bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with levels of plasma markers of amyloid pathology and neurodegeneration in a population‐based sample
Authors: Syrjanen Jeremy A. , Campbell Michelle R. , Algeciras‐Schimnich Alicia , Vemuri Prashanthi , Graff‐Radford Jonathan , Machulda Mary M. , Knopman David S. , Jack Clifford R. , Petersen Ronald C. , Mielke Michelle M. 
Published: December 2021

AbstractBackgroundBlood‐based biomarkers of amyloid pathology and neurodegeneration are entering clinical use. It is critical to understand what factors affect these plasma marker levels for accurate clinical interpretation. Herein we examined factors associated with plasma Ab42, Ab40, neurofilament light (NfL), total tau (T‐tau), and the ratio of Ab42 to Ab40 (Ab42/40).MethodThe plasma markers were measured for 996 participants (859 cognitively unimpaired [CU], 133 mild cognitive impairment [MCI], 4 dementia) from the Mayo Clinic Study of Aging (MCSA), aged 51 to 95 years. The Quanterix Simoa® HD‐1 analyzer was employed to measure the plasma markers using the Simoa® Neurology 3‐Plex A (N3PA) (T‐tau, Ab42, Ab40) (catalog #101995) and the Simoa® NF‐light (catalog #103180). All other data was collected during in‐person MCSA visits or abstracted from the medical record. Statistical significance was determined using an alpha level of 0.05.ResultAmong CU, all of the plasma markers showed correlation with age. T‐tau (Spearman’s rho = 0.113, p<0.001) showed the weakest correlation and NfL (rho = 0.695, p<0.001) had the strongest. Women had higher levels of T‐tau (Median women: 2.782 vs. 2.390, p<0.001) and lower Ab42/40 (0.033 vs. 0.035, p=0.024) compared to men. In linear regression models predicting z‐scored plasma markers and adjusted for age and sex, several statistically significant predictors were found. For example, higher Charlson comorbidity index and chronic kidney disease were associated with higher levels of all markers; slower gait speed was associated with higher levels for all but Ab42/40 where no relationship was seen. A higher BMI was associated with higher levels of Ab42, Ab40, and T‐tau whereas NfL tended to be lower with increased BMI. Among participants with MCI or dementia, the relationship between gait speed or chronic kidney disease with NfL and T‐tau strengthened considerably.ConclusionMultiple variables affect plasma markers of amyloid pathology and neurodegeneration among CU in the general population. Some relationships differed among MCI and dementia participants. Incorporating this information is critical for accurate interpretation of the marker levels and for the development of reference ranges.
Precognize pilot study: A visuomotor ability‐based novel screening method for Alzheimer’s disease?
Authors: Berente Dalida Borbala , Kamondi Anita , Horvath Andras Attila 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is the leading cause of dementia in the elderly. In the early stages, cognitive decline starts with the involvement of episodic memory. Latest results suggest that impairment in visuomotor function also appears in the initial stages of the disease which may have diagnostic potential.Method52 AD patients underwent neuropsychological evaluation including Addenbrooke Cognitive Examination (ACE). The patients were then divided into three groups based on disease duration in years (y) (1:≤2y N=15; 2: 2‐4y N=26, 3:≥4y N=11). Cognitive subscores were analyzed with group comparisons and Spearman analysis was applied on ACE subscores and disease duration. Based on these results, our group developed an electronic test battery (Precognize). It is based on the trail‐making test and used for detecting and analyzing mouse movements. To test the accuracy of our tool, we examined control participants (N=24) and patients (N=9) suffering from mild cognitive impairment or AD. They were examined with structural MRI and neuropsychology as well. Spearman’s rho was used to test correlation between the neuropsychology, cortical volumes derived from MRI and precognize data.ResultSignificant difference was found between disease duration and ACE subscores (visuospatial χ2=28,36 p<0,001; memory f=12,05 p<0,001). Visuospatial score showed strong negative correlation with disease duration (r:‐0.73; p<0.001). We also found significant difference in mouse movements between the control and affected group (p=0,019). Prominent correlation was presented between ACE visuospatial subscores and mousemove parameters (r= ‐0,39 p=0,037). Furthermore, significant negative correlation was demonstrated between precognize results and the cortical volume of both hemispheres (p=0,006; r= ‐0,59).ConclusionTesting of visuospatial abilities might hold important screening potential in the early identification of cognitive decline. Electronic algorithms could be able to test large populations without the mandatory need for qualified stuff and prominent financial background. Our test battery seems promising in the screening of dementia since the extracted data correlate well with the results of neuropsychology and structural neuroimaging.
Total sugar intake and cognition in community‐dwelling older adults
Authors: Ford Christopher N , Agarwal Puja , Beck Todd , Evans Denis A , Bennett David A 
Published: December 2021

AbstractBackgroundImpaired glucose metabolism has been implicated in the progression of Alzheimer’s disease. Data from the Rush Memory and Aging Project was used to examine the relationship between sugar intake and cognition.MethodData were included from 837 respondents in the Rush Memory and Aging Project with complete food frequency questionnaire data consisting of 144 items. Cognition was assessed using a battery of 19 cognitive tests. Missing data were imputed using multiple imputation with chained equations. Linear random effects regression models were used to examine the relationship between total calorie‐adjusted quintile of sugar intake and global cognition, working memory, semantic memory, episodic memory, perceptual orientation and perceptual speed. Linear random effect models included race/ethnicity, age, sex, and time interactions for education (years), total energy (kilocalories/day), alcohol intake (grams/week), high‐density lipoprotein cholesterol (HDL‐C) and a continuous base term for time. Cox proportional hazards models were used to examine the relationship between total sugar intake and hazard of Alzheimer’s dementia, and to explore potential effect measure modification and confounding by race/ethnicity, age, sex, HDL‐C, total energy, alcohol intake, education and history of diabetes and hypertension. Variables were considered confounders if their inclusion resulted in >10% change in the crude hazard ratio. Effect measure modification was examined by including a time interaction term in Cox models and a performing a Wald test.ResultIn adjusted linear random effect models (Table 1) continuous quintile of sugar intake was inversely related to global cognition (β=‐0.0073; SE=0.0019; p=<0.001), episodic memory (β=‐0.0078; SE=0.0026; p=0.0026), semantic memory (β=‐0.0096; SE=0.0023; p=<0.001), working memory (β=‐0.0056; SE=0.0023; p=0.015) and perceptual speed (β=‐0.0090; SE=0.0025; p<0.001). There were 200 cases of Alzheimer’s dementia over 5,098 person years of follow‐up (IR: 39.2 cases per 1,000 person‐years). In crude Cox proportional hazards models (Table 2), those in the fifth quintile of total sugar intake were 1.84 (95% CI: 1.18; 2.87) as likely to develop Alzheimer’s dementia as those in the first quintile. A significant linear trend relationship was observed (p=0.006).ConclusionThere is some evidence to suggest that total sugar intake may adversely affect cognitive function over time, and it may increase risk of Alzheimer’s dementia.
Populacional epidemiological study of dementia in the city of Londrina, Paraná, Brazil
Authors: Nakakogue Lindsey Mitie , Bersi Lília Maria Machado , Lepre Rafael Perusso 
Published: December 2021

AbstractBackgroundUnderstanding the population context of dementias allows us to prepare socio‐economic and public policies aimed at broad and early care of the elderly population, in order to enhance health care, concerning the prevention and treatment of these diseases. The objective of the study is to obtain an estimate of the prevalence of dementia in Londrina ‐ PR, through the sample of two specialized service centers, as well as qualitative analysis of variants, such as subtype of dementias, gender, age, education, comorbidities, life habits, degree of dementia (CDR) and drugs used for its treatment, with the purpose of correlating them to gather information on potential risk factors for the development of dementia and, therefore, to be able to perform early diagnoses and proper interventions.MethodA collection of 1469 electronic medical records were undertaken and analyzed manually from patients who consulted with previous diagnosis or who were diagnosed with dementia in 2019. When the exclusion criteria were applied, a total of 658 patients remained.ResultThe prevalence found in the ambulatory clinics of PUC‐PR and in the Municipal Polyclinic of Londrina are, respectively, 11.18% and 60.80%. It was detected that 60.8% of the diagnoses were in the female sex, with only 39.2% in the male sex. And there was a peak of diagnoses in patients who were 80‐89 years old. It was also observed 82% of cases of Alzheimer's Disease (AD), 7.1% of Mixed Dementia (MD), 5.8% of Vascular Dementia (VD), 3.4% of Lewy's Body Dementia and 1.7% of Parkinson's Disease. No correlation of dependence was identified between the development of dementia and the level of education (p > 0.05). In comorbidities, previous strokes were a risk factor for AD, VD and MD. A higher CDR was observed in older age groups. Greater use of donepezil and memantine was observed in AD and greater use of galantamine in DV.ConclusionIt has been concluded that additional studies are needed to prove the potential risk factors for dementias, so that an early approach and prevention of this disease can be invested in, improving care even more.
Subjective cognitive and motoric complaints as predictors of motoric cognitive risk syndrome
Authors: Ayers Emmeline , Verghese Joe 
Published: December 2021

AbstractBackgroundMotoric cognitive risk syndrome (MCR) is a pre‐dementia syndrome characterized by the presence of slow gait and cognitive complaints in non‐demented patients. Self‐reported subjective cognitive complaints (SCCs) have been shown to be harbingers of future cognitive decline. Likewise, subjective motoric complaints (SMC) are common with aging, and predict risk for future gait decline. Subjective complaints might have utility in screening and remote assessments. Our objective was to examine the validity of a subjective definition of MCR (presence of subjective motoric AND cognitive complaints) for predicting incident MCR defined using objective gait speed.MethodsFive SMC and 8 SCC questions (independent of the SCCs used in the objective MCR definition) were assessed in a sample of 501 non‐demented community‐dwelling adults age 65 and older. Cox proportional hazard models adjusted for age, sex, education, comorbidities and a test of global cognitive function were used to examine the association between subjective MCR (presence of SMC and SCC) and risk of incident objective MCR (defined as slow gait 1 standard deviation below age and sex means and SCC).ResultsAt baseline, 360 participants (71.1%) reported one or more subjective motoric complaints and 368 (72.7%) reported one or more SCCs. Two‐hundred seventy‐nine participants (55.1%) reported the presence of one or more of both SMC and SCCs (subjective MCR). Participants with subjective MCR were older (77.9 vs. 74.9) and more often female (61.4% vs. 48.4%) than those without subjective MCR. Of the 501 participants, 38 developed objective MCR over a median follow‐up 2.5 years. Subjective MCR was associated with increased risk of developing objective MCR (adjusted hazard ratio (aHR): 3.88, 95% Confidence Interval (CI): 1.58‐9.51). When subjective MCR was defined as the presence of 2 or more SMC and SCC, the association with objective MCR was stronger (aHR: 4.78, 95% CI: 2.45‐9.33).ConclusionsSubjectively defined MCR is associated with increased risk of incident MCR. Remote identification of people at high‐risk for MCR has potential for clinical and research applications especially given the social isolation imposed by the Covid‐19 pandemic.
Racial differences in cognitive resilience to parental history of AD and cognitive impairment: The Offspring study
Authors: Manly Jennifer J , Avila Justina F , Vonk Jet MJ , Rentería Miguel Arce , Turney Indira C , Lao Patrick J , Seblova Dominika , Martinez Michelle N , Gutierrez Jose , Mayeux Richard , Schupf Nicole , Brickman Adam M 
Published: December 2021

AbstractBackgroundThe effect of family history on risk of developing late‐onset AD differs across race/ethnicity; however, the mechanisms underlying AD risk or resilience through heritability of genetic, environmental, and health factors are not well understood. Few large‐scale cohort studies have prospectively‐collected data of both parental and offspring generations and most intergenerational AD research is performed among volunteer‐based, well‐educated, White parents and offspring. We examined whether the association of midlife cognitive function with parental dementia status differs across race and ethnicity.MethodCognitive function was assessed in non‐Latinx White (n=66), non‐Latinx Black (n=181), Latinx English speaking (n=224), and Latinx Spanish speaking (n=362) people age 27 to 91 (mean age=56.5). Participants were offspring of participants in WHICAP, a community‐based sample of Medicare‐eligible residents of Washington Heights aged 65 and older. Of the 833 offspring, 610 families were represented, of which 176 (29%) parents were demented. We examined the association of parental dementia status on offspring measures of memory, attention, working memory, fluency, and processing speed, after adjusting for offspring age, sex/gender, parental education, and family relatedness, and tested for interactions between parental dementia status and racial/ethnic group. Next, we used multiple‐group analyses determined whether parental baseline memory performance predicted offspring cognitive test scores, adjusting for covariates.ResultOffspring of WHICAP parents with dementia obtained lower scores on measures of memory, working memory, and attention, but processing speed and language were not affected by parental dementia status. Overall, offspring whose parents had poor memory had lower cognitive function across multiple domains (Figure 1); however, parental memory had a stronger impact on offspring memory, working memory, and fluency in non‐Latinx White and English speaking Latinx participants, compared with non‐Latinx Black and Spanish speaking Latinx participants.ConclusionThis intergenerational study demonstrated that in middle age, offspring of parents with dementia have poorer cognitive function than offspring of parents without dementia, independent of parental SES; however, the strength of this relationship differed by race, ethnicity, and language. Results suggest that social and biological variables that confer familial risk and resilience may differ based on contextual factors that are patterned by racial and linguistic background.
The influence of race on intraprocedural complication and side effect rates of lumbar punctures
Authors: Eierman Allison C. , Cole Aleshia , Van Hulle Carol A. , Ma Yue , Lazar Karen K. , Carlsson Cynthia M. , Chin Nathaniel A. , Asthana Sanjay , Blazel Hanna , Bendlin Barbara B. , Okonkwo Ozioma C. , Edwards Dorothy Farrar , Wahoske Michelle L. , Johnson Sterling C. , Gleason Carey E. 
Published: December 2021

AbstractBackgroundA lumbar puncture (LP) is required to study cerebrospinal fluid (CSF) based biomarkers in preclinical Alzheimer’s Disease (AD). However, participants are often reluctant to undergo an LP due to fear. Insufficient data on the experiences of participants from underrepresented groups may contribute to their greater reluctance to agree to LP procedures, impacting diversity in AD studies. This analysis explores racial differences in intra‐procedural and post‐procedural complications rates.Methods870 LP procedures were performed on 606 participants in the Wisconsin Alzheimer's Disease Research Center, using a standardized technique with 24 or 25 gauge atraumatic needles. Up to 22 milliliters of CSF was obtained using gentle syringe aspiration of fluid. The clinician performing the procedure documented any intraprocedural complications experienced, including: headache, pain, vasovagal response, and radiculopathy. A follow‐up phone call the next day was used to assess any side effects following the procedure. Statistical analysis was performed using IBM‐SPSS version 27. Chi‐square tests were performed to compare complication rates between non‐Hispanic white, African American, and American Indian participants. Logistic regression analysis helped determine if BMI and waist‐to‐hip ratio also influenced complication rates.ResultsSample characteristics are shown in Table 1. LP success rates varied significantly by race (11.370, p=0.001). 90% of White, 77.5% of African American, and 66.6% of American Indian participants had a successful LP (Table 2); 61.1% of White, 48.8% of African American, and 52.4% of American Indian participants experienced zero complications (Figure 1). African American and American Indian participants experienced higher rates of total intraprocedural complications (9.642, p=0.022; 0.975, p=0.807 respectively). There was a significant group difference in reports of pain and headache during the procedure. However, few participants experienced any post‐procedural side effects. Overall, 5.5% experienced a headache and 8.5% experienced low back pain and no significant differences were seen between racial groups.ConclusionLPs are relatively safe with limited intraprocedural complications and few post‐procedural side effects. These results can help re‐evaluate potential disparities, alter LP procedures, and provide accurate information to potential participants to increase recruitment and study diversity.
Sex differences in the association between smoking status and increased incidence of Alzheimer’s dementia
Authors: Aslanyan Vahan , Ortega Nancy E , Mack Wendy J , Pa Judy 
Published: December 2021

AbstractBackgroundGrowing evidence indicates that smoking, a late life risk factor for Alzheimer’s dementia (AD), is significantly associated with increased prevalence of AD. However, the relationship between sex, smoking, and incident AD has not been well explored. The current study examined the relationship between sex, smoking status, and time to clinical diagnosis of AD.Method387 participants from UK Biobank were included in the study (mean±SE age=67.7±1.5 years, 50.9% female). Participants were over the age of 65 at their baseline visit and subsequently developed AD. Participant smoking status was determined from a baseline lifestyle questionnaire (8.5% current smoker, 45.7% previous smoker). Cox proportional‐hazard models were used to test the association between smoking and conversion. An interaction term and stratification by sex were used to assess the moderating role of sex in the association. Baseline age, APOE‐e4 status, sex, and Townsend deprivation index were included in the analyses.ResultMedian time to conversion was 6.39 years (interquartile range (IQR): 2.75) among never‐smoker participants, 6.36 years (IQR: 2.5) among previous smokers, while current smokers had a median time to conversion of 5.56 years (IQR: 2.59). Never‐smoker men had a shorter median time to conversion than never‐smoker women (6.20 (2.55) vs 6.57 (2.96) years). Current smoker men had a shorter median time to conversion than current smoker women (5.41 (2.69) vs 5.81 (1.87)). Previous smoker men, however, had a longer median time to conversion than previous smoker women (6.47 (2.46) vs 6.0 (2.58)). The hazard ratio (HR) for the current smokers relative to never‐smokers was 1.52 (confidence interval (CI): (1.03, 2.24), p=0.04), indicating that smoking increases the risk of conversion to AD by 52%. Smoking status and sex interaction (HR=0.65, CI: (0.42,0.99), p=0.05) revealed a significant difference between previous smoker men (HR=0.73, CI: (0.53,1), p=0.06) and previous smoker women (HR=1.11, CI: (0.83,1.5), p=0.48). Cessation of smoking had an opposing effect on the relative risk between men (reduced by 27%) and women (increased by 11%).ConclusionCurrent smoking status is associated with increased incidence of AD and differs by sex. Further analyses are needed to understand the causal mechanisms by sex underlying these associations.
Sex differences in survival in younger‐onset dementia
Authors: Loi Samantha M , Tsoukra Paraskevi , Chen Ben , Wibawa Pierre , Eratne Dhamidhu , Kelso Wendy , Farrand Sarah , Goh Anita M Y , Walterfang Mark , Velakoulis Dennis 
Published: December 2021

AbstractBackgroundThere is limited information about survival and mortality in younger‐onset dementia (YOD), including the role of sex differences. In older‐onset Alzheimer’s disease (AD), the risk of AD appears to be higher in women, despite longer life expectancy, and a recent mortality study suggested that women’s older age at death may explain sex‐related differences in death rates from AD and dementia (1). There have also been reports that women have more atrophy and amyloid burden in YOD (2). We sought to further explore this in YOD.MethodNeuropsychiatry inpatients with a diagnosis of dementia or cognitive impairment (excluding those who had a diagnosis of Huntington’s disease) between 1992‐2014 were submitted to the Australian National Death Index. Kaplan Meier curves were used to estimate median survival and standardized mortality ratios (SMRs) were used to compare deaths in people with YOD with population norms.Results468 inpatients were included in the study, of whom n=330 of them (74.5%) had a YOD. 65% of them (n=215) had died. The mean age of death was 64 years old (SD=10.4). Median survival for the different dementias were: AD – 11.2 years, frontotemporal dementia (FTD) – 10.7 years, “other dementia” – 14.8 years and vascular dementia – 12.3 years. There were no differences in the proportions of people who had died according to dementia type, p=0.438 but median survival for men and women was significant, with men – 13.6 years, compared to women 10.9 years, p=0.02. SMRs were also higher for FTD (SMR=8.1) and for women, compared to men, particularly with women+FTD (SMR=12.2).ConclusionThis study highlights that sex differences also exist in YOD. Differences such as increased cognitive reserve in men and sex‐related bias in identifying dementia in younger people are possible explanations but further investigation is warranted.References: 1. Buckley R. et al. 2019. To what extent does age at death account for sex differences in rates of mortality from AD? Am J Epidemiology. 188: 1213‐1223. 2. Groh J. et al. 2020. Sex‐associated differences in pathology burden in early‐onset AD. Alzheimer’s Dement. 16 (supp. 5): e046532