as compared to healthy controls.

Method

A total of 110 CSF Aβ‐ healthy controls (n=52 males and n=58 females), and 121 CSF Aβ+ (n=70 males and n=51 females) non‐demented cases with cognitive symptoms from the Dementia Disease Initiation (DDI) cohort were included in the analyses. CSF levels of sTREM2, YKL‐40 and MCP‐1 were determined using Mesoscale Discovery. Amyloid pathology was determined using CSF Aβ1‐42 threshold of 708 pg/mL. CSF total tau was included in our models to investigate potential sex differences of active neurodegeneration. We compared CSF concentrations using three‐way ANCOVA with age as a covariate, investigating main effects, two‐way interaction effects between sex and CSF Aβ status and three‐way APOE‐ε4 interactions with sex and CSF Aβ.

Result

Significant interaction effects between sex and CSF Aβ status showed lower CSF YKL‐40 (p<.001), sTREM2 (p<.05) and MCP‐1 (p<.0001) levels in Aβ+ women as compared to males. No differences in levels were found between male and female healthy controls. Furthermore, we found that only Aβ+ males had increased YKL‐40 (p<.001), sTREM2 (p<.05) and MCP‐1 (p<.05) levels compared to healthy controls, whilst Aβ+ females showed no significant differences in levels. Men had slightly higher levels of CSF total tau as compared to women, however, this difference did not reach the threshold for statistical significance (p=.07). No main effects or interaction effects with APOE‐ε4 were found.

Conclusion

We found consistent differences in innate immune activation in Aβ+ females, but not related to APOE‐ε4 genotype. However, a slight non‐significant increase in a CSF marker of neurodegeneration in men may in part contribute to the observed differences in immune activation in our sample. The low level of innate immune activation has yet to be linked to differences in disease progression.
Relationship of hearing impairment with MRI brain volumes and cognitive decline in the Atherosclerosis Risk in Communities study
Authors: Deal Jennifer A , Power Melinda C , Betz Joshua , Reed Nicholas S , Albert Marilyn S , Gottesman Rebecca F , Resnick Susan M , Sharrett Richey , Jack Clifford R , Lin Frank R
Published: December 2020

Background

Hearing impairment is associated with cognitive decline but whether it is a cause or marker is unknown. We investigated the association of hearing impairment with brain volumes and 8‐year cognitive decline. Because the superior temporal gyrus (STG) is the location of the primary auditory cortex, we stratified results by STG volume to investigate if the association of hearing and cognition differed among participants with and without evidence of possible hearing‐related brain atrophy.

Method

We used data from 1195 community‐dwelling adults (72‐94 years, 61% female, 36% black) from the Atherosclerosis Risk in Communities Study. A composite cognitive score was created from 10 neuropsychological tests administered at 3 study visits spanning 8 years (2011‐13 to 2018‐19). Brain volumes were calculated from structural magnetic resonance imaging scans for 6 regions of interest. Pure tone air conduction hearing thresholds (frequencies 0.5‐4 kHz) were obtained in 2016‐17 and averaged, with better‐ear hearing impairment defined as an average >25 dB. Multivariable‐adjusted linear regression was used to estimate cross‐sectional differences in standardized brain volumes, adjusting for intracranial volume, demographic and clinical covariates. We estimated differences in annual rates of cognitive change by hearing impairment status adjusting for demographic and clinical covariates using linear mixed models; results were stratified by intracranial volume‐adjusted STG volume (below vs. equal to or greater than the median value).

Result

The mean STG volume difference comparing hearing impairment to normal hearing was ‐0.121 standard deviations (SD) (95% CI: ‐0.213, ‐0.028). Overall, the difference in the rate of cognitive decline associated with hearing impairment was ‐0.014 SD (‐0.023, ‐0.005). Hearing was more strongly associated with cognitive decline among participants with smaller STG volumes; rate difference, ‐0.014 SD (‐0.027, ‐0.002) compared to ‐0.008 (‐0.022, 0.006) for participants with larger STG volumes.

Conclusion

Hearing impairment was associated with smaller brain volumes in the primary auditory region, but not with other regions. Our stratified analysis suggests that hearing treatment might be an important possible strategy to delay cognitive decline, even among participants with hearing‐related brain atrophy. Furthermore, the adverse cognitive effects of hearing impairment could potentially be mitigated if early hearing treatment can prevent STG atrophy.
Cerebrospinal fluid insulin concentration increases and correlates with memory improvements after intranasal insulin administration
Authors: Kellar Derek A. , Register Thomas C. , Dahl Deborah , Craft Suzanne
Published: December 2020

Background

There are currently no effective treatments for Alzheimer’s disease (AD) which has prompted research into alternative therapeutic options; one such promising option is intranasal insulin (INI). Although INI treatment over 4 months improved memory, no study has verified whether INI administration elevates insulin in the central nervous system and whether elevations are accompanied by enhanced memory performance.

Method

This study examined the effect of acute INI administration on cerebrospinal fluid (CSF) insulin levels and memory measured by the auditory‐verbal learning task (AVLT) in mild cognitive impairment (MCI, n=11, mean age=68+‐4.8) and cognitively unimpaired adults (n=8, age=67.5+‐4.1). Participants were randomized to receive insulin (Humulin‐R 20 IU) or placebo at their first visit using an intranasal delivery device and returned two‐to‐six weeks later to repeat the visit with the other substance. Fasting participants underwent a blood draw, INI or placebo administration, AVLT, lumbar puncture (LP), blood draw, and delayed AVLT. CSF and plasma insulin measured with ultra‐sensitive ELISA and AVLT scores were compared between placebo and insulin visits. Linear modeling was performed in SAS with visit as a repeated factor and covariates BMI, cognitive status, sex, age, race, and Montreal Cognitive Assessment (MOCA) score. Non‐contributory covariates (p>0.15) were removed.

Result

CSF insulin concentration increased after INI administration (p<0.05) while peripheral insulin levels remained unchanged. INI also trended to increased AVLT immediate recall (p<0.1). CSF insulin concentration changes and AVLT changes were positively correlated (p< 0.05). Participants with higher baseline MOCA scores showed greater increases in CSF insulin after INI relative to placebo administration (p<0.05).

Conclusion

INI is effectively transported into the CNS without modulating peripheral levels. In the brain, insulin may act to increase cognition in a concentration‐dependent manner. INI may be a good therapeutic option for adults with MCI or AD for whom CSF insulin levels are enhanced through intranasal delivery.
Association between left hemisphere MK6240 uptake and language dysfunction in aging and Alzheimer’s disease
Authors: Poltronetti Nina Margherita , Rahmouni Nesrine , Lussier Firoza Z , Stevenson Jenna , Stevenson Alyssa , Benedet Andréa Lessa , Tissot Cécile , Pascoal Tharick A. , Chamoun Mira , Kang Min Su , Therriault Joseph , Savard Melissa , Mathotaarachchi Sulantha , Gauthier Serge , Rosa‐Neto Pedro
Published: December 2020

Background

Alzheimer’s disease (AD) is characterized by a progressive deterioration of multiple cognitive domains. The relative effect of amyloid plaques, neurofibrillary tangles and neurodegeneration on cognitive decline, more specifically in the language‐related areas, is still unclear. The objective of this study was to investigate the independent effects of Amyloid‐β, Tau and neurodegeneration on language using The Boston Naming Test.

Method

The present study was conducted in a population of 163 individuals (116 cognitively unimpaired, 33 mild cognitively impaired and 14 AD). Boston naming Test (BNT) was used to measure the confrontational word retrieval in individuals. Tau was assessed with [18F]MK6240. [18F]MK6240 standardized uptake value ratios (SUVRs) used the cerebellum grey matter as the reference region and were calculated between 90‐110 min post‐injection. A voxel‐based regression model evaluated the relationship between BNT and [18F]MK6240, adjusting for age, sex, years of education, diagnosis. Analyses were corrected for multiple comparisons using random field theory at p<0.001.

Result

In the present study, negative associations were observed between the levels of BNT scores and accumulation of tau indexed by [18F]MK6240‐PET. The brain regions affected were the medial frontal, parietal and temporal lobes, with a predominance in the left hemisphere.

Conclusion

These results support the claim that only tau seems to be related to language dysfunction in aging and AD. Associations were more pronounced in the left hemisphere, recapitulating known functional neuroanatomy of language production in humans. Our results support the emerging concept that tau pathology is a major driver of local neurodegeneration and domain‐specific cognitive impairment.
Changes in body mass index in young adulthood and late‐life dementia risk in a large diverse cohort
Authors: Gilsanz Paola , Mayeda Elizabeth Rose , George Kristen M. , Peterson Rachel , Eng Chloe W. , Glymour M Maria , Quesenberry Charles P , Whitmer Rachel A.
Published: December 2020

Background

Midlife obesity is associated with dementia risk, yet the relationship between body mass index (BMI) during young adulthood and dementia is unclear.

Method

We evaluated 6,947 members of an integrated healthcare delivery system who underwent clinical exams in their 20s and 30s starting in 1964‐1973 and were members as of 1/1/1996. Individuals were classified as underweight (18.5‐25.0 kg/m2), normal weight (18.5‐25.0 kg/m2), overweight (25.0‐30.0 kg/m2), or obese (30+ kg/m2) based on BMI calculated with height and weight measured during the first MHC visit from each age range. Changes in BMI were classified as: 1) consistently normal‐/over‐weight, 2) obesity onset, 3) obese to normal‐/over‐weight, and 4) consistently obese. Dementia diagnoses were abstracted from electronic medical records from 1/1/1997‐9/30/2017. Cox proportional hazard models adjusted for age (as time scale), race/ethnicity, sex, and education evaluated associations between BMI and BMI change categories with dementia risk overall and by sex.

Result

The sample was 61.7% female, 6.7% were obese in their 20s, 11.1% were obese in their 30s, and 3.5% experienced dementia during follow‐up. Individuals who were obese in their 20s were at elevated dementia risk (HR=2.14, 95% CI:1.43‐3.20) compared to normal weight counterparts; there was no difference in dementia risk among underweight individuals (HR=0.70, 95% CI:0.31‐1.59) or overweight individuals (HR=1.80, 95% CI 0.79‐1.49). Individuals who were overweight (HR=1.35, 95% CI:1.00, 1.82) and those who were obese (HR=1.76, 95% CI: 1.21‐2.57) in their 30s were at elevated dementia risk compared to normal weight counterparts; there was no association between being underweight and dementia risk (HR=0.59, 95% CI: 0.19‐1.86). Individuals who were consistently obese had more than double the risk of dementia (HR=2.42, 95% CI:1.61‐3.65) than consistently normal‐/over‐weight individuals; there was no association between obesity onset or going from obese to normal‐/over‐ weight and dementia risk. The associations between BMI in one’s 20s, BMI in one’s 30s, and BMI change with dementia risk did not significantly differ by sex.

Conclusion

Obesity during young adulthood (i.e. 20s and 30s) and being overweight during one’s 30s were associated with elevated dementia risk. Consistent obesity during young adulthood more than doubled an individual’s risk of dementia.
TNF‐β inhibitors in preventing mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD): An updated retrospective review using both EMR and claims data
Authors: Stacey Jennifer L.
Published: December 2020

Background

It is widely believed that inflammation contributes to the pathogenesis of AD. TNF‐α has been implicated in both AD and neurological inflammation. Previous research found anti‐TNF‐α therapies to be of potential benefit for preventing AD, and here updated analyses further contribute to this research while incorporating preceding diagnoses as potential outcomes.

Method

Patients were identified as either receiving an anti‐TNF‐α drug (etanercept, adalimumab, certolizumab, infliximab, or golimumab) or patients who were anti‐TNF‐α naïve receiving methotrexate (MTX). Patient cohorts were generated in both an electronic medical records (EMR) research network of 59M patient lives and a 201M patient network of linked primary care data with medical and pharmacy claims. Neither cohort had MCI (ICD‐9 331.83 or ICD‐10 G31.84), dementia (ICD‐9 290 or 294.1 or 294.2 or ICD‐10 F02 or F03), or AD (ICD‐9 331.0 or ICD‐10 G30) prior to the outcome window. The risk of MCI, dementia, and AD from 1 year after first exposure to either anti‐TNF‐α or MTX were analyzed using measures of association and survival analysis conducted via Kaplan‐Meier estimator. Cohort comparisons were run with propensity score matching (PSM) to control for demographic, comorbidity, medication, and diagnostic procedure confounders.

Result

There was significant MCI, dementia, and AD prevention with anti‐TNF‐α treatment compared to MTX found in both EMR and claims data networks without and with PSM. Only exception was EMR outcomes of AD with PSM (Risk Difference 0.04%; 95% CI (‐0.003%,0.079%); p=0.0679). [See Table 1]. Time to outcomes were measured up to 7,000 days in the EMR cohort up to 6,000 days post index in the claims cohorts.

Conclusion

This study provides further RWD based evidence that points to anti‐TNF‐α therapies as a beneficial therapy in the prevention of MCI, dementia, and AD. Further research is warranted to investigate these findings in larger cohorts and for outcomes to be monitored in a longer observation window.
Accuracy of test battery harmonization: Simulation results using the HRS and MHAS studies
Authors: Koscik Rebecca L , Gavett Brandon E , Ma Yue , Ilango Sindana , Eng Chloe W , Helfand Benjamin KI , Trittschuh Emily H , Mungas Dan M
Published: December 2020

Background

Standardized measures of cognitive function are often used in research to understand predictors of heterogeneity in cognitive aging. Increasingly, researchers seek to pool data across studies. When assessment protocols contain overlapping items, item response theory and associated analytical techniques can be used to combine test items across studies into harmonized cognitive outcome(s). To better understand how characteristics of test item overlap impact a harmonized outcome, this study uses psychometric data from two cognitive aging studies to simulate and compare the accuracy of harmonization across six total items/overlapping items scenarios.

Method

Item‐level cognitive data from 19 unique items across the Health and Retirement Study (HRS; 12 items) and the Mexican Health and Aging Study (MHAS; 10 items) were used (Table 1). Item response theory (IRT) calibration of a unidimensional model using data from the combined sample yielded item parameter and ability (theta) estimates that were then used to simulate six scenarios exploring item count and overlap combinations (19/19, 12/12, 10/10, 19/4, 19/3, and 19/1 for total/overlapping (akak “linking”) items, respectively). Briefly, simulation methods were: generate 500 simulated item‐level data sets with two groups (n = 500/group), each group having mean(sd) true ability set equal to HRS and MHAS estimates, respectively; apply IRT calibration to each simulated dataset, generating factor scores (using expected a posteriori (EAP) method); accuracy of harmonization was quantified by the difference between the IRT‐estimated factor scores and thetas for each simulated dataset using root mean square error (RMSE).

Result

RMSE generally improved (decreased error) with increasing numbers of overlapping tests and linking items (Fig1). Differences between group means were poorly reproduced with <4 linking items (Fig2). The scenario representing the true overlap of three items between MHAS and HRS items (19/3) did not reproduce means(sd) well (suggesting that, without at least one additional linking item with desirable measurement properties (scenario 5), these tests may not be harmonized accurately.

Conclusion

Future simulations should attempt to disentangle the effects of linking item quantity and characteristics (e.g. range of difficulty) from the effects of differences in group means and standard deviations on RMSE.
Genome wide association study of chronic traumatic encephalopathy
Authors: Atherton Kathryn , Khan Mohammed Muzamil , Shea Conor , Chung Jaeyoon , Nair Evan , Baucom Zachary H. , Abdolmohammadi Bobak , Uretsky Madeline , Martin Brett M. , Palmisano Joseph , Farrell Kurt W. , Cherry Jonathan D. , Alvarez Victor E. , Huber Bertrand R. , Alosco Michael L. , Lunetta Kathryn L. , Tripodis Yorghos , Stein Thor D. , Farrer Lindsay A. , Crary John F. , McKee Ann C. , Mez Jesse
Published: December 2020

Background

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI). CTE has distinct neuropathology defined by perivascular hyperphosphorylated tau (ptau) deposition. The presence and severity of CTE pathology varies among those with similar RHI exposure, suggesting a role for non‐RHI risk factors, including genetics. Here we conducted the first genome‐wide association study (GWAS) of neuropathologically‐confirmed CTE.

Method

175 brain donors from the Veterans Affairs‐Boston University‐Concussion Legacy Foundation Brain Bank with known exposure to RHI in the form of contact sports and/or military service were assessed for CTE pathology. CTE pathology was staged on a semiquantitative scale from 0 to 4 (0 = absent; 4 = most severe). Ptau burden was also assessed across 11 brain regions commonly affected in CTE on a semiquantitative scale from 0 to 3 (0 = absent; 3 = most severe). We tested the association of genome‐wide genotyped and imputed single nucleotide polymorphisms (SNPs) with CTE stage in a linear regression model adjusted for 10 principal components of population substructure. We tested the association of top hits with ptau burden in each of the 11 brain regions.

Result

Two loci achieved genome‐wide significance: top SNP rs63565460 [minor allele frequency (MAF) = 0.08; beta = ‐1.64; p = 2.4 × 10−8] is an intronic SNP in PIP5K1B on chromosome 9; and top SNP rs12447028 (MAF = 0.07; beta = ‐1.84, p = 2.6 × 10−8) is an intronic SNP in ABAT on chromosome 16. The PIP5K1B locus had the largest effects in cortical regions. PIP5K1B is expressed in brain and has been associated with intelligence in GWAS. The ABAT locus had the largest effects in the inferior orbital gyrus and the locus coeruleus. ABAT is expressed in brain and has been associated in GWAS with anger proclivity, a symptom of CTE. The ABAT protein functions in GABA catabolism.

Conclusion

In the first GWAS of CTE, two promising loci in PIP5K1B and ABAT achieved genome‐wide significance. Both loci had the largest effects in brain regions affected early in CTE. Efforts to enlarge the sample size, incorporate measures of RHI exposure and test additional endophenotypes are underway. Identified loci may implicate disease mechanisms, provide targets for therapies, and guide counseling of athletes regarding risk of play.
Association between depressive symptoms and cognitive function in older adults with type 1 and type 2 diabetes compared to those without diabetes
Authors: Lacy Mary E. , Gilsanz Paola , Eng Chloe W. , Beeri Michal Schnaider , Karter Andrew , Whitmer Rachel A.
Published: December 2020

Background

Depression is a major risk factor for cognitive impairment among people with type 2 diabetes (T2D) and the general population. Depression is 3 times more prevalent among people with type 1 diabetes (T1D) than in the general population and interferes with self‐management. Understanding the association between depression and cognitive function in older adults with T1D is crucial.

Method

Using baseline data from the Study of Longevity in Diabetes (SOLID), we examined the association between depressive symptoms and cognition in older adults with T1D (n=799), T2D (n=240), and without diabetes (n=256 matched on age, sex, race/ethnicity, and education). Based on recommended guidelines, a score of >5 on the 15‐item Geriatric Depression Scale indicated presence of depressive symptoms. Cognitive function was evaluated at baseline. Factor analyses identified the following cognitive domains: executive function (Trail Making A and B, Digit Symbol Substitution, and Stroop Interference Test), language (List sorting, MINT, Phonemic and Category fluency), simple attention (Diamond and TMX cancellation), verbal episodic memory (Word List Learning), and visual episodic memory (Benson). All cognitive scores were standardized (mean=0; SD=1). Linear regression models evaluated the association between depressive symptomatology and cognitive function adjusting for age at interview, sex, race/ethnicity, and education.

Result

Subjects (mean age of 67.9 years and 50.9% were female) with diabetes had a greater prevalence of depressive symptoms than those without diabetes (T1D: 9.8%; T2D: 9.2%; no diabetes: 2.7%; chi‐square p‐value=0.002). In T1D, depression was associated with poorer performance on the language, executive function, and verbal episodic memory domains (Table 1). In T2D, depression was associated with poorer performance on the executive function domain. There was no observed association between depression and cognitive function among those without diabetes.

Conclusion

Among older individuals with T1D, depressive symptoms were associated with lower scores on a range of cognitive domains. By contrast, depressive symptoms were only associated with executive function in T2D and were not associated with any cognitive domains in those without diabetes. Our findings underscore the importance of mental health as a key component of healthy aging in older adults with T1D and T2D.
Is statin related to conversion of mild cognitive impairment to dementia?
Authors: Cintra Marco Túlio , Ávila Rafaela , Lage Ariane Flávia , de Oliveira Hansen Erika , Costa Mônica Vieira , Rocha Divino Pedro Alves , Bicalho Maria Aparecida
Published: December 2020

Background

Although randomized controlled trials have not confirmed cognitive impairing effects of statins, continuing evidence suggests statins have the ability to cause reversible cognitive impairment in some patients. Paradoxically, statins have also been shown to decrease risk of dementia, Alzheimer’s disease, and to improve cognitive impairment in some cases. However, randomized controlled trials have similarly failed to find the beneficial effect. We conducted evaluate the effect of statin on the conversion of mild cognitive impairment (MCI) to dementia in a Cohort of elderly individuals without functional and cognitive impaiment (NC) and with MCI patients.

Method

Cohort was reassessed annually by geriatricians and neuropsychologists for an average period of 3.01 ± 1.43 years. The effect of statin on cognition was evaluated when it was in use throughout the follow‐up period and, it was in use at any time during the follow‐up. Chi‐square and Fisher tests (categorical variables) and student t tests, ANOVA, Mann Whiney (continuous variables) were used.

Results

176 individuals were selected (53 CG, 111 with amnestic MCI ‐ aMCI‐ and 12 with non‐amnestic MCI ‐naMCI), aged 76.52 ± 7.27 years, 69% female and 3.61 ± 3.23 years of schooling. We observed conversion of aMCI to dementia in 27 participants (92.6% Alzheimer dementia), corresponding to a conversion rate of 24.3%. In the aMCI group, the remission rate was 13.5%. 51.1% of the sample received statin at some point during the follow‐up and 30.7% used it throughout the study. 98.8% of prescribed statins had moderate potency. Comparing stable MCI group throughout the study with the group which progressed to dementia, the group that used it any time during the follow‐up analysis showed a p‐value of 0.104, whereas the group that used it during the entire follow‐up showed a p‐value of 0.166. Comparing remission and conversion groups, the one that used statin any time during the follow‐up showed a p‐value of 0.542, patients who received statin during the entire follow‐up had a p‐value of 0.746.

Conclusion

Statins were not associated with conversion from aMCI to dementia, even when used throughout the entire follow‐up.
Association of cerebral white matter disease with cardiovascular risk factors, amyloid accumulation, and cognition
Authors: Cody Karly Alex , Berman Sara E , Koscik Rebecca L. , Rivera‐Rivera Leonardo A , Hoffman Carson A , Erickson Claire M , Mueller Kimberly D , Clark Lindsay R , Chin Nathaniel A. , Christian Bradley T , Rowley Howard A. , Wieben Oliver , Johnson Kevin M , Betthauser Tobey J , Johnson Sterling C. , Eisenmenger Laura
Published: December 2020

Background

Understanding cerebrovascular health in Alzheimer’s disease (AD) is vital, as the majority of individuals with dementia due to AD are also found to have vascular disease at autopsy. We examined the relationships between centrally and peripherally measured vascular health markers and amyloid accumulation across the AD clinical spectrum.

Method

Cerebral white matter (WM) disease was determined by a neuroradiologist using the Cardiovascular Health Study (CHS) score in 236 individuals (75% cognitively healthy, 25% cognitively impaired; Table 1) from the Wisconsin ADRC and WRAP cohorts. A subset (n = 73) of individuals completed [C‐11]PiB PET imaging. Metrics of internal carotid arterial (ICA) health assessed by 4D‐flow MRI as well as WM hyperintensity lesion volume (WMH‐LV), amyloid accumulation, vascular risk factors, and cognitive status were examined across individuals with high (≥3) and low (<3) CHS scores (Table 2, Figures 1 & 2). A threshold for vascular positivity (V+/‐) was identified as 1.5SD>the mean %WMH‐LV of total intracranial volume in individuals with CHS<3. Participants were classified according to their amyloid and vascular positivity status.

Result

In the larger dataset (n = 236), individuals with CHS≥3 were significantly older, more likely to be cognitively impaired, and demonstrated higher pulse pressure, lower cholesterol, and greater %WMH‐LV (Table 1, Figure 1). There was no difference between CHS groups in average ICA blood flow, ICA pulse wave velocity, or global PiB accumulation (Table 2). Neither CHS rating nor %WMH‐LV were associated with amyloid (Spearman’s rho = ‐.128, p = .280; Spearman’s rho = .078, p = .511, respectively). When using %WMH‐LV as a biomarker for cerebrovascular health, the vascular positivity threshold was 0.409%. In individuals with amyloid imaging, 54.8%(38/73) were V‐/A‐, 8.2%(8/73) were V+/A‐, 34.2%(24/73) were V‐/A+, and (2/73)0.8% were V+/A+. CHS rating and vascular positivity were not related to cognitive diagnosis in the amyloid imaging subset (Figure 2).

Conclusion

Elevated cerebral WM disease (CHS≥3) was related to greater WMH lesion burden, but not blood flow or pulse wave velocity of the ICAs. Thus far, in this sample spanning the continuum of AD, neuroimaging measures of vascular health were not related to amyloid, suggesting independence of these pathologies. Investigations into the associations between amyloid, cerebrovascular health, and cognition are ongoing as more data become available.