bluuebunny/crossref_metadata_2025_split huggingface dataset:
INCREASE‐DEPTH: MTM and DEPrescribing THerapy recommendations for medication‐related problems among elderly adults in the INCREASE trial
Authors: Smith Noah I , Huffmyer Mark , Eckmann Lynne , Martinez Ashley I , Beech Brooke F , George Rosmy , Abner Erin L , Jicha Gregory A , Moga Daniela C 
Published: December 2021

AbstractBackgroundA growing body of literature supports the hypothesis that cognitive reserve (CR) may offset the characteristic progression of dementia symptomatology. The cognitive function of polypharmacy‐prone populations, such as older adults, can be negatively impacted by various factors, including medication‐related exposures. The INCREASE trial prospectively measures the effect of targeted medication management therapy (MTM) services for medication‐related problem (MRP) reduction, maintaining CR, and delaying AD manifestations.MethodCommunity‐dwelling individuals aged ≥65 years, routinely exposed to ≥1 potentially inappropriate medication (PIM), and without baseline dementia were recruited for the INCREASE trial. Pharmacists board certified in geriatrics provided blinded comprehensive medication review (CMR) to identify MRPs (e.g., per 2015 Beers Criteria, drug‐drug/drug‐disease interaction, etc.) for all patient‐reported prescriptions, over‐the‐counter (OTC) drugs, vitamins, and supplements. Individualized risk‐benefit assessments and plans were discussed collaboratively between pharmacists, clinicians, and participants. Recommendations were categorized by medication type and recommendation type (e.g., adjusting medication exposure, non‐pharmacologic intervention, etc.) and identifying potential drug‐drug or drug‐disease interactions.ResultOf 104 participants recruited for the study, 90 were randomized; mean (SD) age at enrollment was 75.3 (8.5), with 64% female, and 89% Caucasian. Baseline CMRs identified 6.8 (SD 3.6) MRPs per participant, 2.4 (SD 1.3) of which were PIMs per 2015 Beers Criteria (Table 1). Almost half of MRPs involved medications available without a prescription (e.g., acid suppressants, diphenhydramine, vitamins, etc.). CMRs also identified 0.94 (SD 1.35) drug‐drug and 0.98 (SD 1.07) drug‐disease interactions of concern per patient. Recommendations to optimize treatment included switching therapy (27%) or stopping/reducing medication exposure (22%) (Table 2).ConclusionCMR and MTM prompts nuanced discussion between healthcare providers and patients, highlighting many drug‐related safety concerns. Certain implicated medications may be potentially associated with CR and/or dementia (e.g., anticholinergics). This analysis describes the baseline MTM recommendations provided by blinded pharmacy specialists in the INCREASE trial before randomization and participant intervention. Final recommendations for those randomized to the intervention were made after the pharmacists‐clinician team met with the participant. Evaluation of CR preservation and delay of AD onset post‐randomization are pending completion of the data collection (anticipated data collection completion by March 31, 2021).
Sex differences in levels of plasma neurofilament light and total tau in adults with Down syndrome
Authors: Dang Lam‐Ha T , Krinsky‐McHale Sharon J , O'Bryant Sid , Pang Deborah , Zigman Warren B. , Silverman Wayne , Schupf Nicole , Lee Joseph H. 
Published: December 2021

AbstractBackgroundPlasma neurofilament light (NfL) and total tau (t‐tau) are emerging as promising biomarkers of Alzheimer’s disease (AD) in adults with Down Syndrome (DS). Sex may influence the levels of these biomarkers however, research on sex differences in these biomarkers is limited. In this study, we examined whether sex influences plasma levels and clinical classification accuracy of NfL and t‐tau.MethodWe performed a cross‐sectional analysis of 275 adults with DS (106 males; 169 females) from a community‐based cohort. Levels of plasma NfL and t‐tau were measured using the Simoa platform. Based on consensus diagnosis using a battery of direct neuropsychological testing and informant interviews, participants were classified into three clinical dementia groups: cognitively stable (CS), mild‐cognitive impairment (MCI‐DS) and Alzheimer’s dementia (AD‐DS). Two‐way analysis of covariance was used to assess group differences in males and females, adjusting for age. Post‐hoc pairwise comparisons were adjusted for multiple comparisons using the Bonferroni correction. Receiver operating characteristic analyses were conducted to evaluate the performance of the biomarkers to classify dementia status in males and females, separately.ResultIn this study, 27 (16%) and 10 (6%) females while 12 (11%) and 13 (12%) males exhibited MCI‐DS and AD‐DS, respectively. Females were, on average, 4.5 years younger than males. Age‐adjusted levels of plasma t‐tau (pinteraction = 0.047), but not NfL (pinteraction = 0.138), significantly differed by sex. NfL levels were higher in MCI‐DS and AD‐DS groups than in the CS group in both sexes (all padjusted < 0.05). T‐tau levels were significantly higher in the MCI‐DS and AD‐DS (both padjusted < 0.01) groups than in the CS group in females but did not differ across clinical groups in males. NfL showed excellent accuracy in females (range AUCNfL: 0.74‐0.97) and males (AUCNfL: 0.71‐0.88), while t‐tau showed classification utility in females (AUCt‐tau:0.69‐0.90), but not in males (AUCt‐tau: 0.48‐0.66).ConclusionOur findings suggest that levels and accuracy of plasma NfL and t‐tau to classify dementia differed by sex in adults with DS. These differences underscore the need to further elucidate sex specific patterns of fluid biomarkers, critical in the development of personalized medicine approaches in AD.
Visual memory test equal to commonly used verbal memory test in predicting tau in the medial temporal lobe
Authors: Poltronetti Nina Margherita , Arias Jaime Fernandez , Pallen Vanessa , Lussier Firoza Z , Therriault Joseph , Mathotaarachchi Sulantha , Tissot Cécile , Benedet Andréa Lessa , Wang Yi‐Ting , Pascoal Tharick A. , Stevenson Jenna , Rahmouni Nesrine , Bezgin Gleb , Gauthier Serge , Rosa‐Neto Pedro 
Published: December 2021

AbstractBackgroundThe Aggie Figures Learning Test (AFLT) is a visual memory assessment tool, constructed as an analog to the Rey Auditory Verbal Learning Test (RAVLT). The AFLT includes three sequences of abstract drawings as stimuli –a primary set which is repeated across five trials, an interference set, and a recognition set. After about twenty minutes, the test assesses free delayed recall (DR) and delayed recognition of the learned material. This test is very similar to the RAVLT in terms of administration; therefore, the present study will evaluate whether the predictive value of DR scores from both tests is comparable in relation to Tau PET.MethodTau PET ([18F]‐MK6240) was acquired for 130 individuals for analysis involving only AFLT, 139 for analysis involving only RAVLT, and 127 individuals for analysis including both AFLT and RAVLT. Demographic data is shown on Tables 1, 2, and 3. MRI were segmented into probabilistic grey (GM) and white (WM) maps, non‐linearly registered to the ADNI template using Dartel and smoothed with an 8mm FWHM gaussian kernel. Voxel‐wise linear regression models were applied, using VoxelStats, with Tau PET as the dependent variable and either DR AFLT or DR RAVLT as predictors. We ran three analyses where one included both DR scores. Additionally, we corrected for age, sex, diagnosis, APOE, and amyloid load. All other variables that were tested did not significantly contribute to predict Tau PET.ResultWe found negative associations between tau binding in the medial temporal lobe and both DR scores when looking at each of them separately. More importantly, we found that DR AFLT scores lose their predictive value when including DR RAVLT in the same model.ConclusionOur results support the use of both tests interchangeably when testing memory in elderly populations, even though they tap into two different modalities. This piece of evidence confirms what was reported by the authors who published the original AFLT article. Nonetheless, that article dealt with a sample whose demographics and clinical presentation strongly differed from those of our sample.
Effects of GERAS DANCE on cognitive function in older adults with and without cognitive impairment
Authors: Hewston Patricia , Kennedy Courtney , Ioannidis George , Merom Dafna , Marr Sharon , Hladysh Genevieve , Papaioannou Alexandra 
Published: December 2021

AbstractBackgroundMild cognitive impairment (MCI) is highly prevalent in older adults aged 60+ with prevalence rates of 16‐20% and one of the first cognitive expressions of Alzheimer's Disease and other dementias. Dance activates many brain regions to integrate complex movement patterns with musical and emotional expression and may lower the risk of dementia over time. We investigated the effect of 12‐weeks of GERAS DANcing for Cognition and Exercise (DANCE) on cognitive function in older adults (aged 60+) with and without cognitive impairment.MethodsGERAS DANCE is a specialised program tailored for older adults with early memory or mobility problems. It was offered across 12 YMCAs in Southern Ontario, Canada with in‐person classes 2x weekly (1‐hour each) and homework (10‐minutes daily) for a period of 12 weeks. Cognitive function was assessed with the Montreal Cognitive Assessment [MOCA]. Changes in cognitive function from baseline to 12 weeks were evaluated using ANOVA [2 (Time: pre‐ post‐intervention) x 2 (Group: cognitive impairment, no cognitive impairment)].ResultA total of 106 older adults participated in the analysis (mean age = 76.12 ± 7.03, range 61 to 93 years, 81% female). Overall GERAS DANCE improved cognitive function [F(1,105) = 4.928, p = 0.029]. In older adults with cognitive impairment, the mean difference of MOCA total scores improved by 1.04 points (pre = 21.71 ± 3.34, post = 22.74 ± 4,12).ConclusionGERAS DANCE has the potential to improve or maintain cognitive function in older adults with and without dementia. Next steps include testing for efficacy of GERAS DANCE as a part of an overall approach for cognitive health and to inform clinical practice guidelines.
Emotion regulation in mild cognitive impairment and subjective cognitive decline
Authors: Mah Linda , Vandermorris Susan , Verhoeff Nicolaas Paul L.G. , Herrmann Nathan 
Published: December 2021

AbstractBackgroundOur previous research in emotional verbal memory in mild cognitive impairment (MCI) and work from others suggest the hypothesis that emotion dysregulation is a signature of Alzheimer’s disease (AD) risk. Whether subjective cognitive decline (SCD), conceptualized as a possible preclinical stage of AD, is associated with emotion dysregulation is unknown. In the current study, we compared responses on the Cognitive Emotion Regulation Questionnaire (CERQ) and behavioural responses on a threat task amongst SCD, MCI, and cognitively unimpaired (CU) older adults.MethodsThe sample included 146 older adults free of lifetime history of psychiatric illness/neurological conditions: 33 MCI [17F, age 72.3(SD7.6)] defined as subjective memory/other cognitive complaints, impaired neuropsychological (NP) test performance, and functional independence, 71 SCD [49F, age 71.1(SD6.3)] based on subjective memory decline with worry with normal NP performance, and 42 CU [27F, age 70.6(SD6.8)] based on absence of subjective memory decline and normal NP test scores. Participants completed the CERQ which assesses cognitive coping strategies in negative emotional situations. A subset (19 MCI, 43 SCD, 19 CU) completed a computerized task in which they rated a physical feature or threat level of faces with varying degrees of threat. Multivariate ANOVA was used to examine group differences, followed by Sidak‐adjusted post hoc comparisons.ResultsOn the CERQ, groups differed in use of catastrophizing [F(2, 142)=3.51, P=.032], with a trend for use of rumination (P=.07), attributable to greater use of both strategies in MCI compared to CU (P=.04). On the threat task, groups differed in response latencies to judging physical features of threatening faces relative to neutral [F(2, 78)=3.17, P=.048)]. Relative to CU, SCD participants were slower to make physical judgements of threatening faces compared to neutral (P=.026).ConclusionsOlder adults with SCD do not report greater use of maladaptive emotion regulation strategies compared to CU. However, alterations in behavioural responses to threat versus neutral in SCD may represent deficits in regulating attention towards negative emotional information, similar to mood‐congruent cognitive biases observed in depression. These preliminary data highlight the need to increase our understanding of explicit and implicit emotional processing in older adults at risk for AD.
Telehealth‐based assessment of cognition in older adults during COVID‐19 and beyond
Authors: Cullum Munro 
Published: December 2021

AbstractBackgroundEvidence supporting the use of telehealth techniques in the assessment and diagnosis of dementia has been growing steadily. This began with the use of telephone‐based cognitive screening in the 1980s and televideoconference‐based assessments in the 2000s. The COVID19 pandemic brought telehealth suddenly to the forefront of healthcare, particularly for aging and at‐risk populations, as well as for clinical providers and researchers. While clinicians have been challenged to continue to provide patient care in a safe manner, researchers have been faced with the challenge of maintaining study protocols and continuing to advance the science of dementia. Fortunately, a growing body of research has demonstrated the feasibility, reliability, validity, and consumer acceptability of telehealth‐based assessment procedures, including teleneuropsychological (teleNP) techniques.MethodWe first reported results from a study of 202 adults age 50‐85 using a brief battery of common neuropsychological tests administered via teleNP vs in‐person in counterbalanced fashion which showed generally strong intraclass correlations (Cullum et al., 2014). Additional studies have since examined the validity and consumer acceptability of teleNP assessment in older adults, including recent reviews and findings from surveys and observations using teleNP during the COVID19 pandemic.ResultOur initial investigation revealed essentially equivalent results across teleNP vs traditional in‐person test conditions, with intraclass correlations around .80 and high levels of satisfaction with the procedures. Additional findings revealed validity by the discrimination of impaired and non‐impaired older adults with and without cognitive impairment similar to traditional in‐person assessment. Subsequent studies and reviews have added to this growing body of literature supporting the use of teleNP in older adults.ConclusionIn this presentation, the literature supporting the evidence for telehealth applications in the assessment and diagnosis of dementia will be reviewed, along with commonly used assessment instruments. A critical review of the strengths and limitations of remote clinical/cognitive evaluations as applied to aging individuals with and without cognitive impairment will be provided, along with practical recommendations for application of these procedures, including in‐home and computerized evaluations. Last, needs, opportunities, and future directions for remote cognitive assessment in clinical and research settings, including large‐scale surveillance and treatment studies, will be discussed.
Utility and usability of brief, remote, and self‐administered cognitive assessment for older adults with intact cognition and mild cognitive impairment: A novel approach to increase access during the COVID‐19 pandemic
Authors: Dorociak Katherine E , Mattek Nora , Lee Jonathan , Leese Mira I , Bouranis Nicole , Imtiaz Danish , Gothard Sarah , Kaye Jeffrey A , Hughes Adriana M 
Published: December 2021

AbstractBackgroundGiven the COVID‐19 pandemic and necessary restrictions on older adults’ in‐person clinical and research exposure, there is an urgent need for validated cognitive measures that can be self‐administered remotely in the home to expand the reach of cognitive assessment. The current presentation describes the implementation, validity, and usability of the Survey for Memory, Attention, and Reaction Time (SMART) assessment protocol that has been deployed in longitudinal cohort studies of older adults for over two years.MethodParticipants were 69 older adults classified as cognitively intact (n=44) or mild cognitive impairment (MCI; n=25). The SMART was sent to participants via email once per month. Participants completed SMART using their computer (n=55), tablet (n=10), or smart phone (n=4). The SMART consists of four face‐valid cognitive tasks available in the public domain assessing visual memory, attention, processing speed, and executive functioning. Participants also completed a neuropsychological battery and self‐ and informant‐rated measures of everyday cognition. Primary SMART outcomes consisted of subtest completion time; secondary meta‐metrics included outcomes indirectly calculated within the SMART (e.g., click count, total completion time). Analyses were based on initial SMART administration.ResultStepwise logistic regression analyses indicated that the SMART executive functioning subtasks (Trails B Completion Time (p=.05) and Stroop Click Count (p=.02)) were the strongest predictors of cognitive status (MCI vs. cognitively intact). Longer Total Completion Time (i.e., worse performance) on the SMART was correlated with reduced global cognition and lower self‐ and informant‐rated perceptions of everyday cognition (p<.05). The SMART was rated as highly usable (M=21.8 out of 25), with no difference in MCI and cognitively intact group scores. Over a three‐month period, 87% of participants completed the SMART within the first three days of receiving it, with 100% completion following a reminder call.ConclusionThis study provides preliminary support for remote, self‐administered cognitive assessment of cognitively intact and MCI older adults using the SMART. Given the prevalence of executive functioning deficits among non‐amnestic MCI presentations, the SMART may prove particularly valuable for increasing access to cognitive assessment for diverse, heterogenous older adults with increased vascular risk factors, medical comorbidities, and health disparities.
Activity‐dependent dysfunctional gene expression patterns are normalized by in vivo treatment of late‐stage Aβ pathology mice with a TrkB/C small molecule ligand
Authors: Latif‐Hernandez Amira , Moran‐Losada Patricia , Yang Tao , Tran Kevin C , Liu Harry , Butler Robert R. , Massa Stephen M. , Longo Frank M. 
Published: December 2021

AbstractBackgroundNeurotrophin signaling via TrkB and TrkC receptors participates in long‐term potentiation (LTP), a biological substrate of memory formation that is disrupted by amyloid‐β (Aβ) in APP mice. In this study, we ask whether there are alterations in activity‐dependent gene expression signatures in APP mice, and if so, could elements of these alterations be restored by prior treatment with a small molecule TrkB/C partial agonist, PTX‐BD10‐2.MethodWe administered PTX‐BD10‐2 (50 mg/kg) or vehicle (VEH) orally once daily to male wild type (WT) and APP mice expressing London and Swedish mutations (APP‐L/S) for 3 months starting at 13 months of age. Paired‐pulse ratios (PPR) and Theta Burst Stimulation (TBS) were applied to acute hippocampal slices, in absence of drug, to induce short and long‐term synaptic plasticity. Upon completion of recordings, we examined whole tissue transcriptomic profiles for differential gene expression and enrichment of ontological terms and pathways.ResultPronounced deficits in PPR (at 10 and 20 ms) and LTP were found in APP‐L/S relative to WT slices, and entirely restored in slices from APP‐L/S mice treated with PTX‐BD10‐2 (Fig. 1). To identify candidate mechanisms of this pre/post synaptic plasticity rescue, we examined activity (TBS)‐dependent transcriptomic signatures. Analysis of TBS‐only slices demonstrated alterations in gene expression between WT_VEH_TBS and APP‐L/S_VEH_TBS mice. In particular, significant downregulation of genes in pathways known to be important for synapse function: axoneme, glutamatergic/GABAergic synaptic signaling, neurotransmitter release/transmission and neuronal action potential; and upregulation of gene pathways that are candidates contributing to degeneration in AD and in APP‐L/S_VEH_TBS mice: immune system processes, inflammatory responses, aging and neuron death; when compared to WT_VEH_TBS. Remarkably, the altered expression levels of most of the genes from these pathways were reverted to WT pattern in APP‐L/S_BD10‐2_TBS mice (Fig. 2), thus revealing candidate mechanisms to restore PPR and LTP deficits in APP‐L/S mice.ConclusionPTX‐BD10‐2 treatment mitigates Aβ‐related synapse dysfunction and alterations in synapse‐relevant gene expression profiles in APP‐L/S mice in the context of stimulation. These findings point to therapeutic potential of targeting TrkB/C, and moreover, provide a cellular model to identify candidate signaling modules for understanding synaptic impairment and revealing novel therapeutic targets.
Comparison of modifiable risk factors for dementia among rural and urban elderly adults: Data from two cohorts in India
Authors: Lingegodwa Abhishek Mensegere , Sundarakumar Jonas S , Hameed Shafeeq K Shahul , Ravindranath Vijayalakshmi 
Published: December 2021

AbstractBackgroundModifiable risk factors for dementia such as, diabetes, hypertension, dyslipidemia, hyperhomocysteinemia and lack of physical exercise contribute significantly to the etiology of dementia. SANSCOG and TLSA are prospective, community‐based cohort studies of aging population to identify risk and protective factors for cognitive decline and Alzheimer’s disease among individuals more than 45 years of age from rural Srinivaspura and urban Bengaluru respectively, in the state of Karnataka, India.MethodWe have recruited 1860 and 464 participants in SANSCOG (rural cohort) and TLSA (urban cohort) respectively. We calculated prevalence of modifiable risk factors and chi square test was used to determine group difference between both cohorts.ResultThe mean age and year of education in SANSCOG was 58.2years and 4.34years respectively, while in TLSA it was 66.6years and 16.3years.There was a statistically significant (p<0.001) difference in prevalence of chronic medical conditions between the groups with SANSCOG having low prevalence in hypertension, diabetes mellitus and hyperhomocysteinemia when compared to TLSA. However SANSCOG had high prevalence of dyslipidemia. The average metabolic equivalents (MET) as calculated from GPAQ for SANSCOG cohort was 5200, while it was 2500 for TLSA cohort.ConclusionThe rural cohort (SANSCOG) has less prevalence of hypertension, diabetes mellitus, and hyperhomocysteinemia, more physically active and higher prevalence of dyslipidemia when compared to urban cohort (TLSA).