bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive outcome measures used for assessing urban and rural disparities in dementia and cognition: A scoping review
Authors: Valdivieso‐Mora Esmeralda 
Published: December 2022

AbstractBackgroundEvidence of disparities in dementia and cognition by gender, race/ethnicity, and income‐level of countries has long been available. A growing body of literature examining urban/rural disparities has been recently accumulating. Most of the studies comparing within‐country regions indicate that rural older adults have a greater cognitive disadvantage and higher risk for dementia than their urban counterparts. These findings are not consistent across all studies. The purpose of this study was to examine the literature on rural/urban disparities in dementia and cognitive aging.MethodA scoping review of 16 studies examining differences in dementia and cognitive functioning of urban and rural older adults was conducted. Studies were categorized by country. Relevant information from their methods was systematized, based on their populations/samples, outcome measures and main finding of cognitive advantage (rural<urban, urban>rural, rural = urban).ResultMost of the studies addressing rural and urban disparities have been conducted in large, industrialized countries. The main focus of the studies reviewed has been on comparing dementia rates, not healthy aging. Most studies have administered cognitive screening questionnaires to identify dementia cases (MMSE, Modified MMSE, Telephone Interview for Cognitive Status, CSI‐D, etc.). The criteria used to define rurality and urbanity varied from study to study.ConclusionRegions of the world with larger rural areas are underrepresented in the study of rural and urban disparities of dementia and cognitive aging. From the group of studies reviewed, important conceptual and methodological lessons were identified. The variability in the operational definition of rurality between studies is a major challenge for consolidating the literature on urban and rural disparities in dementia and cognitive aging. A culturally appropriate neuropsychological battery could be used to identify true urban and rural disparities in cognitive functioning. None of the studies examined whether the assessment tools and cognitive factors were comparable for both rural and urban older adults, assuming the tests are equivalent across regions. Research focusing on the measurement equivalence of neuropsychological batteries between rural and urban regions are warranted.
Effect of increasing participation in habitual intellectual activities on cognitive function in older adults without clinical dementia ‐ preliminary findings from a randomized controlled trial
Authors: Lee Allen TC 
Published: December 2022

AbstractBackgroundBased on our longitudinal observational study of >15,000 community‐living older adults, we previously reported that those with regular participation in intellectual activities in late life are at a lower risk of developing clinical symptoms of dementia in six years. Nevertheless, the dose‐response relationship between intellectual activities and cognitive benefits remains unclear. To address this knowledge gap, we have designed a two‐arm, parallel‐design, single‐blind randomized controlled trial, with the aim to test whether doubling calligraphy practice results in more cognitive benefits in older adults without clinical dementia.MethodCommunity‐living older adults without clinical dementia and with prior practice of calligraphy as defined by one hour of calligraphy per week were randomly allocated into either the control group where they continued their usual practice of calligraphy or the intervention group where they doubled their practice. Cognitive outcomes were assessed before and after the six‐month intervention.ResultThe preliminary data of the fourteen subjects who completed our study showed that a decreasing trend in the ADAS‐Cog score (pre = 7.1±3.2, post = 5.3±4.8, p = 0.23), an increasing trend in the delayed recall test score (pre = 8.8±0.5, post = 9.3±1.0, p = 0.48), less errors in word recognition (pre = 3.1±0.8, post = 1.7±1.2, p = 0.005), and an increasing trend in the category fluency test score (pre = 17.1±4.7, post = 18.3±2.9, p = 0.52) were found in the intervention group. Repeated measures analysis of variance showed that the improvement in word recognition was greater in the intervention group than in the control group (p = 0.01).ConclusionOur study, which is currently still ongoing, will shed light on whether increasing the “dosage” of intellectual activities could provide additional cognitive benefits to older adults and help them achieve cognitive maintenance.
Validation of a modified MOCA translation for use among Arabic‐speaking immigrants in the U.S.
Authors: Ajrouch Kristine J , Tarraf Wassim , Brauer Simon , Zahodne Laura B. , Antonucci Toni C 
Published: December 2022

AbstractBackgroundThe only validated, widely‐used dementia screen that has Arabic language norms/cutoffs is the Montreal Cognitive Assessment (MoCA). Yet, Arabic translations of the MoCA vary across countries. This study considers various Arabic translations of the MoCA, and presents a modified translation for use among Arabic‐speaking immigrants in the U.S.MethodThe modified translated version of the MoCA was administered to 32 Arabic‐speaking adults age 65+ living in metro‐Detroit. Eight (25%) had an ADRD diagnosis. To assess the reliability of the MoCA, each item was standardized and Cronbach’s alpha was calculated. To assess the similarity of ADRD and non‐ADRD respondents with regards to each MoCA item as well as with regards to demographics we used Fisher’s exact test for binary variables and t‐test for continuous variables. Ordinary least squares models were used to examine how an ADRD diagnosis predicts the MoCA score, adjusting for demographics.ResultThe mean age of the sample is 73 years old. Sixty‐two percent (62%) are female and 28% have a high school education or more. The alpha was acceptably high at .87. The MoCA item‐level scores for respondents with and without ADRD diagnoses showed that all respondents correctly identified the picture of a camel. There are also five items for which none of the ADRD respondents gave correct responses: trail‐making, verbal fluency F, both abstraction questions, and the cube‐copy test. Bivariate analyses further indicate that ADRD respondents are older than non‐ADRD respondents (p<.001). There is no significant difference in gender or education level. Those with ADRD diagnosis scored lower overall on the MoCA ( = ‐.35; se = .37), with 58% of the variation explained by the diagnosis and demographics. We interpret the result as a small effect size as indicated by the Cohen’s heuristic for the difference between means (0.2‐0.49).ConclusionThe Arabic language MoCA is able to distinguish respondents with an ADRD diagnosis. Decision points about translations should consider national contexts to maximize equivalencies across samples.
Assessing Cognitive Impairment in People with Dementia Associated Disorders: Self‐Reported Recognitive Impairment Contrasted with Computerized Multi‐Domain Cognitive Testing – Truth be Told
Authors: Kaczmarek Olivia , Baek Steven , Peraza‐Bonilla Sophia , Sethi Avtej , Bumstead Barbara , Zarif Myassar , Gudesblatt Mark 
Published: December 2022

AbstractBackgroundDementia associated diseases (DAD) are characterized by progressive impairment of cognition that interferes with an individual’s ability to function independently. Clinically, cognitive impairment (CI) can vary in degree and combination across multiple cognitive domains (CD). Clinician and patient with DAD (PwDAD) recognition of such varied types/degrees of CI might not only be sub‐optimal, but also unable to recognize subtle change and progression. Patient self‐reported outcome measures (PRO) are used to gauge CI or disability progression. Traditional measures (MOCA, MMSE) include a dichotomous outcome measure and routine neuropsychological screening might not be practical. Quantitative and objective screening across multiple CD can be accomplished in routine care with validated, examiner independent, computerized multi‐domain cognitive assessment battery (CAB‐NT, NeuroTrax). NeuroQOL Cognitive Function Short‐Form (CF‐SF) is one validated disease agnostic PRO that can be incorporated to evaluate patient perception of disease impact and change on CI. The relationship of CF‐SF to multi‐domain quantitative CAB has not been explored in PwDAD.MethodRetrospective review of consecutive PwDaD who completed both CF‐SF and CAB‐NT on the same day in the course of routine care. CAB‐NT included 7 cognitive domains: memory (Mem), executive function (Exe), attention (Att), information processing speed (Inf), visual spatial (Vis), verbal function (Ver), motor skills (Mot) as well as a global cognitive summary score (GCS).ResultsLinear regression analysis of relationship was explored with significance (p<0.05). 196 PwDAD, (65% female, average age 73+/‐ 9 years). “Significant” relationships (p<0.05) were identified through regression analysis for the following CD scores: GCS (r2 = 0.03), Exe (r2 = 0.04), Att (r2 = 0.06), and Mot (r2 = 0.04).ConclusionPwDAD self‐perception of their cognitive abilities do not accurately reflect objective CAB performance measures of cognitive function. CF‐SF PRO scores do not reflect cognitive performance across multiple cognitive domains and should not be considered appropriate screening tools to incorporate into routine care to determine when to consider the need for examiner independent measures to accurately monitor disease impact or change. Objective computerized testing measures across multiple cognitive domains provides useful insight and value based information for clinicians to gauge the presence of or change in cognitive impairment.
The Relationship of Self‐Reported Depression and Self‐Perceived Cognitive Function in People with Dementia Associated Disorders: A Complex Relationship That Requires More Than Perception and Self‐Report
Authors: Kaczmarek Olivia , Baek Steven , Peraza‐Bonilla Sophia , Sethi Avtej , Bumstead Barbara , Zarif Myassar , Gudesblatt Mark 
Published: December 2022

AbstractBackgroundDementia associated diseases (DAD) refers to multiple clinical conditions all characterized by progressive impairment of cognition that interferes with an individual’s ability to function independently due to such cognitive impairment (CI). Clinically, CI can vary in degree and combination across multiple important individual cognitive domains (CD). Depression is also reported to be an early sign of or as a potential risk factor of Alzheimer’s or another DAD. Enhanced awareness of the presence of depression in people with DAD (PwDAD) and the relationship of self‐reported depression to self‐perception of cognitive function may provide insight into current screening methods incorporated in routine care and treatment options prescribed as well as the need to include further information as treatment options become more complex and time available to holistically evaluate patient needs evolves.MethodRetrospective cross‐sectional analysis of PwDAD who completed both the patient reported outcomes (PRO) Neuro QOL Cognition Function‐ Short Form (CF‐SF) and Neuro QOL Depression‐Short Form (SFD‐SF) in routine care. Linear regression analysis of relationship was explored with significance (p<0.05).Results213 PwDAD, 65% female, average age 70 +/‐ 15 years. A statistically significant negative relationship was identified between self‐reported depression identified by Neuro‐QOL PRO SFD‐SF and self‐perceived cognition abilities (CF‐SF) (r2 = 0.25).ConclusionThere is an inverse relationship between PRO self‐reported depression and self‐reported/self‐perceived cognitive ability in PwDAD. Incorporating PRO Cognitive Function‐Short Form as the sole measure of cognitive function or simply as a screening tool to determine when to objectively measure cognitive function in PwDAD without simultaneously screening for depression and not incorporating other objective value‐added cognitive measurement tools should not be recommended.
Proteomic profiling of cognitive function in middle‐aged and elderly adults
Authors: Tin Adrienne , Fohner Alison E , Yang Qiong , Seshadri Sudha , Brody Jennifer A. , Fornage Myriam , Group The NeuroCHARGE Working 
Published: December 2022

AbstractBackgroundDementia is a pressing public health issue that affects 55 million adults worldwide. Some risk factors for cognitive decline and poor brain health appear to affect the blood brain barrier or cerebrovasculature. Therefore, it is plausible that circulating proteins may reflect causes and consequences of poor brain health. Identifying associated circulating proteins could help uncover important biological pathways in cognitive decline and dementia.MethodsWe conducted a cross‐sectional study of circulating proteins and cognitive function among participants without prevalent dementia or stroke in three cohorts: Atherosclerosis Risk in Communities (ARIC) study (n = 4,286), Cardiovascular Health Study (CHS, n = 2,297), and Framingham Heart Study (FHS, n = 706). Circulating proteins were quantified using a modified aptamer technology (SomaScan). Cognitive function was assessed by the first principal component (PC1) of measured cognitive scores from three different domains. We used linear regression to evaluate the association between each protein and PC1 controlling for age, sex, race, education level, and APOE Ɛ4 carrier status. We used fixed effect meta‐analysis to combine the cohort results from all age groups and two cohorts aged≥ 65. Statistical significance levels were Bonferroni corrected.ResultsThe mean (SD) age in years was 74 (5) in ARIC, 75 (5) in CHS, and 46 (8) in FHS. Females comprised 58% of ARIC, 62% of CHS, and 55% of FHS. The number of proteins in common was 1,019 for all three cohorts and 4,672 for ≥65 years only. Meta‐analysis identified 76 significant proteins overall (p<4.9E‐5 = 0.05/1,019) and 211 significant proteins among age ≥65 (p<1.1E‐5 = 0.05/4,672). Among the significant associations, heterogeneity was moderate (median I2 of 78% in the overall meta‐analysis and 66% in the older age group). Some significant proteins are known biomarkers of dementia, such as GDF15 and SVEP1.ConclusionsLarge‐scale proteomic profiling identified plasma proteins significantly associated with cognitive function across 3 cohorts. Further replication and characterization, such as enrichment analysis, are underway to further elucidate the relationship between these associated circulating proteins and brain health.
Detection of Amyloid status in patients with uncertain diagnosis and associations with remotely‐collected cognitive composites
Authors: Knight Krissy N , Iaccarino Leonardo , Tosun Duygu , Rabinovici Gil D. , Weiner Michael W. 
Published: December 2022

AbstractBackgroundIn an effort to build efficient and scalable screening tools for early detection of cognitive impairment, the Brain Health Registry (BHR) was created to collect demographic and cognitive information in a remote setting. A select cohort of participants enrolled in the BHR also underwent amyloid PET scans, allowing the utilization of remotely collected cognitive data for amyloid enrichment.MethodSelf‐reported measures were collected through the BHR from 656 older adults co‐enrolled in the Imaging Dementia ‐ Evidence For Amyloid Scanning (IDEAS) study with an in‐clinic diagnosis of unexplained mild cognitive impairment (MCI; n = 522) or dementia of uncertain cause (n = 134) (Table 1). Global Amyloid‐PET centiloid values were obtained via a published PET‐Only processing method. An independent pathology‐based cut‐off of 24.4 was applied to define amyloid status. A comprehensive set of BHR variables were regressed on the continuous centiloid values to quantify the association between online measures with global amyloid burden. Then, logistic regression was employed to determine the ability of BHR variables to detect amyloid positivity. Results from both regression models are provided in Table 2. Accuracy measures are reported in Table 3.ResultThe overall model fit of the BHR data with centiloid values was statistically significant (F = 4.69; p‐val<0.001), while R^2 = 0.09, highlighting the strong association with global amyloid burden and the high variability for this cohort. For both dichotomous and continuous models, family history of AD and subjective memory concern are associated with higher amyloid accumulation; higher Geriatric Depression Scale scores are associated with lower amyloid, while low scores of Memtrax N‐back test are related to higher amounts of amyloid. When applying 5‐fold cross‐validation to the logistic model, the classification accuracy of the BHR variables is 64% (cvAUC = 64%; spec = 67%; sens = 60%).ConclusionDespite high variability in BHR data, remotely collected subjective and cognitive information are associated with amyloid in older adults with unexplained MCI or dementia of an uncertain cause. The ability to detect amyloid status with online data points to the large potential for building an online screener and motivates further online data collection.
Effects of Androgen Deprivation Therapy on Alzheimer's disease and Related Dementia Risk in the Million Veteran Program
Authors: Panizzon Matthew S. , Deka Rishi , Anglin Tori , Logue Mark W. , Merritt Victoria , Chang Nai‐Chung N , Carter Hannah K , Jasuja Guneet , Lee Kyung‐Min , Lynch Julie , Pagadala Meghana , Rose Brenton , Seibert Tyler , Teerlink Craig , Tu Xin M , Hauger Richard L. 
Published: December 2022

AbstractBackgroundAndrogen deprivation therapy (ADT) for prostate cancer depletes circulating testosterone levels and has been shown to increase risk for Alzheimer’s disease (AD) and related dementias (ADRD). It is unclear whether ADT acts independently to increase ADRD risk, or whether effects of this treatment are exacerbated by the genetic risk for AD. We hypothesized that the effect of ADT on ADRD risk will be moderated by AD polygenic risk.MethodClinical and genetic data were analyzed from 87,060 United States Veterans, who had a diagnosis of prostate cancer and were participants in the Million Veterans Program (MVP) biorepository study. Clinical conditions, including diagnosis codes for ADRD, cancer, Charlson Comorbidity Index conditions, laboratory values (Gleason score, Prostate Specific Antigen levels), cancer treatments, and vital status were obtained from the Veterans Affairs (VA) longitudinal electronic health record data. A polygenic risk score (PRS) for AD was derived based on summary statistics from the Kunkle et al (2019) GWAS of Alzheimer’s disease. The impact of ADT on ADRD was assessed using a time‐varying Fine‐Gray competing risks regression. Death from any cause was considered as a competing event to the development of ADRD.ResultThere were 17,092 (19.6%) patients who received ADT. 72% of the cohort was of white/European ancestry. The average age at prostate cancer diagnosis was 66 years. The median duration of ADT was 360 days. ADT users were more likely to be African American, and had higher PSA levels and Gleason Scores. ADT exposure and the AD PRS each showed significant main effects on ADRD risk, HRs = 1.16 (95% CI: 1.04 ; 1.29) and 1.10 (95% CI: 1.06 ; 1.15) respectively; however, we did not observe a significant interaction effect. Sensitivity analyses indicate that the association was not confounded by including Gleason score, PSA level, income, or education, and results were not altered significantly by excluding or focusing on the effect of the APOE:E4 locus.ConclusionADT significantly increases risk of ADRD, independent of underlying AD genetic risk factors. Further research is necessary in order to determine the mechanism by which androgen depletion contributes to the pathophysiology of ADRD.
TMEM176B regulates phagosome maturation of glial cells and its increased activity contributes to the therapy of Alzheimer’s disease
Authors: Park Seongjeong , Lee Juho , Yoo Miran , Seo Jinsoo , Chung Won‐Suk , Kim Hye‐Ju 
Published: December 2022

AbstractBackgroundGiven recent interest in using amyloid b (Aβ)‐targeted antibodies as a therapy for patients with Alzheimer’s disease (AD), removal of Aβ by phagocytosis likely protective early in AD. Impaired phagocytic function of glial cells surrounding Aβ plaques during later stages in AD likely contributes to worsened disease outcomes, therefore enhancing phagocytic activity of glial cells could be a potent strategy for AD therapy.MethodChanges in TMEM176B expression according to the progression of AD pathology was assessed by measuring TMEM176B protein in human AD brain lysates and TMEM176B transcripts in Ab‐treated primary rat astrocytes. The roles of TMEM176B in phagosome maturation of glial cells was investigated by measuring Rab5, Rab7, LAMP1, LAMP2, cathepsin D, and LC3B in presence of Aβ. Intracellular pH of glial cells was detected using fluorescent dye‐based pHrodo Red AM intracellular pH indicator (Invitrogen, Carlsbad, CA). In 5xFAD and 3xTg AD mice model, therapeutic effects of AAV‐TMEM176B was examined. AAV (adenovirus‐associated virus)‐TMEM176B (1 – 2×1010 GC) was intracerebroventricularly injected, and Aβ plaque and p‐tau in brains were assessed 3 months later. Behavioral studies such as Y‐maze, Morris water maze, and novel‐object‐recognition were conducted to exam the effect of TMEM176B overexpression in alleviation of cognition decline.ResultIn human AD brains, Tmem176B expression was increased in moderate AD (Braak III‐IV) was decreased in severe AD (Braak V‐VI). TMEM176B was upregulated by acute Aβ treatment in primary rat astrocytes, and was gradually downregulated concomitantly with impairment of Aβ phagocytosis activity by chronic exposure to Aβ. The TMEM176B agonistic compound augmented phagosome maturation and phagosomal acidification, which led to increased Aβ phagocytosis and lysosomal degradation. Studies confirmed that intracerebroventrical administration of AAV carrying TMEM176B in AD mice results in enhanced glial phagocytosis followed by lowered Aβ burden in brain. Moreover, overexpression of TMEM176B by AAV injection significantly improved cognition impairment of AD mice.ConclusionData from these studies suggest that TMEM176B plays a direct and critical role in phagolysosmal function of glial cells and AD pathogenesis and highlight this ion channel as a potential therapeutic target for treating AD.