bluuebunny/crossref_metadata_2025_split huggingface dataset:
Medical cannabis and cognitive performance in middle‐aged and old adults treated for chronic pain: A cross‐sectional analysis
Authors: Sznitman Sharon , Vulfsons Simon , Meiri David (Dedi) , Weinstein Galit 
Published: December 2020

AbstractBackgroundMedical cannabis (MC) policies are currently undergoing rapid changes, with increasingly more jurisdictions around the world legalizing MC for various indications, including chronic pain. These developments make it increasingly likely that the general population, and in particular older populations, will consume cannabis regularly. Indeed, MC treatment is particularly prevalent among older individuals. A major concern related to cannabis use, and particularly in aging populations, is potential effects on brain health. Yet, there is a dearth of studies examining cognitive effects of cannabis in older adults.MethodWe recruited 63 MC and 62 non‐MC chronic pain patients over the age of 50 years with chronic neuropathic pain of organic origin from the Rambam Pain Medicine clinic in Haifa, Israel. Cognitive performance was assessed after abstinence of 8h in the MC users through CogState, a computerized battery designed to assess psychomotor reaction time, attention, working memory and learning. Linear regression models were used to test differences in cognitive performance between the two groups. Models adjusted for age, sex, education, cardiovascular disease and depression. Among MC users, the associations of dosage, cannabinoid concentrations, length and frequency of use and hours since last use with cognition were also examined.ResultMean age was 63±6 and 60±5 years in the non‐MC and MC patients respectively. MC patients were more likely to have cardiovascular disease (3% vs. 11%, respectively, p=0.025) and depression (7% vs. 21%, respectively, p=0.003). Sex, education levels, alcohol and cigarette use patterns and pain levels were similar. After adjustment, there were no significant difference between MC and non‐MC patients in any of the cognitive performance measures. Furthermore, years of MC use, frequency of use, hours since last use, number of strains used, THC/CBD concentration or dose were not related to cognitive performance on the different tests.ConclusionThese results suggest that use of whole plant MC cannabis does not have a widespread impact on cognition in older patients. Considering the accumulating evidence showing efficacy of cannabis use for multiple health conditions, the lack of adverse effects on the brain can eliminate concerns and contribute to a better risk‐benefit assessment of MC treatment.
Prevalence and severity of neuropsychiatric symptoms in the prodromal stages of dementia with Lewy bodies and Alzheimer’s disease
Authors: Wyman‐Chick Kathryn A. , Erickson Lauren O. , Rosenbloom Michael H. , Weintraub Daniel , Barclay Terry R. , Barrett Matthew J. 
Published: December 2020

AbstractBackgroundThere has been minimal investigation into the prodromal features dementia with Lewy bodies (DLB) and how they may differ from prodromal features of Alzheimer’s disease (AD).MethodThe data analyzed for this investigation were collected as part of a large, prospective longitudinal study conducted by the National Alzheimer’s Coordinating Center (NACC database is funded by NIA/NIH Grant U01 AG016976). We identified 110 non‐demented participants who converted to DLB at a subsequent visit. Participants were age and sex matched to 220 non‐demented participants who later converted to AD. We examined between group differences in the prevalence of symptoms on the Neuropsychiatric Inventory Questionnaire (NPI‐Q) at time of dementia diagnosis and in the 1‐3 years preceding conversion to dementia using Chi‐Square or Fisher Exact Test analyses.ResultsFor the DLB and AD groups, 82% were male and the average age at the time of dementia diagnosis was 75.4 years (SD=7.9). There was no significant difference in education between the two groups. The DLB group was significantly less culturally diverse than the AD group (See Table 1). Nighttime behaviors and hallucinations were significantly more common in the DLB group compared to the AD group at all time points during the prodromal phase and at the time of dementia diagnosis. There was no significant difference in the informant’s report of motor symptoms in the prodromal phases between the two groups (See Table 2).ConclusionThe DLB group demonstrated a significantly higher prevalence of nighttime behaviors and hallucinations than the AD group in both the prodromal phase and at the time of dementia diagnosis. These findings support the occurrence of core clinical features of DLB during the prodromal phase of the disease [1]; however, there was no significant difference in the informant’s report of motor symptoms within the prodromal phases, which warrants a comparison utilizing more objective motor data. Reference: 1. McKeith IG, Boeve BF, Dickson DW, et al.; Dementia with Lewy Bodies Consortium. Diagnosis and management of Dementia with Lewy Bodies: Fourth consensus report of the DLB Consortium. Neurol. 2017;89:1‐13.
Economic status and mortality in Alzheimer's disease patients in Japan: LIFE Study
Authors: Ono Rei , Maeda Megumi , Fukuda Haruhisa 
Published: December 2020

AbstractBackgroundAlzheimer's disease (AD) is an urgent global health priority, with a projected 75 million cases by 2030 and 131 million cases by 2050 worldwide. Low economic status in patients may affect prognoses by limiting the opportunities to receive appropriate care. However, the association between economic status and mortality among AD patients in Japan is unclear. This study sought to examine the influence of economic status on mortality in individuals with AD in Japan.MethodClaims data from April 2014 to March 2019 were obtained from the Longevity Improvement & Fair Evidence Study (LIFE Study) database, which contains municipality‐level information. The study subjects were individuals residing in one rural city who received new diagnoses of AD in October 2014 or later. To analyze economic status, we examined the utilization of a program designed to reduce the maximum healthcare expenditures for low‐income individuals. Subjects who were enrolled in this program upon receiving a new AD diagnosis were designated low‐income individuals. All subjects were tracked for a maximum of 54 months following AD diagnosis, and the number of months before a mortality event was assessed. The hazard ratio (HR) for mortality in low‐income individuals was estimated using a Cox proportional hazards model that adjusted for sex, age, Charlson comorbidity index, healthcare expenditures in the 6 months before AD diagnosis, and anti‐dementia drug use.ResultWe identified 1,571 newly diagnosed AD patients from the LIFE Study database. The mean age was 83.6 years, 68.1% were women, and 17.5% were low‐income individuals. With a mean follow‐up period of 24.8 months, the mortality rate was 21.3% (334 subjects). The survival rates were 88.7% and 75.0% after 12 and 36 months of follow‐up, respectively. The HR (95% confidence interval) for mortality was 2.18 (1.69‐2.80) for low‐income individuals and 2.15 (1.71‐2.72) for men.ConclusionLow‐income status was associated with substantially poorer prognoses in new AD cases. These findings indicate a need for a thorough examination of the medical and nursing care services utilized by low‐income individuals with AD, and for an exploration of improvement strategies.
Characterization of subjective cognitive concerns (SCC) in a racially/ethnically diverse community‐based elderly cohort: Results from the Einstein Aging Study (EAS)
Authors: Katz Mindy J. , Wang Cuiling , Mogle Jacqueline , Rabin Laura 
Published: December 2020

AbstractBackgroundSCC may play an important role in identification of pre‐clinical dementia, especially among individuals who experienced disparities. A small number of studies examined the differential prediction of objective cognitive decline between blacks and whites using SCC, yielding mixed results. It is important to identify any differential patterns of SCC endorsement among racially diverse groups to enhance the ability to capture current and future cognitive status.MethodUsing data from the EAS, a longitudinal community residing cohort aged 70+, an SCC composite was derived using 22 self‐reported items. Cognitive status was diagnosed by consensus conference (dementia, MCI, cognitively normal). Objective cognition was measured using 3 factor scores (memory, executive function, global/verbal) derived from a principal component analysis of our neuropsychological battery. Multiple linear regression models were used to evaluate racial differences in SCC at baseline for those who were cognitively normal, as well as to determine whether there was a differential association between SCC and objective cognition among racial groups. Cox models were applied to determine if there was racial heterogeneity for the effect of SCC on incident MCI, adjusting for demographics, estimated premorbid intelligence, medical co‐morbidities, and depressive symptoms.Result1720 participants of non‐Hispanic white or black race were cognitively normal at baseline and included in these analyses. There was no significant difference between blacks and whites on the SCC composite; however, there was a significant interaction between race and SCC on 2 of 3 objective cognition factors. Having more SCC at baseline was associated with worse objective cognitive performance in the memory and global/verbal domains in white and black participants, but the association was significantly weaker among blacks. While SCC was associated with greater risk of incident MCI (<0.0001), there was no significant interaction between race and SCC on incident MCI.ConclusionDespite having weaker, though still significant, associations with memory and global/verbal tasks in blacks compared to whites, SCC consistently predicted incident MCI across the two races. Future work should expand upon these results through replication in other diverse samples, inclusion of informant report data, and investigation of differential change in SCC over time and in relation to clinical conversion.
Soluble TNF mediates high‐fat and high‐carbohydrate diet–induced inflammation, alterations in peripheral blood and brain immunophenotype, and gut microbiome in a mouse model of amyloid pathology
Authors: Herrick Mary K. , MacPherson Kathryn P. , Eidson Lori N. , de Sousa Rodrigues Maria Elizabeth , Sniffen Lindsey J. , Wallings Rebecca , Kelly Sean D. , Hamilton Adam M. , Oliver Danielle , Yang Yuan , Chang Jianjun , Keating Cody E. , Coomes Alexandra , Sampson Timothy R. , Jobin Christian , Norris Christopher M. , Barnum Christopher , Tansey Malu Gamez 
Published: December 2020

AbstractBackgroundSporadic Alzheimer’s disease (AD) is a product of complex gene‐environment (GxE) interactions. Central‐peripheral immune cell crosstalk and traffic across the blood‐brain barrier (BBB) have been implicated in AD pathophysiology by recent studies that demonstrate a T‐cell signature in AD brain, gut dysbiosis in AD patients, and a significant epidemiological association between metabolic syndrome, obesity, and type‐2 diabetes with increased incidence of AD. Soluble tumor necrosis factor (sTNF), a known regulator of BBB and gut‐epithelial barrier permeability in chronic systemic inflammatory diseases that is increased in AD patient blood, was investigated as a regulator of immune cell traffic and AD‐like pathology in a mouse model of amyloid pathology subjected to an obesogenic diet.MethodTo investigate the effects of chronic peripheral inflammation on neuroinflammation and AD‐associated pathology, 2‐month old female 5xFAD (Tg) or non‐Tg mice were fed a high‐fat high‐carbohydrate diet (HFHC) or a balanced control diet (CD) for 8 weeks. After 4 weeks of diet, BBB‐permeant XPro®1595 was given subcutaneously every third day to selectively inhibit sTNF signaling. Neuroimmunological, histological, biochemical, genomic, and transcriptomic analyses were used to analyze effects on blood and brain immune populations, BBB permeability, inflammatory gene and protein expression, and gut microbiome.ResultHFHC‐fed Tg mice showed decreased T cell numbers in the blood and increased Ly6C+ T cells in the brain as compared to Tg mice fed CD or non‐Tg HFHC‐fed mice. Tg mice fed HFHC diet displayed increased hippocampal TNF and ZO‐1 mRNA, modestly increased Aβ burden, and marked increases of Iba1+ cells. Analysis of gut microbiota revealed significant beta diversity genotype‐ and diet‐dependent differences between Tg and non‐Tg mice, synergy in GxE interactions, and the ability of XPro®1595 to reverse many of these features.ConclusionTogether, these data suggest that an obesogenic diet enhances BBB permeability, disrupts innate and adaptive immune cell populations in the blood, promotes gut dysbiosis, and enhanced traffic of immune cells to the CNS through sTNF‐dependent mechanisms. Clinical trials in patients with MCI/early AD are underway to investigate the ability of a weekly dose of XPro1595 to reduce underlying inflammation without immunosuppression via selective targeting of sTNF.
Application of machine learning to predict amyloid, metabolic, and structural neuroimaging biomarkers in the progression of autosomal dominant Alzheimer disease
Authors: Luckett Patrick H. , McCullough Austin A. , McDade Eric , Benzinger Tammie L.S. , Morris John C. , Bateman Randall J. , Ances Beau M. 
Published: December 2020

AbstractBackgroundModels of disease progression in autosomal dominant Alzheimer disease (ADAD) using multimodal neuroimaging, deep learning, and feature extraction algorithms were designed.MethodLongitudinal structural magnetic resonance imaging (MRI), amyloid positron emission tomography (PET) and fluorodeoxyglucose (FDG) PET were acquired in 131 mutation carriers (MC) and 74 non‐carriers (NC) from the Dominantly Inherited Alzheimer Network observational study; the groups were matched for age, education and sex. Imaging data were evaluated with regard to expected years to symptom onset (EYO), apolipoprotein e4 (APOE e4) status, age, and gender. A deep feedforward neural network was trained to predict disease progression with respect to the given neuroimaging modality. Relief feature selection algorithms identified brain ROIs that were the strongest predictors of mutation status. Model simulations identified amyloid, metabolism, and atrophy trajectories, and ROC analysis identified cutoff values.ResultThe Relief algorithm identified the caudate, anterior cingulate, and precuneus as the strongest predictors amongst all modalities (Figure 1). The model yielded accurate results for predicting future PiB (R2 = 0.95, root mean squared error [RMSE] = 0.2), FDG (R2 = 0.93, RMSE = 0.1), and brain atrophy (R2 = 0.95) in MCs compared to NCs (Figure 2). Simulations revealed a sigmoidal trajectory for PiB, a biphasic response for FDG, and a gradual decrease in brain volume (Figure 3). Cutoff values were identified for PiB (caudate = 1.3, total cortical mean = 1.2), FDG (caudate = 1.4, total cortical mean = 1.6), and Volumes (caudate = 3.3k, total cortical mean = 575k) (Figure 4).ConclusionTo provide targeted care for individuals with ADAD, novel methods are needed to model disease trajectories. Our model is accurate and capable of reliably forecasting future changes in amyloid deposition, glucose metabolism, and brain volume. The data‐driven approach represents an opportunity to discover novel mechanisms and disease trajectories in ADAD.
Impact of APOE4 and future family history on early adulthood cardiovascular risk: Results from a 30‐year cohort study
Authors: Koychev Ivan , Vaci Nemanja , Moonen Justine E , Yaffe Kristine , Nasrallah Ilya M , Sidney Stephen , Jindra Christoph , Gallacher John , Launer Lenore J 
Published: December 2020

AbstractBackgroundSelected cardiovascular factors, APOE ε4 allele carriership and family history of dementia (FHD) are robust risk factors for late‐onset dementia. While it is recognised that cardiovascular factors exert their influence from mid‐age, it is unclear whether APOE ε4 carriership and a future FHD impact the process. Here we test the hypothesis that genetic and familial susceptibility for dementia are associated with an unfavourable cardiovascular risk profile starting from early adulthood.MethodWe used data from the CARDIA study which followed‐up 5116 individuals aged 18‐30 starting in 1984. Data from 2,497 30‐year visit attendees (mean age 55) was used to assess the associations of APOE ε4 carriership and future FHD with baseline and 30‐year measures of cardiovascular risk factors (LDL, HDL, glucose, blood pressure, BMI) suggested to be associated with late‐life cognitive impairment.ResultAPOE ε4 carriers, compared to non‐carriers, had higher LDL and lower HDL levels in early adulthood. Future FHoD was associated with worse late‐life but not baseline lipid profile. Compared to those with neither or one, persons having both FHD and APOE ε4 had the lowest baseline mean HDL and highest mean LDL (52 and 117 mg/dL for APOE ε4+/FHD+ versus 54 and 107 mg/dL for APOE‐/FHD‐ respectively). Interestingly, APOE ε4+/FHoD+ was associated with lower systolic and diastolic blood pressure relative to the APOE ε4‐/FHD‐ group in early adulthood but not year 30. Neither family history nor APOE ε4 were associated with early or late‐life levels of blood glucose or, BMI.ConclusionOur results indicate that APOE ε4 allele carriership associates with an unfavourable lipid profile (low HDL, high LDL) starting from early adulthood continuing into later life. Of the two factors, APOE ε4 allele carriership was more strongly associated with lipid levels, but family history of dementia does add some additional explanatory value to the association. Recent GWAS have identified cholesterol metabolism as a component of risk for dementia, and these results indicate that APOE ε4 allele effects peripherally measured lipids, starting at the latest in early adulthood. The relation between these levels and brain structure and function needs further evaluation.
Neuropathological diagnoses of subjects autopsied in the phase 3 clinicopathological study of flortaucipir F18 PET imaging
Authors: Beach Thomas G. , Montine Thomas J. , Serrano Geidy E. , Sue Lucia I. , Intorcia Anthony J. , Fleisher Adam S. , Pontecorvo Michael J. , Devous Michael D. , Lu Ming , Mintun Mark A. ,   A16 Study Investigators
Published: December 2020

AbstractBackgroundAvid Radiopharmaceuticals conducted a prospective case‐control clinicopathological study of flortaucipir F18 PET Imaging (AV‐1451‐A16) from October 2015 through June 2018. This presentation is an initial report of the detailed neuropathological findings of the 67 primary study subjects.MethodSixty‐seven valid study autopsies were performed. The cerebral patterns of flortaucipir PET images were visually assessed and compared to the patterns of immunohistochemical tau pathology. The study met pre‐specified success criteria, with imaging predicting an NIA‐AA B3 level of tau pathology (Braak V/VI) and a high level of Alzheimer’s disease neuropathologic change.ResultThere were 35 females and 32 males, mean age 82.6 (SD 9.4). Fifty‐three cases met intermediate or high ADNC levels, consistent with AD as a cause of cognitive impairment. Of these, many had additional major neuropathological findings (not mutually exclusive), meeting neuropathological diagnostic criteria for dementia with Lewy bodies (DLB; n=7), Parkinson’s disease (PD; n=1), progressive supranuclear palsy (PSP; n=5), hippocampal sclerosis (HS; n=5), vascular dementia (n=3) and corticobasal degeneration (CBD; n=1), while others had lesser findings of TDP‐43 proteinopathy restricted to the mesial temporal lobe (n=19), Lewy body pathology not meeting criteria for DLB or PD (n=18), age‐related tau astrogliopathy (ARTAG; n=15) or remote cerebral infarcts (n=10). Cases with less than intermediate ADNC (n=14) met neuropathological diagnostic criteria (not mutually exclusive) for PD (n=2), HS (n=2), DLB (n=1), PSP (n=1), CBD (n=1) and others had additional neuropathological findings of TDP‐43 proteinopathy restricted to the mesial temporal lobe (n=2), Lewy body pathology not meeting criteria for DLB or PD (n=4), ARTAG (n=3) or remote cerebral infarcts (n=2).ConclusionThis high proportion of mixed neuropathology is typical of what has been published for other elderly autopsied subjects. Correlations of flortaucipir F18 PET imaging with these varied neuropathological types will be undertaken.
Standing activity as assessed by seismic accelerometers and cognitive function in community‐dwelling older adults: The MIND trial
Authors: Halloway Shannon , Dhana Klodian , Desai Pankaja , Barnes Lisa L , Aggarwal Neelum T , Evers Jordi , Sacks Frank , Carey Vincent , Morris Martha Clare 
Published: December 2020

AbstractBackgroundFew older adults are able to achieve recommended levels of moderate‐vigorous physical activity despite known cognitive benefits. Alternatively, small movements, such as increasing movement while standing during usual tasks, can easily be integrated into daily routines by older adults. However, standing activity is best assessed with specific devices (i.e., seismic accelerometers). No existing study of older adults has examined the impact of device‐measured standing activity on cognition. Therefore, the purpose of this secondary analysis is to examine the association between standing activity (as measured by a seismic accelerometer) and cognition in cognitively healthy older adults.MethodParticipants were 98 cognitively healthy adult participants aged 65 years or older with family history of dementia from the ongoing MIND trial (NCT02817074), which tests the effects of a 3‐year diet intervention on cognitive decline. Exclusion criteria included diagnosis or symptoms of mild cognitive impairment or dementia. Linear regression analyses tested cross‐sectional associations between standing intensity and cognition. Standing activities were mean intensity of standing and static activities (sum of standing and shuffling) assessed by the MoveMonitor+ accelerometer/gyroscope. Cognition was composed of 4 cognitive domains constructed from 12 cognitive performance tests.ResultParticipants were on average 69.7 years old (SD=3.7), 69.4% women, and 73.5% had a college degree or higher. Both higher mean intensity of standing activity and static activity were significantly associated with higher levels of executive functioning and perceptual speed in models adjusted for age, gender, and education. Each log unit increase in standing activity intensity was associated with 0.77 units higher of executive function (p=.041), and 0.85 units higher of perceptual speed (p=.032). For static activities, significant log unit increases were 0.86 (p=.009) for executive function and 0.96 (p=.006) for perceptual speed. When we additionally adjusted for time spent in moderate‐vigorous physical activity and cognitive activity, the positive associations between higher intensity of standing and static activity and perceptual speed remained.ConclusionThese findings suggest the importance of considering intensity of standing activity in cognition. The relationships should be further explored in longitudinal analyses and interventions that incorporate small changes to daily routines in addition to promoting moderate‐vigorous physical activity.