bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep duration and its association with cognition vary with rurality in older veterans
Authors: Silbert Lisa C , Wall Rachel C , Beattie Zachary , Dodge Hiroko H , Mattek Nora , Riley Thomas , Lim Miranda , Kaye Jeffrey
Published: December 2020

Background

Sleep duration is associated with cognitive health in older individuals and is increasingly recognized as an important modifiable factor related to dementia risk. Sleep and its relationship with cognitive function is understudied in rural U.S. Veterans, who are under‐represented in clinical research aging studies.

Method

Participants (age > 57) were enrolled as part of Collaborative Aging Research using Technology (CART), a multi‐site study examining the feasibility of unobtrusive remote sensing and monitoring of physical, cognitive, behavioral, physiological, and health‐related activities. The VA cohort consists of volunteers living in largely rural communities in the Pacific Northwest, self‐identified as being a Veteran, and included their cohabitant, if applicable. Nightly hours of sleep were estimated using a wrist worn device and baseline one month averages were compared with rural status and cognitive function.

Result

114 nondemented participants from 67 homes underwent neuropsychological testing and passive monitoring of daily activities (55% male, age 70.7, MOCA 23.4). 70% resided in a rural area, defined as having a rural‐urban commuting area (RUCA) score of 4 or higher (30% urban, 28% large‐rural, 34% small‐isolated‐rural). Participants with 7+ days of recorded sleep measured within a one‐month period near baseline cognitive assessments were included in the analysis (n = 99). Mean hours of sleep obtained over an average of 24.4 days was 7.8 hours (SD 1.7). Participants living in urban areas slept less (7.3 hrs) than those living in large‐rural (8.3 hrs) but not small‐isolated rural areas (7.6 hrs)(p<0.05). Poorer executive function and global cognition were related to decreased sleep duration in Veterans living in small‐isolated and large rural areas, respectively.

Conclusion

In a cohort comprised of mostly rural Veteran’s and their spouses, living just outside of an urban area was associated with longer sleep duration. However, this relationship did not exist in Veterans living in smaller rural centers. Sleep duration was associated with poorer cognition in rural, not urban, Veterans. Passive, in‐home monitoring can provide objective measures of sleep activity that may serve as a sensitive index of dementia risk and as a tool to investigate sleep dysfunction and its relationship with cognitive health in older rural Veterans.
Polygenic hazard scores in superagers: Supergenes or superresilience?
Authors: Spencer Barbara E. , Banks Sarah Jane , Dale Anders M. , Brewer James B. , Makowski‐Woidan Beth , Weintraub Sandra , Mesulam Marsel , Geula Changiz , Rogalski Emily J.
Published: December 2020

Background

Unusually successful cognitive aging (e.g. SuperAging) may reflect underlying resistance to age‐associated cognitive decline and the neuropathologic markers of Alzheimer’s disease (AD). However, it is unknown whether these individuals vary in their genetic protection from AD relative to other clinically normal elderly individuals.

Method

The Northwestern SuperAgers cohort (n=41) was limited to clinically normal individuals who were at least 80 years old but performed at or above normative values for average 50 to 65‐year‐olds on delayed recall of the Rey Auditory Verbal Learning Test and within one standard deviation of the average normative range for their age, or better, on non‐episodic memory tests including the 30‐item Boston Naming Test, Trail Making Test Part‐B and Category Fluency Test (Animals). The UC San Diego (UCSD) Shiley Marcos Alzheimer’s Disease Research Center and Alzheimer’s Disease Neuroimaging Initiative (ADNI) comparison cohorts (n=17 and 46, respectively) included all clinically normal individuals with available genetic data who were at least 80 years old but did not meet the criteria for SuperAgers outlined above. Polygenic hazard scores (PHS) were downloaded from ADNI and calculated for each participant as described (Desikan et al., 2017) for the Northwestern and UCSD cohorts. Briefly, the PHS combines an individual’s genotype for 31 AD‐associated SNPs in addition to APOE.

Result

All three cohorts were similar in age (range: 80‐101) and years of education (range: 12‐20). However, there were significantly more women in the Northwestern SuperAgers cohort (p < 0.001). The mean PHS in each cohort was negative, indicating that these individuals had less than average population risk for AD. However, there were no significant differences in PHS between cohorts.

Conclusion

As a group, SuperAgers did not have lower polygenic risk for AD than clinically normal elderly individuals, suggesting determinants of superior memory performance in older age cannot be solely explained by having unusually low risk for AD as assessed by common genetic variants. Given the sex differences in these cohorts, future work should consider whether sex‐specific polygenic risk for AD contributes to the superior memory performance of SuperAgers.
Does feeding route affect advanced dementia patients’ caregiver burden?
Authors: Cintra Marco Túlio , Bicalho Maria Aparecida , Torres Henrique Gama , Rezende Nilton Alves
Published: December 2020

Background

Indication for alternative feeding route (enteral nutrition ‐ EN) in elderly patients with advanced dementia remains controversial, especially when considering caregiver burden. The objective of this work was to evaluate caregiver burden of patients with advanced dementia with moderate to severe oropharyngeal dysphagia.

Method

A cohort of 67 patients with advanced dementia, 31 on EN and 36 on oral feeding (OF), was followed for a minimum period of 6 months. The Zarit Caregiver Overload Scale was applied to caregivers on admission (D0) and 90 (D90) and 180 days (D180) after recruitment. T student test for paired samples, T student test for independent samples, linear regression logistics, Pearson correlation coefficient and multivariate analysis were employed to compare samples and to disclose independent variables related to caregiver burden. SPSS 19.0 and Stata10.0 were employed.

Result

Sociodemographic and clinical variables were similar between the groups. Analyzing overall sample showed caregiver burden reduction from 28.72 (D0) to 25.95 (D90) and 22.89 (D180) points of Zarit Scale, with a p‐value of 0.001 between D0 and D180 and, p=0.020 between D90 and D180. In OF group, the overload was reduced from 30 to 26.79 after 90 days (p = 0.134) and to 24.29 after 180 days (p = 0.002). Statistical significance was also observed between D90 and D180 (p = 0.029). Overload reduced from 27.04 to 23.82 from D0 to D90 and to 18.71 on D180 in EN group, without reaching statistical significance. There were no statistical differences between OF and EN groups in any time. Deaths reduced importantly sample size in EN group (n = 11, D90 and n = 7, D180). After logistic regression analysis, inverse association between Zarit Scale on D0 and family income was observed, at the limit of statistical significance (p = 0.048 and r2 = 0.048).

Conclusion

There were no difference between OF and EN groups in overall caregiver burden along six months of follow up. However, significant reduction was observed in caregiver overload in OF group after 90 and 180 days of follow‐up. Also, there may be an inverse association between income and overload at recruitment.
Non‐demented elderly Latinos structurally and demographically matched to non‐Latino whites perform worse on visuo‐executive cognitive tests
Authors: Smirnov Denis S. , Galasko Doug R. , Brewer James B. , Edland Steven D. , Salmon David P.
Published: December 2020

Background

Previous work has shown that Latinos show a weaker relationship between cortical thickness and cognition in non‐demented elderly, potentially due to non‐neurodegenerative contributions. Here we examine if demographically and structurally matched Latino and Non‐Latino elderly differ in their cognitive performance and vascular risk.

Methods

Both Latino and Non‐Latino White (NLW) elderly non‐demented participants underwent structural MRI and cognitive assessment at the Shiley‐Marcos UCSD ADRC. To examine the impact of being Latino on cognitive performance when matched structurally, we took a causal inference approach by propensity score matching Latino participants in a 1:3 ratio to NLW participants on age, sex, education, and bilateral cortical thicknesses from 12 regions affected by AD (“signature”): entorhinal, parahippocampal, inferior parietal, pars opercularis, orbitalis, and triangularis, inferior temporal, temporal pole, precuneus, supramarginal, superior parietal, and superior frontal. The sample Average Treatment effects on the Treated (ATT, i.e. the causal effect of being Latino) was calculated using simulation, adjusting for the same demographics and average thickness of the “signature” regions. A 7‐point vascular risk scale was generated from history of hypertension, hypercholesterolemia, TIA/stroke, diabetes, atrial fibrillation, cardiovascular disease, and current smoking status.

Results

The 26 Latino participants did not differ from their 78 demographically and structurally matched NLW participants on age, education, MMSE, functional impairment (POD), or cortical thickness is any of the selected regions (Table 1). However, Latino participants were more likely to have cardiovascular disease (p=0.047), and averaged 0.5 points higher on the vascular risk scale (p=0.027). The ATT of Latino on cognitive performance (Table 2) was significant for Visual Reproduction Copy [95% CI: ‐.87, ‐.31], Wisconsin Card Sorting Test categories [‐.65, ‐.13] and perseverative errors [.29, 1.28], Digit Span [‐4.00, ‐2.25], Block Design [‐9.02, ‐4.55], and Trails A [2.52, 7.72] and B [23.4, 40.6].

Conclusions

Demographically and structurally matched non‐demented Latino and Non‐Latino participants exhibited comparable general cognitive performance, as well as performance on tests of memory and language. However, Latino participants had significantly lower scores on a broad range of visuospatial and executive tests. We hypothesize that this may be related to the increased vascular risk in the matched Latino group.
Hippocampal volume loss is associated with PET amyloid deposition in nondemented elderly individuals
Authors: Sathishkumar Mithra , Larson Myra S. , Taylor Lisa , Keator David , Hollearn Martina K. , Miranda Blake A. , Tustison Nick , McMillan Liv , Gillen Daniel L. , Yassa Michael A.
Published: December 2020

Background

Amyloid‐beta (Aβ) plaques are among the hallmark pathologies of Alzheimer’s disease (AD) and could potentially influence the aggregation of tau pathology, which is associated with neurodegeneration in AD. Prior work has demonstrated that left hippocampal atrophy is present in both Alzheimer’s disease (AD) and mild cognitive impairment (MCI). However, these relationships are not clear in preclinical AD (i.e. those with Aβ biomarkers but no clinical impairment). This study assesses the relationship between Aβ pathology and hippocampal volume in nondemented older adults without clinical impairment.

Method

Data from 54 adults (60‐85 years of age, 41 female) enrolled in the Biomarker Exploration for Aging, Cognition, and Neurodegeneration (BEACoN) study were included in this analysis. Participants underwent T1‐weighted MRI scans (MPRAGE) and PET amyloid scans with F18‐florbetapir (AV‐45) at the University of California, Irvine. Aβ status (+ or ‐) was determined by the composite score defined by Jack et al (Alz Dem 2017). Each subject’s T1 weighted MRI image was skull stripped and run through the joint label fusion (JLF) pipeline in ANTs to obtain medial temporal lobe subregion volumes and surface area. Cortical reconstruction was performed using Freesurfer 6.0 to obtain estimated total intracranial volume (ICV). All scans were then subjected to visual QC to ensure high quality segmentations. Of the sample of 54, 39 (29F) were Aβ‐ and 15 (12F) were Aβ+. We used two multiple regressions to determine if Aβ status was associated with left hippocampal volume. The first treated Aβ status as a binary variable and the second used the continuous SUVR measure in the AD composite region. Both models accounted for the effect of age and gender.

Result

We found a significant association between left hippocampal volume and Aβ status, which remained significant after adjusting for age and gender. The result was further corroborated by using the continuous SUVR measures.

Conclusion

Our results suggest that the association between amyloid deposition and hippocampal atrophy may begin years before the onset of Alzheimer’s disease and can be detected even in nondemented older adults. Future work is needed to examine whether these relationships change longitudinally.
Alzheimer’s disease: Blood serum circulating microRNAs as diagnostic biomarkers
Authors: Giles Abdul‐Mannaan
Published: December 2020

Background

Alzheimer’s disease (AD) is the most common age‐related dementia. One of its biggest challenges is identifying signature molecular expressions that would detect it before the clinical symptoms manifest. With advances in technology related to next generation sequencing (NGS) of microRNAs, several avenues are being explored that may enable the identification of a unique diagnostic marker for early‐stage AD

Method

The main goal was to investigate the expression of a select group of miRNAs circulating in blood serum of AD patients in search of diagnostic markers for Alzheimer’s disease. Two select blood plasma miRNAs were profiled using miRCURY LNA miRNA qPCR serum array on five AD samples.

Result

Results showed that the two target sequences hsa‐miR‐181b‐3p and hsa‐miR‐21p were present in the AD samples with an increased adjusted expression (miR‐181b Ct = 29 and miR‐21p Ct = 27 respectively) compared to normal controls (xCt = 31).

Conclusion

These outcomes suggest that aberrant expression of plasma miRNA has potential to be used to assess AD and that next generation sequencing technologies can be used as a viable tool for enhancing AD diagnosis.
Blood‐brain barrier permeability measured by 7α‐hydroxy‐3‐oxo‐4‐cholestenoic acid in CSF associates with Alzheimer’s pathology biomarkers in cerebrospinal fluid
Authors: Heston Margo B. , Vogt Nicholas M. , Kohli Akshay , Sun Yi , Kerby Robert L. , Carlsson Cynthia M. , Engelman Corinne D. , Johnson Sterling C. , Asthana Sanjay , Ulland Tyler , Blennow Kaj , Zetterberg Henrik , Rey Federico E. , Bendlin Barbara B.
Published: December 2020

Background

The intestinal microbiota may modulate Alzheimer’s disease (AD), however the mechanisms by which it impacts the brain remain unknown. A leading proposal suggests that altered gut permeability promotes systemic inflammation, which may impact blood‐brain barrier (BBB) and exacerbate AD pathology. To test this hypothesis, we performed analyses on levels of 7α‐hydroxy‐3‐oxo‐4‐cholestenoic acid (7‐HOCA), a potential BBB permeability marker, calprotectin in stool, a gastrointestinal inflammation marker, and cerebrospinal fluid biomarkers of AD pathology. We tested for differences in BBB by cognitive diagnosis, associations with AD biomarkers in CSF, and potential mediation by calprotectin.

Method

CSF was collected via lumbar puncture from participants in the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center [CU (N=334), AD mild cognitive impairment (MCI) (N=35), AD dementia (N=40)]. Stool samples from 25 of these participants [CU (N=16), AD (N=9)] were additionally analyzed for calprotectin levels (ELISA, Eagle Biosciences). 7‐HOCA relative abundance in CSF and plasma was measured via Metabolon’s UHPLC/MS metabolomics platform. CSF biomarkers included Aβ42/Aβ40, NfL, pTau, tTau, YKL‐40 and neurogranin. Multiple linear regressions (R) were performed across 7‐HOCA, calprotectin and AD biomarkers controlling for age, sex and APOE ε4 carrier status.

Result

7‐HOCA levels in CSF were significantly increased in AD compared with CU participants (Figure 1). pTau/Aβ42 was significantly negatively associated with 7‐HOCA (Figure 2), while pTau, tTau, YKL‐40, NfL, and neurogranin were significantly positively associated with 7‐HOCA levels. Aβ42/Aβ40 was not associated with 7‐HOCA. Elevated calprotectin associated with CSF amyloid positivity (Figure 3), but due to small sample size this did not meet statistical significance. No significant associations were found with plasma 7‐HOCA, or with calprotectin moderating the biomarker/7‐HOCA relationships.

Conclusion

7‐HOCA is elevated in AD dementia, and is associated with markers of AD, neurodegeneration, and glia activation measured in CSF, potentially suggesting altered BBB in AD. While model coefficients suggest relationships between AD biomarkers and the calprotectin*7‐HOCA interaction term, the results were not significant, likely due to the small N for calprotectin analyses. Additional analyses are needed to determine whether the effects of gut microbiota on brain may be mediated by altered intestinal and BBB permeability.
Lipid metabolism dysfunction in progranulin mutation carriers: Unbiased metabolomics reveals strong relationship to clinical status in FTLD
Authors: Vandevrede Lawren , Rojas Julio C. , Wang Ping , Heuer Hilary W. , Karydas Anna M. , Ljubenkov Peter A. , Boeve Bradley F. , Rosen Howard J. , Boxer Adam L. ,   ARTFL and LEFFTDS Consortia Investigators
Published: December 2020

Background

Heterozygous progranulin (GRN) mutations are an important cause of familial Frontotemporal Lobar Degeneration (f‐FTLD) associated with TDP‐43 pathology. The cellular role of progranulin remains unclear, but alterations in lipid metabolism and lysosomal function have been suggested. Better understanding the pathophysiology of progranulin deficiency is critical as several clinical trials are underway in this population, and fluid biomarkers are urgently needed to assess pharmacodynamic effects. Therefore, we conducted an unbiased metabolomic analysis in GRN mutation carriers and family member controls, and identified at least two classes of lipids altered in symptomatic GRN carriers.

Methods

Matched plasma and CSF samples were obtained from GRN mutation carriers (46 plasma, 36 CSF) and age‐matched blood relatives (36 plasma, 18 CSF). Untargeted metabolite detection was conducted via LC‐MS/MS in both plasma (1389 compounds) and CSF (508 compounds) by Metabolon. To identify important compounds in differentiating these groups, we conducted an unbiased analysis between family controls, asymptomatic carriers, and symptomatic carriers using univariate one‐way ANOVA with post‐hoc Fisher’s LSD corrected for false discovery rate (FDR) and partial least squares ‐ discriminant analysis (PLS‐DA, Metaboanalyst). For compounds identified by this unbiased approach, correlation with measures of disease severity was analyzed via linear regression, controlling for age and gender.

Results

In plasma, 22 compounds were identified as significant in discriminating between groups via ANOVA (FDR<0.05), and 17/22 were also identified by PLS‐DA (VIP>2.4). Of these, 21/22 compounds were lipids; 11 were sphingomyelins. Comparatively, in the relatively lipid‐poor CSF samples, 6/15 compounds identified by PLS‐DA (VIP>2.0) were phosphatidylcholines. Pathway impact analysis revealed a large impact from the GRN mutation on sphingolipids in plasma and glycerophospholipids in CSF. In secondary analyses, sphingomyelins were elevated in plasma from symptomatic carriers, while phosphatidylcholines were decreased in CSF. Secondary analyses showed these compounds were correlated with clinical measures of disease severity, including MoCA and CDR+NACC‐FTLD.

Conclusion

Increased plasma concentration of sphingomyelin and decreased CSF phosphatidylcholines are both associated with worse clinical status in FTLD‐GRN. These findings suggest that impaired lipid metabolism could play a pathogenic role in FTLD‐GRN. Targeted lipidomic measures in plasma and CSF may potentially reveal useful clinical trial biomarkers.
Quantifying acute tau inoculations in living rats using PET
Authors: Kunach Peter
Published: December 2020

Background

Monitoring tau propagation in the living brain has important pathophysiological and therapeutic implications. Previous studies assessing tau propagation relied on cross‐sectional immunohistochemical techniques in post‐mortem tissue, as such little is known regarding the behaviour of tau preparations in living systems. As tau imaging agents are dependent on tau conformations, we aim to determine the tau species amenable to in vivo imaging. As such, the goal of this work is to examine the binding properties of [18F]MK‐6240, a second‐generation tau imaging agent in different tau preparations.

Method

Seven Fisher 344 rats (15± 0.25 months) were used. All animal had a baseline scan with [18F]MK6240 before the stereotaxic tau injections. We tested various recombinant human tau PFFs and patient derived AD‐tau following gel extraction or serial filtration extraction. All tau preparations were stereotaxically injected in the dorsal hippocampus (DV: ‐3.5; AP: ‐3.5; ML:‐2). All recombinant tau PFFs had an injection volume of 2uL and concentration of 4ug/uL, whereas AD‐tau had an injection volume of 2uL and a concentration of 0.4 ug/uL. Structural MRI were conducted following surgery to determine the final position of the injection site. All animals underwent to a 1 hour dynamic acquisition PET with [18F]MK6240. The non‐displaceable binding potential (BPND) images were generated using cerebellar grey as a reference region based on Simplified Reference Tissue Method (SRTM). The comparison of the images was conducted using z‐scores.

Result

We injected a total of 7 rats with varying tau extracts. We found that the hemispheres injected with human tau extracts from both filtration and gel electrophoresis preparation method showed positive BPnd signals versus hemispheres with control injections. Both recombinant human tau PFF’s lacking FTD‐mutations show positive [18F]MK‐6240. The entire procedure was well tolerated by the animals.

Conclusion

These results reveal that PET [18F]MK‐6240 constitutes a promising method for quantification of tau seeding and propagation in the rat brain. Not all tau preparations provide binding sites for [18F]MK6240 binding. Future longitudinal studies will reveal whether these techniques will be able to capture tau propagation.
Head injury at different ages and cognitive performance in a diverse cohort: Findings from the KHANDLE Study
Authors: Nuno Miriam , Gilsanz Paola , Glymour M. Maria , Mayeda Elizabeth Rose , Eng Chloe W. , Peterson Rachel , George Kristen M. , Mungas Dan M. , DeCarli Charles , Whitmer Rachel A.
Published: December 2020

Background

Evidence is limited on the impact of a head injury and the role of age at injury on different cognitive domains, particularly among in diverse cohorts.

Methods

The Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study examines cognitive aging across four racial/ethnic groups (29% White, 26% Black, 24% Asian, & 20% Latino). Head injury was determined by asking: “Have you ever had a head injury where you lost consciousness or for which you received medical care?” Age at first injury was grouped as 0‐15, 16‐29, 30‐64 and 65+ years. Education was coded as college graduate or more and less than college graduate. Z‐standardized measures of verbal episodic memory, semantic memory, and executive function were assess using the Spanish and English Neuropsychological Assessment Scales (SENAS). The association between head injury and cognitive domains were analyzed with adjustment for age, sex, race, and education using multivariable linear regression models.

Results

Among the analytic sample of 1,666 participants, 392 (22.9%) reported history of a head injury. Exposure to head injury was not associated with deficits in executive function (β=0.04, 95% CI: −0.05, 0.14), verbal episodic memory (β=‐0.09, 95% CI: −0.02, 0.10), or semantic memory (β=0.07, 95% CI: −0.02, 0.16). Among those reporting a head injury, 77.1% experienced one injury, 15.5% 2 injuries, 4.6% 3 injuries, and 6.7% participants reported 4+ injuries. The median (interquartile range) age at first head injury was 24 (13‐60) years, and time since first head injury was 48 (14‐61) years. Age at first head injury was not associated with cognitive function when compared to individuals without a head injury (Table 1A). Among those with a history of head injury, age at first injury was not associated with executive function (65+ vs. 0‐15 years: β=‐0.25, 95% CI: −0.50, 0.01), verbal episodic memory (65+ vs. 0‐15 years: β=0.21, 95% CI: −0.05, 0.47), or semantic memory (65+ vs. 0‐15 years: β=‐0.09, 95% CI: −0.32, 0.13) (Table 1B).

Conclusion

Participants who reported a head injury did not exhibit worse cognition compared to those without history of injury nor was age at first head injury associated with any cognitive domain.
Heart failure with preserved ejection fraction (HFpEF) is associated with cognitive impairment and reduced brain volume
Authors: Hugenschmidt Christina E. , Hughes Timothy M. , Jung Youngkyoo , Lockhart Samuel N. , Whitlow Christopher T. , Yang Mia , Williams Benjamin J. , Cleveland Maryjo , Bateman James R. , Baker Laura D. , Sachs Bonnie C. , Craft Suzanne , Kitzman Dalane
Published: December 2020

Background

Increasingly, vascular diseases are implicated in risk for Alzheimer’s disease and related dementias. Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF in the U.S and most commonly affects older women with overweight/obesity. Given known systemic microvascular effects of HFpEF, dementia risk may be a potential unrecognized downstream effect of the disease.

Method

Harmonized cognitive testing and brain MRI protocols were employed in Wake Forest’s Alzheimer’s Disease Research Center’s Clinical Core and the SECRET‐2 clinical trial of HFpEF. Cognitive tests included components of NACC’s Uniform Data Set version 3. Brain imaging protocols included structural MRI and cerebral blood flow images. Statistical comparisons of cognitive and imaging data by cognitive/group status were done using multivariable general linear models adjusting for basic covariates including age, race, and sex in basic models and additional adjustments for intracranial volume (for MRI) and education (for cognitive test scores) in fully adjusted models using SAS 9.4.

Result

The analysis includes a comparison of 89 participants recruited into the Wake Forest ADRC (adjudicated as cognitively normal, n=43; MCI, n=22; and dementia, n=5) and SECTRET‐2 intervention trail in HFpEF (n=19) patients. Compared to cognitively normal participants, patients with HFpEF were significantly more likely to be Black (47% vs 2%, p<0.01), have a higher body mass index (38.2 vs. 28.0, p<0.01), and a diagnosis of hypertension (84% vs 26%). Patients with HFpEF had poorer global cognitive performance [MoCA score, beta(SE)=‐1.76(0.77), p=0.02)], but no differences in Craft Story delayed recall in models adjusted for age, gender, race and education. HFpEF was also significantly associated with smaller gray matter volume [beta(SE)=‐20.7(11.6), p=<0.01)] at levels worse than MCI and dementia in models adjusted for age, gender, race and ICV. No initial differences were observed in resting cerebral blood flow or evoked cerebrovascular response due to hypercapnia.

Conclusion

HFpEF participants showed deficits in global cognitive function that were comparable to those with MCI, as well as global decreases in brain volume. Additional follow‐up of these participants with HFpEF will more deeply phenotype cognitive impairments by domain and adjudication criteria used for MCI and dementia.
Anterolateral entorhinal cortical thinning as a biomarker for Alzheimer’s disease in Down syndrome
Authors: Sathishkumar Mithra , Janecek John , Smith Anna , Phelan Michael , Tustison Nick , Keator David , Doran Eric , Hom Christy , Nguyen Dana , Petersen Melissa , Rosas H. Diana , Lai Florence , Brickman Adam M , Schupf Nicole , Silverman Wayne , Lott Ira T , O'Bryant Sid , Yassa Michael A.
Published: December 2020

Background

Virtually all adults with Down syndrome (DS) develop Alzheimer’s disease (AD) associated neuropathology by the age of 40 and the majority of them develop dementia by age 60. Atrophy of the anterolateral entorhinal cortex (aLEC) has been previously associated with cognitive decline. Here, we sought to determine whether aLEC thinning is associated with clinical impairment in older adults with DS as well as whether it is associated with blood neurofilament light chain (NfL), another biomarker of neurodegeneration in AD.

Method

103 older adults with DS enrolled in the Alzheimer’s Disease in Down Syndrome (ADDS) study were included in this analysis. Scans were classified into 3 groups based on consensus diagnosis: 14 (6F) possible/definite dementia (DEM), 19 (5F) mild cognitive impairment (MCI‐DS) and 70 (28F) cognitively stable (CS). Images were processed through the joint label fusion (JLF) pipeline in ANTs to obtain medial temporal lobe subregional volumes and thickness. Cortical reconstruction was performed using Freesurfer 6.0 to obtain total intracranial volume (ICV). We used a multiple linear regression model to fit left aLEC thickness using diagnostic group as the independent variable, correcting for age, gender, ICV and scan site differences. For a subset of these data (N = 89), plasma NfL was quantified using a Simoa platform and we and tested whether left aLEC thickness was associated with NfL.

Result

Cortical thickness in left aLEC was a significant predictor of clinical status. Thickness values were highest in the CS group, followed by MCI‐DS, followed by DEM. Groupwise differences were significant in DEM vs. CS and DEM vs. MCI‐DS comparisons. We also found a significant correlation between NfL and left aLEC thickness specifically in the DEM group. Finally, random forest classification showed that both NfL and left aLEC thickness were important features in predicting clinical diagnosis DEM vs MCI‐DS. Their estimates provided a diagnosis ROC curve with sensitivity of 0.79 and specificity of 0.92.

Conclusion

In older adults with DS, left aLEC cortical thickness atrophy may be a primary feature of structural neurodegeneration that is associated with MCI‐DS and a blood‐based measurement of NfL may be informative as to this structural degeneration.
Detecting amnestic MCI among persons with HIV with high rates of HIV‐associated neurocognitive disorder
Authors: Sundermann Erin E. , Bondi Mark W. , Umlauf Anya E. , Vaida Florin , Moore David J.
Published: December 2020

Background

HIV‐associated neurocognitive disorders (HAND) occur in ∼45% of people with HIV (PWH). Older PWH are at‐risk for both HAND and age‐associated disorders including Alzheimer’s disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). Distinguishing aMCI from HAND among PWH is a diagnostic challenge given that both aMCI and HAND criteria include memory deficits. Differences between aMCI and HAND may include a more amnestic (recall and recognition deficits) and degenerative profile in aMCI versus milder (recall but not recognition deficits) and typically stable memory deficits in HAND. We exploited these differences to classify PWH based on aMCI+/‐ and HAND+/‐ status and compared trajectories of learning, recall and recognition performance among these classification groups.

Method

Analyses included 685 PWH (ages 18‐79, 88% men) from the UCSD HIV Neurobehavioral Research Program. At baseline, aMCI status was determined based on a neuropsychological classification approach (Jak/Bondi) requiring impairment (<1.0 SD below normative mean) on two tests of recall and/or recognition (at‐least one recognition impairment required) from the Hopkins Verbal Learning Test‐Revised (HVLT‐R) and the Brief Visuospatial Memory Test‐R (BVMT‐R). HAND was diagnosed based on standard Frascati criteria. Using additive mixed model, trajectories of learning (averaged HVLT‐R and BVMT‐R learning scores), recall (averaged HVLT‐R and BVMT‐R recall scores) and HVLT‐R and BVMT‐R recognition z‐scores adjusted for age, sex, race and education were compared among classification groups.

Result

Participants were classified into four groups: aMCI‐/HAND‐ (n=243), aMCI‐/HAND+ (n=199), aMCI+/HAND‐ (n=62) and aMCI+/HAND+ (n=181). There were significant diagnostic group X time interactions on learning and HVLT‐R and BVMT‐R recognition, but not recall (Figure 1). Learning showed significant change over time in the aMCI+/HAND+ and aMCI‐/HAND+ groups only. All groups showed significant, yet variable, patterns of change in HVLT‐R recognition. BVMT‐R recognition showed significant change over time in aMCI+/HAND‐ and aMCI+/HAND+ groups. Recall was poorest in the aMCI+/HAND+ versus other groups across time.

Conclusion

Findings suggest that PWH with memory impairment combined with other cognitive deficits at baseline show the worst memory profiles over time. Research is needed into methods of differentiating other MCI subtypes from HAND and into potential compounding effects of AD‐ and HAND‐related pathologies.
AgeWell.de (Germany)
Authors: Roehr Susanne , Hoffmann Wolfgang , Thyrian Jochen René , Kaduszkiewicz Hanna , Frese Thomas , Gensichen Jochen , Haefeli Walter E. , Czock David , König Hans‐Helmut , Wiese Birgitt , Riedel‐Heller Steffi G.
Published: December 2020

Background

Based on the share of the population aged 65 years and older, Germany is among the world's oldest countries. Therefore, dementia prevention is a very important public health target. AgeWell.de is the first large‐scale multi‐component lifestyle intervention trial against cognitive decline in Germany. It has been designed with a specific focus on a pragmatic approach to allow easy translation into routine care.

Method

AgeWell.de is an ongoing multi‐centric, cluster‐randomized controlled multi‐component lifestyle intervention trial aiming at preventing or delaying cognitive decline. Participants are older community‐dwelling general practitioner (GP) patients (60–77 years; n > 1,000) with increased dementia risk according to the CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) dementia risk score. The multi‐component intervention A includes nutritional counseling, physical activity, cognitive training, optimization of medication, management of vascular risk factors, social activity, and, if necessary, further specific interventions targeting grief and depression. Intervention B includes general health advice regarding the intervention components and GP treatment as usual. The observation period is two years. Trained study nurses conduct structured interviews including a comprehensive neuropsychological test battery at baseline and follow‐ups, complemented by motivational telephone sessions with the intervention group.

Results

Recruitment and baseline assessments have been completed. Baseline characteristics of the study sample will be presented at AAIC.

Conclusion

AgeWell.de covers a broad set of lifestyle interventions. We therefore hope to add additional knowledge on how to effectively shape dementia prevention programs in the future.
MIND China (China)
Authors: Wang Yongxiang , Qiu Chengxuan , Cong Lin , Tang Shi , Hou Tingting , Liu Cuicui , Du Yifeng
Published: December 2020

Background

Epidemiologic studies have estimated that around one‐third of dementia patients worldwide might be attributable to seven modifiable risk factors. This implies that interventions to improve the control of modifiable risk factors may delay the onset of age‐related cognitive disorders such as dementia. We presented the study design and progress of the ongoing randomized controlled multimodal interventions to delay dementia and disability in rural China (MIND‐CHINA).

Methods

MIND‐CHINA is designed as a 2‐year cluster‐randomized, controlled, multimodal intervention study, which targets people who are aged 60‐79 years and living in the rural communities of Yanlou Town, western Shandong Province, China. Following the baseline examination, 52 villages in Yanlou Town are randomly (cluster‐randomization) divided into three groups: control group (regular primary health care service), vascular intervention group, and multimodal intervention group. The multimodal intervention program consists of four modules that are sensitive to Chinese lifestyle and sociocultural tradition; medical control of vascular risk factors; lifestyle and nutritional guidelines; group physical exercise and personalized leisure activities; and cognitive training.

Results

In March‐October 2018, we carried out baseline assessment for MIND‐CHINA that integrated our special examinations with the National Primary Health Care Services, during which 5764 persons were examined. We collected the following data through face‐to‐face interviews, clinical examination, testing, and laboratory tests: epidemiological, clinical, and biochemical data as well as physical function, cognitive function, mild cognitive impairment, and dementia. In May‐September 2019, the pilot study was completed to test the feasibility of the intervention programs and the implementation procedure in 7 villages (2 villages in control group, 3 villages in vascular intervention group, and 2 villages in multimodal intervention group). Recruitment of participants for interventions started in Oct/November 2019, and 2265 participants have been successfully recruited so far.

Conclusion

It is feasible to integrate a comprehensive health examination program with local primary health care services in rural‐dwelling elderly Chinese people. MIND‐CHINA will be likely to address whether multimodal interventions sensitive to Chinese lifestyle and socioculture help maintain cognitive and physical functioning among community‐dwelling elderly people in rural areas.
APOE4 carrier identification, genetic disclosure and amyloid status: Results from the generation 2 program Alzheimer's disease prevention clinical trial at Glasgow Memory Clinic
Authors: Lynch Jennifer , Hendry Kirsty , Lee Emma , Wallace Lorna , Williamson Susan , Main Laura , Cranmer Alison , Inglis Fraser
Published: December 2020

Background

Research has demonstrated that the APOE‐ε4 genotype is a genetic risk factor for Alzheimer’s Disease (AD) and individuals with this genotype are also at increased risk of having higher levels of β‐amyloid (Aβ); a neurochemical indicator of AD. [1]The Generation 2 Study, co‐sponsored by Novartis, Amgen and the Banner Alzheimer Institute, investigated the impact of experimental medications on Aβ levels and whether this can result in later onset of AD in those identified as having higher genetic risk. Here, we show the Generation 2 Study screening activity completed at Glasgow Memory Clinic until the early cessation of this clinical trial.

Method

To identify subjects with the APOE‐ε4 variant of this gene, a high‐volume screening route was used. Buccal swabs were obtained and analysed. Those who were identified as having at least one copy of the APOE‐ε4 genotype were invited to participate in the Generation program at Glasgow Memory Clinic. The Generation 2 Study pre‐dominantly focused on the recruitment of carriers of one copy of the APOE‐ε4 allele. An elevated Aβ result was also required, as measured by a PET scan and/or lumbar puncture procedure, to be eligible for randomisation.

Result

3672 buccal swabs were obtained during recruitment for the Generation program. Of these, 1056 were heterozygous for APOE‐ε4. 653 were screened and disclosed as heterozygous for APOE‐ε4 with 421 of these subjects enrolled in the Generation 2 Study. 223 subjects attended for amyloid testing. It was found that 72 subjects (32%) had elevated amyloid level as determined by PET scan or lumbar puncture. 61 subjects were randomised into the Generation 2 Study at the time of early termination of this clinical trial.

Conclusion

The Generation 2 Study enabled the effective identification of previously unidentified APOE‐ε4 carriers with elevated Aβ. This site’s screen fail rate was as anticipated with the majority of screen fails due to non‐elevated amyloid results.
A short assessment tool for small vessel disease with cognitive impairment: The Virtual Supermarket (VSM)
Authors: Boz Hatice Eraslan , Limoncu Hatice , Zygouris Stelios , Tsolaki Magda , Giakoumis Dimitris , Votis Konstantinos , Tzovaras Dimitris , Öztürk Vesile , Yener Görsev
Published: December 2020

Background

Detailed neuropsychological assessment is essential to detect cognitive impairment in SVD. Therefore, a brief cognitive test is needed as an alternative to extensive assessment (Peng et al., 2019). The aim of this study is to examine cognitive functions between SVD with cognitive impairment (SVD‐CI), cognitively normal SVD (SVD‐CN), and healthy controls (HC) using the Virtual Supermarket (VSM) application and whether the VSM correlates the traditional pencil‐and‐paper neuropsychological tests.

Method

Thirty‐two SVD‐CI, 37 SVD‐CN and 30 HC were included the study. All participants were applied to virtual reality‐based VSM with tablet and comprehensive neuropsychological tests. (Zygouris et al., 2015; Eraslan‐Boz et al., 2019).

Result

SVD‐CI patients were poorer performance in “Correct Types” (p<0.05), “Correct Money” (p < 0.05) and “Duration” (p < 0.001) compared to HC; and in “Bought Unlisted” (p < 0.05) and “Duration” (p < 0.001) compared to SVD‐CN. However, there was no significant difference between SVD‐CN and HC in VSM variables. In addition, all VSM variables had a discrimination ability with 81% correct classification rate (CCR), 78% sensitivity, and 83% specificity over SVD‐CI and HC. Moreover, “Duration” variables of the VSM was moderately related to composite z‐scores of general cognitive status (r = ‐0.491, p < 0.001), memory (r = ‐0.509, p < 0.001), language (r = ‐0.404, p = 0.001) and visuospatial functions (r =‐0.593, p < 0.001). “Correct Types” (rpb = ‐0.301, p = 0.012) and “Correct Money” (rpb = ‐0.335, p = 0.005) was associated with visuospatial function on SVD groups.

Conclusion

This study is the first to evaluate cognitive functions by means of the VSM in SVD in a Turkish speaking population. This study provides encouraging preliminary findings about possibility of the VSM as a tool in the assessment of cognitive impairment and differentiation SVD‐CI from HC.
“Dempathy” ‐ From empathy to synchronization in understanding people with dementia
Authors: Chui Kenny Chi Man
Published: December 2020

Background

In Hong Kong, dementia is one of the significant reasons for the family caregivers to send their beloved one to the residential care homes. Nevertheless, over 50% of current residents are in cognitive impairment and different stages of dementia. The caring staff face a lot of challenges and uncertainty, even worries and anxiety in taking care of people with dementia. How to facilitate the care staff to implement person‐centred care is what we all would like to find out. The research began two reflective training sessions, each of which lasted 90 minutes with over 25 frontline care staff, by presenting some of the subjective experiences of residents with dementia with the aim of arousing empathy for their self‐perceptions. Afterwards, I asked the attendees a series of reflective questions as prompts to promote their reconsideration of how people with dementia might be cared for by following the person‐centred approach. The same semi‐structured questions were designed for both focus groups to gain insight into the staff’s thoughts about the self‐perception of people with dementia and the reflective training. The participating care staff had reflected upon their attitudes, skills and knowledge related to dementia care. Hardly any care staff reported having ever thought about the self‐perception or subjective views of people with dementia. On the contrary, they had assumed that people with dementia were incapable of giving rational responses and that it was therefore unnecessary to listen to their points of view. Themes including (1) From Stigmatization to Acceptance; (2) From Perceiving the Patient to Perceiving the Person; (3) From Ignoring to Responding; (4) From Being Tasked‐Oriented to Being Relationship‐Oriented; (5) From Denying to Recognizing People with Dementia were found. In the focus groups, however, the care staff suggested that they had become aware of ways to understand people with dementia from their perspectives and in their context. The implementation of person‐centred approach is associated with the change of caring attitude and perception of dementia at the fundamental level. The reflective training facilitated the care staff to transform from empathy to synchronization towards the context of people with dementia, which I called “Dempathy”.
Dementia‐related psychosis in the United States: Estimated prevalence of patients treated with antipsychotics/mood stabilizers and methodology using third party claims database
Authors: Ramos Brett A. , Whitford Alex , Brain Cecilia
Published: December 2020

Background

Dementia affects approximately 8 million people in the US and about 2.4 million experience dementia‐related psychosis, such as hallucinations and delusions1‐15. However, the currently treated prevalence of psychosis in dementia is not well established. Currently there are no approved medications for dementia‐related psychosis and antipsychotics (APs)/mood stabilizers(MS) are commonly used to treat psychotic and behavioral symptoms.16‐19

Method

Initially Anonymous Patient Level Data was used to identify patients prescribed APs and/or MS in the 1 year index period. Presence of dementia before psychosis was confirmed through a 1‐year look‐back period based on Dx or Rx. APs/MSs were enforced to be subsequent to the dementia diagnosis and/or treatment within the study period. The cohort was then analyzed to determine whether conditions such as schizophrenia and bipolar disorder were significantly more commonly observed than in the general population to exclude selection bias. Lastly the raw patient data was projected to the total universe using known coverage ratios for the data set and specific cohort.

Result

After adjusting for non‐reporting sources, approximately 700,000 patients, who were identified by the methods criteria to have dementia and psychotic symptoms were prescribed APs based on the estimation. An additional 100,000 patients were prescribed MSs (but no APs) presumably due to dementia with psychosis.

Conclusion

Approximately 30% of persons with dementia suffer from psychosis and our findings suggest that only 33% of them are currently pharmacologically treated with APs and MSs, or ≤ 10% of about 8 million people with dementia. Further studies are needed to explore other potential therapies, usages, and treatments in this population.