bluuebunny/crossref_metadata_2025 huggingface dataset:
LANGaware: Leveraging machine learning on natural language for the early detection of neurodegenerative and psychiatric diseases
Authors: Rentoumi Vassiliki , Vassiliou Evangelos , Demiraj Admir , Pittaras Nikiforos , Mandalis Petros , Alexandridou Martha , Kemp Hollie , Eleftheriou Ioanna , Danezi Maria , Hatzopoulou Maria , Kamtsadeli Vasiliki , Paliouras George , Papatriantafyllou John D
Published: December 2021

Background

Various neurodegenerative and psychiatric diseases are related with changes in spoken language [1], although they have seldom been investigated. We evaluate the effectiveness of our language‐agnostic Machine Learning (ML) system to detect subtle changes in spoken language that manifest early signs of cognitive decline, thus assisting with its diagnosis. We evaluate our methodology using recordings of speech samples from multiple languages obtained from patient cohorts in early stages of cognitive decline and matched healthy controls.

Method

Our methodology involves capturing patient audio recordings while they are performing one or more predefined cognitive assessment tasks, involving, e.g., the description of a picture or recounting of an everyday activity. Afterwards, multi‐language audio recordings and generated transcripts are analyzed with audio and NLP feature extraction methods [3], ranging from semantic, morpho‐syntactic, phonological representations of the input, as well as, more sophisticated linguistic measures. The feature pool is filtered by a Pearson's rho threshold of 0.85. We build a Random Forest classifier out of 100 Decision trees, using the Gini impurity criterion, 5‐fold cross‐validation for training, elimination and composition‐based feature selection, as well as post‐selection retraining / fine‐tuning. The model's diagnostic performance is evaluated on a test set unseen during training.

Result

Our results are validated against the diagnosis that is provided by medical experts. Our performance in terms of accuracy (∼82%), f1 (84%) and ROC‐AUC score (∼82%) are clear indicators of the effectiveness of speech analysis towards detecting cognitive decline. Moreover, our tree‐based classifier produces probability scores that closely follow the proportion of pathological cases in the input data, with a correlation of 94%.

Conclusion

In the current evaluation we verified our conjectures regarding the strong capacity of speech to predict cognitive decline. Audio analysis and machine learning are proven to be invaluable tools in the prediction of early signs of cognitive decline, which are coupled with a wide spectrum of neurodegenerative and psychiatric diseases.

[1] Boschi, Veronica, et al., Frontiers in psychology 8 (2017): 269.

[2] Vassiliki Rentoumi et al., Alzheimer's & Dementia, Wiley, volume 16, 2020.

[3] Alberdi, Ane et al., Artificial intelligence in medicine 71 (2016): 1‐29.
Current management strategies: The DIAMOND‐Lewy toolkit
Authors: Taylor John‐Paul , Pillai Manjunadh
Published: December 2021

Background

Dementia with Lewy bodies (DLB) is a challenging condition to treat. People with DLB present with a range of cognitive, neuropsychiatric, sleep, motor, and autonomic symptoms. These symptoms can vary in severity between patients and fluctuate over time within an individual. Treating one symptom can led to the worsening of another and often symptoms are treated in isolation by different specialists leading to sub‐optimal care. The evidence base, particularly for pharmacological interventions is building and this is bolstered by an increasing evidence base in related conditions such as Parkinson's disease which have relevance for DLB. A way forward would be to provide a holistic symptom‐based management toolkit, inclusive of the existing evidence base and drawing upon consensus expert opinion.

Method

Taking a tri‐partite approach we 1) reviewed the existing evidence base in DLB 2) ran public‐patient workshops to identify best practice in DLB management based on lived experience 3) conducted a Delphi consensus process with a panel of experts in the field of Lewy body disease to determine best management practise. These activities led to the production of a holistic management toolkit which consisted of clinical summary sheets and detailed management guidelines. This toolkit was then trialled in a cluster randomized control study across 23 clinical services (e.g. memory clinics, movement disorders services etc.) in two UK regions, assessing the outcomes for patients and carers as secondary measures.

Result

The toolkit produced included 161 management statements covering a range of symptoms (cognitive, motor, neuropsychiatric, sleep and autonomic). In the trial 131 participants were recruited with 6 month data in 108 and provided preliminary evidence to suggest less marked patient deterioration on the global outcome measure (p<0.05) as well as improvements in care‐giver burden (p<0.01) and depression (p<0.05) in services using the toolkit compared to treatment as usual.

Conclusion

Developing a holistic management toolkit based on evidence base and expert opinion may have benefits for people living with DLB and their care‐givers.
Considerations for designing DLB trials
Authors: Armstrong Melissa J
Published: December 2021

Background

Dementia with Lewy bodies (DLB) is a common neurodegenerative dementia, but symptomatic and disease‐modifying treatments are lacking. Researchers designing clinical trials for DLB are faced with disease‐related challenges including choosing priority targets, populations, biomarkers, and outcomes.

Method

This presentation will review recent research relating to clinical trial design in DLB. Specific topics include research priorities of individuals living with DLB and caregivers, selecting the appropriate population for DLB trials (e.g. whether to combine with Parkinson disease dementia [PDD], subtyping based on presence of Alzheimer disease biomarkers), limitations of current outcome measures for use in DLB, and other challenges (e.g. fluctuations) inherent to DLB research.

Result

Individuals with DLB and caregivers identified research needs relating to determining the cause of DLB, improving diagnosis, investigating what to expect/disease stages, treating symptoms, identifying therapies to affect progression, and identifying approaches to improve daily function, quality of life, caregiving, and education. Determining whether to combine populations with DLB and PDD is challenging due to overlapping clinical and pathological features but also distinct experiences/trajectories and recruitment considerations. Recent research identified that disease‐modifying trials would use different endpoints for DLB versus PDD if prioritizing sample size. Research also demonstrated different trajectories in the face of Alzheimer disease co‐pathology, which is common in individuals with DLB. A systematic review of clinical outcome measures used in prior DLB trials identified the most common measures used to assess core DLB features in clinical trials. However, most of these outcome measures have limitations for use in DLB and no measure is specifically validated in DLB. Biomarker outcomes face challenges relating to lack of validation and DLB heterogeneity. The presence of fluctuations, the co‐existence of cognitive‐behavioral and motor symptoms, and limited specialty centers also challenge DLB trialists.

Conclusion

Individuals living with DLB identify a large number of research needs, but numerous challenges face individuals designing DLB trials. Researchers need to thoughtfully weigh DLB‐related decisions in trial design based on individual study goals. Further research is needed to optimize DLB trial design, including development/validation of outcome measures and novel trial approaches to account for challenges such as fluctuations and travel limitations.
Feasibility and acceptance of robotic care of Alzheimer’s disease and related dementia
Authors: Yuan Fengpei , Lopez Ruth Palan , Crane Monica , Montgomery Austin , Zhao Xiaopeng
Published: December 2021

Background

An estimated 44 million people worldwide live with Alzheimer’s disease and related dementias (ADRD). There is increasing interest in using emerging technologies such as robotics and artificial intelligence to provide assistance to people living with ADRD and their caregivers.

Method

We conducted an anonymous, online survey to study the public's attitude and acceptance of using a human‐like robot to assist people with ADRD. The survey was distributed via social media (e.g., Facebook, Twitter, LinkedIn), emails, and Listservs. Participants above age 18 were recruited to complete the survey. After informed consent, participants watched a brief (3 minute) video, which provided examples of how humanoid robots could be used to help people with ADRD. This was followed by questions, which took approximately 10 minutes to complete and assessed perceptions of the robot’s appearance and functions (e.g., companion, communication, providing entertainment, medication, emergence call). The participant could skip any questions that they do not wish to answer.

Result

Inputs to the survey were collected between November 13, 2020 and January 15, 2021. During that time, 1,004 people viewed the survey. The survey was started by 249 people from 16 different countries and districts (7 in Asia, 5 in Europe, 2 in North America, 1 in Oceania, and 1 in Africa). Ninety‐seven people dropped out before finishing all the questions and 152 people completed the survey. Among the complete responses, 11 persons reported to have dementia and 79 people had experience in providing care to ADRD patients. Among a list of robot’s functions, reminding to take medicine, making emergency call, and helping to contact medical services were rated as the most important by participants with dementia. Monitoring medication and making emergency communication/alert were rated as the most important by participants with experience in dementia caregiving.

Conclusion

The study presents statistical results from an anonymous online survey that collect international inputs on the use of social robots in Alzheimer’s care. Results of the survey show an overall positive attitude towards using humanoid robots for people with ADRD. Results may shed insight for design and development of assistive technology in robotics and AI for ADRD.
Disturbed sleep and reduced hippocampal integrity at midlife: Implications for AD risk in women with early surgical menopause
Authors: Gervais Nicole J , Brown Alana , Gravelsins Laura , Nicoll Gina , Sun Dorothy Leqi , Ge Jennifer Xiangning , Laird Kaz , Almey Anne , Reuben Rebekah , Karkaby Laurice , Duchesne Annie , Perovic Mateja , Gosselin Nadia , Grady Cheryl , Olsen Rosanna K , Einstein Gillian
Published: December 2021

Background

Women bear the greatest burden of Alzheimer’s disease (AD), and early (<45y) ovarian hormone deprivation via surgical menopause further increases risk (Rocca et al., 2007). Given that sleep disturbance is implicated in AD progression (Lim et al., 2013), an important area of investigation is determining whether younger women with early surgical menopause demonstrate disturbed sleep at midlife, and whether this may confer additional risks by contributing to changes in hippocampal integrity. Thus, we investigated whether middle‐aged women with bilateral salpingo‐oophorectomy not taking hormone therapy demonstrate sleep disturbance, and reduced hippocampal volume and memory. Additionally, we assessed whether sleep and hippocampal volume predict memory performance.

Method

Women with an early BSO that were either taking estradiol‐based hormone therapy (BSO+ET: age=43y; n=22), or not taking ET (BSO: age=46y; n=18) were recruited to the study, and were compared to age‐matched premenopausal (AMC: n=24) and spontaneously postmenopausal women who were ∼10y older (SM: 55y; n=20). Sleep was assessed via portable polysomnography (Vitaport‐5/REMbo‐234, Temec Technologies) for 1‐3 nights, and sleep staging was acquired using automated scoring (Z3score, Neurobit technologies). High‐resolution T2‐weighted scans were acquired using a Siemens 3T Prisma scanner, and hippocampal subfields (CA1, Subiculum, combined region: DGCA23), were manually segmented (Olsen et al., 2017) in FSLView. The interference match‐to‐sample (IMTS) task was used to asses and recognition memory for scenes (Watson et al., 2013).

Result

Both hormone‐deprived groups demonstrated increased sleep latency (BSOvsAMC: p<.05, d= 0.74; SMvsAMC: d= 0.69) and decreased sleep efficiency (BSOvsAMC: p<.05, d= 0.79; SMvsAMC: p<.05, d= 0.67). Only the BSO group demonstrated reduced volume in the anterior CA1 and DGCA23 relative to AMC (p<.05, d= 0.96‐1.06) and BSO+ET (p<.05, d= 0.67‐0.84). Additionally, the BSO demonstrated reduced efficiency (accuracy/RTcorrect) on scene recognition memory (p<.05, d=0.70‐0.86). Multiple regression analyses show that DGCA23 volume and group membership predict scene recognition memory performance.

Conclusion

While both hormone‐deprived groups demonstrated disturbed sleep, women with early BSO also showed reduced hippocampal integrity, despite being ∼10 years younger than SM women. These findings are consistent with the elevated AD risk among women with BSO. It remains to be seen whether sleep disturbance at a younger age exacerbates risk.
Increased cost of cognitive effort in preclinical Alzheimer’s disease
Authors: Aschenbrenner Andrew J. , Hassenstab Jason , Fagan Anne M. , Benzinger Tammie L.S. , Morris John C.
Published: December 2021

Background

Scores on neuropsychological tests depend on willingness to expend the necessary cognitive effort to complete each task. Group differences on cognitive test scores may partially reflect differences in perceived cognitive cost, or the willingness to exert cognitive effort, which will obscure estimates of “true” cognitive ability. It is critical, therefore, to obtain estimates of cognitive effort during neuropsychological testing. Subjective, questionnaire‐based measures of effort are prone to self‐report bias, so we administered an objective measure of cognitive effort (Cognitive Effort Discounting: COGED) to participants at the Knight ADRC. In COGED, participants complete increasingly difficult levels of a working memory task (the N‐Back) and then are asked to rate which “level” they would complete again for a given amount of monetary reward. We hypothesized that objective (COGED) but not subjective measures of effort would decrease in preclinical AD and this would be related to cognitive performance.

Method

Sixty‐five healthy older adults (Clinical Dementia Rating = 0) completed both the COGED task and a subjective effort rating scale (the NASA task load index). Participants were classified as amyloid‐positive (N=24) or negative (N=41) based either on amyloid PET scan or CSF Ab42/Ab40 ratio. Group differences on the effort task were analyzed using linear regression.

Result

Effort ratings decreased across levels of N‐back (p<0.001), indicating the task accurately tracks perceived effort. As expected, amyloid‐positive participants scored lower on the N‐back task (p=.03) but more importantly, they also scored lower on COGED than the amyloid‐negative group (Figure 1, p=0.05), after controlling for age, education and working memory. There were no group differences on the NASA (Figure 2). Surprisingly, neither COGED scores nor the NASA were related to performance on the N‐back, suggesting that effort ratings are independent of task performance.

Conclusion

We successfully adapted the COGED paradigm for remote assessment and administered the task to a group of healthy older adults from the Knight ADRC. This task accurately reflects effort / reward processing. Objective (but not subjective) measures of the ability to make these computations decline in preclinical AD but does not appear to affect concurrent cognitive assessments.
Loneliness experience through COVID‐19 pandemic and lockdown is related with resting‐state brain networks functional connectivity
Authors: Cabello‐Toscano María R. , Macià Dídac , Cattaneo Gabriele , Solana Javier , Abellaneda‐Pérez Kilian , Vaqué‐Alcázar Lídia , Tormos‐Muñoz Josep M. , Pascual‐Leone Alvaro , Bartres‐Faz David
Published: December 2021

Background

The reduction in social interactions often associated with old age frequently initiates or aggravates loneliness, increasing the risk of a number of diseases including depression and dementia (Mushtaq et al., JCDR. 2014;8(9):E01–WE4.). Loneliness has been related to particular patterns of brain resting‐state networks (RSNs; Spreng et al., Nat Commun. 2020;11(1):6393). However, the role of RSNs in a resilient response to reductions of social interactions remains unknown and the COVID‐19 pandemic provides a unprecedent opportunity to investigate it.

Method

Repeated loneliness assessments were collected by the Barcelona Brain Health Initiative (BBHI; www.bbhi.cat/en/) using the short UCLA Loneliness Scale (Russell et al., J Pers Assess. 1978; 42(3):290–294). Two timepoints were measured over two years prior to COVID‐19 outbreak and four thereafter (March, April, June and October 2020). We used baseline resting‐state functional magnetic resonance imaging (rs‐fMRI), from 281 participants (mean age 53.91±7.35; 137 women), acquired within 1‐2 years prior to the pandemic to compute resting‐state functional connectivity (rs‐FC) for each pair of nodes defined by the Schaefer‐Yeo atlas. Then, we utilized partial least squares (PLS) analysis for the decomposition of two multivariate sets (i.e., rs‐FC and loneliness scores) into latent variables of maximal covariation.

Result

We identified two latent trajectories significantly correlated with two latent connectivity patterns, each of them describing approximately opposite baseline rs‐FC and loneliness levels during the months with the most severe restrictions (i.e., March and April). The first latent trajectory showed greater baseline loneliness improving during the pandemic, associated with higher within‐network connectivity in the limbic and salience networks. The second trajectory captured individuals with baseline loneliness levels similar to the average population, improving in March, at the beginning of outbreak, and worsening in April, which was related to lower baseline within‐network connectivity in the DMN and higher in the dorsal attention and visual circuits.

Conclusion

Present findings reveal specific associations between RSNs’ functional connectivity and opposite changes in feelings of loneliness during an unanticipated period of severe social restrictions. Specifically, lower rs‐FC of limbic networks combined with high connectivity of salience system at baseline suggested greater resilience to the negative impact during the pandemic on loneliness.
Whose voices are still silent: Applying an intersectionality lens to existing evidence on cognitive impairment in older adults with combined hearing and vision impairment
Authors: Jaiswal Atul , Santhakumaran Sangeetha , Gupta Shikha , Dumassais Shirley , Aubin Gabrielle , Wittich Walter
Published: December 2021

Background

Age‐related sensory loss is a significant yet understudied public health problem. Evidence suggests that sensory loss in older adults is associated with an increased risk of cognitive impairment, functional decline, and social isolation. However, older adults with combined vision and hearing impairment (dual sensory impairment/DSI) are often overlooked in ageing as well as Alzheimer’s research. We synthesized existing evidence on cognitive impairment in older adults with DSI. Given the importance of diversity and inclusion in ageing and healthcare research, we applied the lens of intersectionality to the review data with the aim of exploring whose voices among older adults with DSI are not represented and whose voices are captured in the existing evidence.

Method

We conducted a scoping review using the methodological framework by Arskey and O’Malley (2005). The review considered empirical studies that explored cognitive impairment in older adults with DSI. The search was conducted across eleven scientific databases (CINAHL, Embase, Global Health, Mednar, OAIster, OpenGrey, PsycEXTRA, PsycINFO, PubMed, Web of Science, and WorldWideScience) in June 2020. Following the content analysis approach, the extracted data were later analyzed applying the intersectionality lens to capture attributes such as age, sex, gender identity, class, culture, disability, education, ethnicity, geography, indigeneity, and immigration status.

Result

Of 11,595 studies retrieved, fifty‐six (n = 56) were included in the review, demonstrating how limited the evidence is that exists on cognitive impairment among older adults with DSI. The majority of studies focused on older men with DSI from high‐income countries (Australia, Canada, Japan, Netherlands, UK, and the USA), with the exception of one study from India. Only a few studies reported binary gender differences, with no studies reporting cognitive impairment in gender diverse older population. Attributes such as immigration status and indigeneity were not reported, though the race and ethnicity of older adults were presented in some studies.

Conclusion

The review highlights important knowledge gaps related to cognitive impairment in older adults with DSI, which is a heterogeneous group. Researchers need to go beyond traditional approaches to promote the intersectionality paradigm in their research to provide evidence that is more representative and inclusive in nature.
Associations between social networks and cognitive declines in later life in longitudinal aging studies: A systematic review and meta‐analysis
Authors: Zhang Yun , Clouston Sean AP
Published: December 2021

Background

It remains unclear whether and how various aspects of social networks and cognitive declines are associated bidirectionally.

Method

We systematically searched the databases of PubMed, Web of Science and PsycINFO for longitudinal cohort studies that examined associations between social networks and cognitive declines in the general population up through February 2019. Characteristics of study designs, conclusions, and research trends were summarized. For meta‐analyses, estimates extracted from included studies were recalculated into odds ratios with 95% confidence intervals (95%CI). They were stratified by different classification criteria and pooled into random‐effect inverse‐variance weighted aggregations. Heterogeneity was tested by Q‐tests and I2 indexes. Publication bias was assessed by funnel plots and Egger’s tests.

Result

We identified 37 studies for systematic review and 24 for meta‐analysis. When researching effects of social network on subsequent cognitive decline, poor social networks were significant risk factors for cognitive declines (OR: 0.824, 95% CI: 0.769, 0.883; p<0.001; k=23) in longitudinal research. Stratified by social network characteristics, social network size (OR: 0.814, 95% CI: 0.663, 0.999; p=0.049; k=7), structure and function (OR: 0.879, 95%CI: 0.826, 0.936; p<0.001; k=17), and emotional feedback from network members (OR: 0.860, 95% CI: 0.652, 1.134; p=0.285; k=3) were all significant risk factors. When researching effects of cognitive declines on subsequent changes of social network, only a few studies (n=5) were included, which consistently supported that worse cognitive declines were associated with smaller size and less complex structure of social networks, however, their heterogeneous methods and study designs were not fit for meta‐analysis.

Conclusion

There are both significant effects of social networks on subsequent cognitive declines and significant effects of cognitive declines on changes of size and complexity of social networks in subsequent years. Most studies focused on effects of social networks on changes of social networks, only a few explored the opposite direction. The association between dynamic changes of social networks and cognitive declines is an under‐studied topic.
Late‐life social activity moderates the association between temporal lobe atrophy and episodic memory decline
Authors: Jo Jihyeon , Kim Hairin , Youm Yoosik , Chey Jeanyung
Published: December 2021

Background

Retirement and loss of important social relationships, including spouse and friends, make older adults more vulnerable to social isolation. Therefore, social activity could be important for older adults in maintaining life satisfaction and everyday functioning. Although several studies found protective roles of social activity against cognitive decline in late life, only a few studies examined the protective effects of social activity using longitudinal data. In this study, the effects of social activity on the relationship between brain aging and cognitive decline in older adults were examined during a four‐year period.

Method

Thirty‐two older adults with normal cognition (mean age = 70.69, SD: 6.27, mean education = 7.75, SD: 3.94 at baseline) were recruited from the Korean Social Life, Health, and Aging Project (KSHAP). Neuropsychological and brain imaging data, and social survey, were acquired in 2015 and 2019. Elderly Verbal Learning Test (EVLT) performance and cortical volumes from Magnetic Resonance Imaging (MRI) were the main measures of interest. The participants were asked to respond either “yes” or “no” to social survey items, including participation in community senior center events, volunteering for charities, religious activities, socializing events, leisure activities, and community activities. Social activity was explored in terms of level, consistency, and types of social activities. The Computational Anatomy Toolbox (CAT) was used to calculate temporal lobe gray matter volume selected as regions of interest (ROI) for its role in episodic memory. Hierarchical regressions were conducted to examine the effects of social activity on the relationship between temporal lobe atrophy and episodic memory decline.

Result

We found that the temporal lobe atrophy was associated with the delayed recall decline (r = 0.49, p = 0.003). More involvement in social activity at baseline decreased the effects of temporal lobe atrophy on delayed recall decline, controlling for age, sex, education, and self‐rated health as covariates. Further, consistent involvement in social activity, especially volunteering, attenuated the association between temporal lobe atrophy and delayed recall decline.

Conclusion

These findings suggest that social activities in late life function as cognitive reserve to buffer against the effects of temporal lobe atrophy on episodic memory decline in older adults.
Professional stress: A major risk factor in Alzheimer’s disease
Authors: Doscan Ana Maria M
Published: December 2021

Background

Early brain ageing (objectified by decreasing the age of onset of neurocognitive impairment) in the 35‐50 age segment has become a major concern for longevity medicine. Hence the need to extensively investigate chronic occupational stress and its effects on human brain, especially when acting as a risk factor for early Alzheimer’s disease. Preventive diagnosis of stress vulnerability, identification of demands that may exceed the individual's ability to respond effectively, quantification and objectification of stress, will help deceleration of early brain aging process.

Method

The study as designed to evaluate professional chronic stress that includes: history of stress in patients’ life, neurocognitive stress scales evaluation, biological evaluation of stress hormones ‐ urinary determination of serotonin, melatonin, adrenalin /noradrenalin, dopamine and salivary cortisol and measurement of heart rate variability.

Result

Our study results, based on the evaluation of 100 patients aged between 35‐65 years old, who work in stressful environment, show the link between elevated cortisol levels and the occurrence of clinical manifestations of neurocognitive impairment in the context of persistent occupational stress, and also the presence of depressive disorder in patients’ life history, in the context of changes in stress biomarkers.

Conclusion

Persistent professional stress can cause changes in the body's normal defense response to stress factors. Early identification of occupational stressors, clinical and biological knowledge of stress as well as the development of preventive and personalized measures, may define a future approach in the context of preventing stress induced pathologies like depression and anxiety, but also neurocognitive disorders (from mild cognitive impairment to early Alzheimer’s disease).
Racial differences in biomarkers of Alzheimer’s disease and inflammation
Authors: Hu William T. , Wharton Whitney , Parker Monica W.
Published: December 2021

Background

In clinically diagnosed Alzheimer’s disease (AD) dementia, older Black/African American (B/AA) adults were previously identified to have genetic risks, cognitive profiles, and longitudinal progression which differed from older White adults. Socioeconomic status and biological factors may each contribute to these findings. To determine if race modified biochemical as well as clinical AD phenotypes, we sought to analyze biomarker differences between B/AA and White adults across the aging spectrum.

Method

Three cohorts (n=237) were included in this Atlanta‐based study. We prospectively recruited people with normal cognition (NC, n=158) from community events across the greater Atlanta area, and people with mild cognitive impairment or AD dementia (MCI/AD, n=79) from the Emory Cognitive Neurology Clinic and the AD Research Center. Participants underwent detailed clinical, neuropsychological, CSF, and MRI analysis. CSF levels of AD biomarkers, neurofilament light (NfL), and seven cytokines were measured using Luminex in Atlanta with the exception that AD biomarkers for the middle‐aged cohort were measured using ELISA in Sweden.

Result

Compared to White adults with NC, B/AA adults showed reduced t‐Tau and p‐Tau181 levels across the aging spectrum by 25‐40%. This difference persisted in subjects with MCI/AD and after accounting for geographic socioeconomic conditions. CSF Aβ42 and NfL levels differed only according to diagnosis (NC vs. MCI/AD) but not race. Older B/AA adults also had lower CSF IL‐9 levels than older White adults, and AD‐associated alterations were only observed in B/AA. In keeping with this, neuropathologic and transcriptomic analysis showed race‐associated differences in the IL‐9 pathway.

Conclusion

B/AA adults had lower CSF levels of tau‐related protein than White adults across multiple cohorts, and different profiles of CSF and brain cytokine alterations in the presence of AD pathology. Distinct tau‐ and IL‐9‐related processes need to be further investigated according to genetic ancestry and cross‐generational social determinants of health.
Changes in subjective and objective cognitive decline in non‐depressed, non‐demented patients with Parkinson's disease: A 1 to 2 years’ follow‐up
Authors: Rattanabannakit Chatchawan , Wongkanjana Nutchaphol , Munjit Rabwas , Warunyuwong Wikrom , Srivanitchapoom Prachaya , Senanarong Vorapun
Published: December 2021

Background

Subjective and objective cognitive impairments were prevalent in patients with Parkinson’s disease (PD), but there is no data on longitudinal cognitive change in these patients in Thailand. We aimed to evaluate the cognition, perception of cognitive decline, and the diagnosis of cognitive impairment in Thai patients with PD after 1‐2 follow‐up.

Method

Non‐demented, non‐depressed PD patients were included from the Movement Disorder Clinic at Siriraj Hospital. Patients with severe motor symptoms that interfered with cognitive tests were excluded. We used the Montreal Cognitive Assessment‐Thai version (MoCA) to assess cognition. Perception of cognitive decline was assessed by using the Cognitive Change Index (CCI) rated by patients (CCI‐S) and their informants (CCI‐I). All parameters were assessed at baseline and re‐evaluated at 1‐2 years. Association of MoCA, CCI‐S, CCI‐I, the discrepancy of CCI (CCI‐D; CCI‐S minus CCI‐I), apathy score, and patients’ clinical characteristics were analyzed.

Result

Sixty‐two participants were followed for 18.59±4.55 months. The mean age at baseline was 63.38±9.63 years, and the mean duration of PD diagnosis was 5.63±3.49 years. The MoCA score slightly declined from 20.6±5.1 at baseline to 20.1±4.9 (mean changes ‐0.53±3.2, p=0.195). 47.1% of patients with normal cognition at baseline converted to PD‐MCI. Most (77.8%) PD‐MCI patients remained in the MCI stage, 11.1% turned to dementia, and 11.1% reverted to normal. The CCI‐I and apathy scores increased significantly after 1‐2 years (p=0.003 and <0.001, respectively), but not the CCI‐S. After controlling with age, gender, and education, the 14‐item Starkstein Apathy Scale score at follow‐up was significantly associated with the CCI‐I and the MoCA scores (r = 0.37 and ‐0.34, respectively, both p<0.01). Moreover, change in MoCA scores was significantly associated with the score of CCI‐D at follow‐up (r=‐0.29, p=0.03). Participants with orthostatic hypotension had a lower MoCA score at follow‐up (p=0.04).

Conclusion

Apathy, informant perception of cognitive decline, but not the cognition, were changed significantly in non‐demented PD patients after 1‐2 years follow‐up. Apathy, the discrepancy of perception of cognitive decline between participant and informant, and orthostatic hypotension may be related to the lower cognition at follow‐up. Further studies with a larger sample size and more extensive neuropsychological evaluation are required.
Association between cerebral small‐vessel disease and Alzheimer’s disease pathologies
Authors: Cai Yuan , Mok Vincent C.T. , Liu Wanting , Fan Xiang , Shi Lin , Au Lisa W.C.
Published: December 2021

Background

Controversy exists regarding the etiological role of cerebral small vessel disease (CSVD) in Alzheimer's disease (AD). We thus evaluated the association between brain Aβ/tau burden and white matter hyperintensity (WMH) volume among subjects with varying severity levels of cognitive impairment.

Method

A total of 84 stroke‐free subjects (healthy controls [HC]=10; subjective cognitive decline [SCD]=32; mild cognitive impairment [MCI]=26; dementia =16) were included. All patients underwent structural MRI, 11C‐ PIB, and 18F‐T807 PET to measure CSVD makers, Aβ deposition (A+) and pathologic tau (T+), respectively. WMH volume was quantified by automatic segmentation using AccuBrain® IV 1.1 (BrainNow Medical Technology Company Ltd.).

Result

No significant association was found between A+T+ and WMH volume in the overall population (β =‐0.03 ;95% CI, ‐0.04‐0.11; p=0.10). There was also no significant association found within different cognitive diagnostic group except in those with dementia, where we found that increasing global 11C‐ PIB SUVR correlated with lower WMH volume (B=‐1.76 ;95% CI, ‐2.92‐ ‐0.59; p=0.007). No significant association between 18F‐T807 SUVR and WMH volume was observed

Conclusion

We found no association between brain Aβ/tau burden and WMH volume except an inverse association was noted between Aβ and WMH in dementia patients. PiB retention might be restrained by WMH in those patients with higher CSVD burden.
Physical activity attenuates or even eliminates the risk of all‐cause dementia associated with aging in older adults: A population‐based cohort study
Authors: Feter Natan , Leite Jayne S , Rombaldi Airton
Published: December 2021

Background

From 2016 to 2040 the number of people with all‐cause dementia in the United Kingdom is expected to increase by 57%, while 70% percent of it is due to a higher life expectancy. It is meaningful to examine whether physical activity could mitigate the risk of all‐cause dementia associated with aging in older adults. We aimed to examine the overall and age‐stratified effect of physical activity on the risk of all‐cause dementia in older adults.

Method

Older adults aged 50 or more participants of the English Longitudinal Study of Aging (ELSA) were followed during a 17‐years follow‐up, between 2002 and 2019. Physical activity was accessed using a self‐reported, validated questionnaire in each wave (2002‐2019). Participants were classified as inactive, low, or moderate‐to‐high levels of physical activity. Medical diagnosis of dementia was asked in each wave for either the cohort member or by a proxy interview with family or caregivers. Additionally, the Informant Questionnaire on Cognitive Decline in the Elderly was used to determine the presence of all‐cause dementia (cut‐off = 3.5).

Result

Data from 8,270 older adults were analyzed (55.6% women; mean [SD] age, 63.9 [9.7]). Over a 17‐year follow‐up, 7.8% (95%: 7.3 to 8.4) were diagnosed with all‐cause dementia. For each year increased in age, the odds of all‐cause dementia increased 6.1% (95%CI: 5.1% to 7.1%). On the other hand, participants engaging in low (OR: 0.27; 95%CI: 0.22 to 0.33) or moderate‐to‐high level (OR: 0.12; 95%CI: 0.09 to 0.16) of physical activity had lower odds of incidence of all‐cause dementia through the follow‐up period. Participants aged 80 or over who engaged in a moderate‐to‐high level of physical activity had a lower risk of all‐cause dementia than inactive adults aged between 50‐69 years. Results were sustained after sensitive analysis to reduce the impact of reverse causality.

Conclusion

Although aging is the strongest risk factor for all‐cause dementia, physical activity could eliminate the risk associated with aging in older adults. Public health policies should consider that for older adults, engaging in physical activity below recommended levels may be an accessible and achievable strategy to prevent all‐cause dementia.
Exercise training improves cognition in chronic stroke: A 6‐month randomized controlled trial
Authors: Liu‐Ambrose Teresa , Falck Ryan S , Best John R , Hsiung Ging‐Yuek Robin , Middleton Laura E , Hall Peter A , Davis Jennifer C , Eng Janice J
Published: December 2021

Background

A stroke doubles one’s risk for dementia. Impairment in multiple domains of cognition are common following stroke. Thus, stroke survivors represent a target population in need of intervention strategies to promote cognitive function and prevent dementia. We assessed whether targeted exercise training or cognitive and social enrichment activities would promote cognitive function in community‐dwelling adults with chronic stroke (i.e., > 12 months since stroke event).

Methods

A three‐arm parallel, single‐blinded, 6‐month randomized controlled trial with 120 adults with chronic stroke who were randomized (2:2:3) to: 1) targeted exercise training (EX; n=34)) modeled after the Fitness And Mobility Exercise (FAME) program (Eng, Top Geriatr Rehabil, 2010); 2) cognitive and social enrichment activities (Cog‐Plus; n=34); and 3) an active control group (CON; n=52). Each experimental arm was group‐based and 2x/week. The primary outcome was the ADAS‐Cog‐Plus, a global measure of cognitive performance using multidimensional item response theory to summarize scores from the 13‐item ADAS‐Cog and other standard cognitive assessments (i.e., Trail Making Test Parts A and B, Digit Span Forward and Backward, and Animal and Vegetable Fluency). Lower ADAS‐Cog‐Plus scores represent better cognitive performance; ADAS‐Cog‐Plus scores of approximately −1.0 indicate healthy cognitive performance, 0.0 indicate mild cognitive impairment, and 1.0 indicate dementia. The primary analysis using linear mixed model compared changes in ADAS‐Cog‐Plus performance from baseline to month 6, with baseline ADAS‐Cog‐Plus and Mini‐Mental State Examination scores as covariates. Two planned simple contrasts (i.e., EX vs. CON; Cog‐Plus vs. CON) were performed using the Dunnett test.

Result

Mean baseline Fugl‐Meyer score was 81.21 (SD=23.85; range: 6‐100) and mean baseline Montreal Cognitive Assessment score was 21.89 points out of 30. An overall attrition rate of 14% was observed (EX=6; Cog‐Plus=5; CON=6). Participants in the EX group had significantly better ADAS‐Cog Plus performance than CON at trial completion (estimated mean difference: ‐0.23; 95%CI:[‐0.43, ‐0.03]; p=.024). There was no significant difference in ADAS‐Cog Plus performance between the Cog‐Plus and CON group at trial completion (estimated mean difference: ‐0.10; 95% CI:[‐0.30, 0.10]; p=.314).

Conclusion

Targeted exercise training may be efficacious in improving cognition in adults with chronic stroke and should be promoted among individuals with chronic stroke.
Using amyloid PET as a biomarker to detect progression of early Alzheimer’s disease
Authors: Ali Muhammad , Farias Fabiana H.G. , Sung Yun Ju , Wang Fengxian , Cruchaga Carlos
Published: December 2021

Background

Alzheimer’s disease (AD), the most common form of dementia, is a complex polygenic disease with genetic, cellular, pathologic, and clinical heterogeneity. Recently, significant attempts have been made for identifying AD biomarkers for reliably tracking disease progression in its early asymptomatic stages. To this end, amyloid imaging technique has provided a breakthrough in deciphering the pathophysiology and accumulation of amyloid beta (Aβ) and hyperphosphorylated tau deposits in the brain. As such, our lab and multiple other research groups have used biomarker levels such as CSF Aβ tau, TREM2, and amyloid positivity for genetic association studies and identified novel genes and loci associated to AD. In a recent study, Raghavan et al., analyzed 4,314 participants and identified a novel locus for amyloidosis within RBFOX1 gene, however, this finding has not been replicated yet.

Method

In order to investigate the underlying genetic basis for brain amyloidosis in AD, we aim at systematically analyzing the largest collection of amyloid imaging (N=6,243), data across multiple ethnicities from multicenter cohorts (ADRC, A4, DIAN, ADNI, and ADNIDOD) as a quantitative trait to identify the functional variants and genes driving the association of AD.

Result

Results and key findings will be presented at the AAIC meeting.

Conclusion

We will leverage these datasets to generate prediction models for amyloid positivity and Mandelian Randomization (MR) analyses. Furthermore, the identification of AD‐specific molecular signatures and pathways will enable the characterization of appropriate therapeutic targets for the prevention and/or treatment of AD.
Effect of intensive blood pressure reduction for the prevention of cognitive decline and dementia: A systematic review and meta‐analysis
Authors: Dallaire‐Théroux Caroline , Quesnel‐Olivo Marie‐Hélène , Brochu Karine , Bergeron Frédéric , Laforce Robert , Verreault Steve , Camden Marie‐Christine , Duchesne Simon
Published: December 2021

Background

High blood pressure is a treatable, high risk factor for both cerebrovascular disease and cognitive impairment. Antihypertensive treatment can be viewed therefore as a potential approach to reduce dementia risk. We aimed to examine the effectiveness and safety of intensive, as opposed to standard, blood pressure reduction in adults with hypertension for the primary or secondary prevention of cognitive decline and dementia.

Methods

We conducted a systematic review and meta‐analysis of randomized controlled trials reporting on intensive versus guideline blood pressure targets and cognitive outcomes by searching MEDLINE (Ovid), Embase (Embase.com), CENTRAL, Web of Science, CINAHL, PsycINFO (Ovid), ICTRP and ClinicalTrials.gov databases up to October 27, 2020. Titles and abstracts screening, full‐texts review, data extraction, and risk of bias assessment were performed in duplicates. Conflicts were resolved by an independent reviewer. Our primary outcome was cognitive decline from baseline. Secondary outcomes included incidence of dementia, mild cognitive impairment, cerebrovascular events, serious adverse events, and mortality.

Results

We identified five trials (17,396 participants), reported in fourteen publications meeting our inclusion criteria among 7,755 screened citations. The mean follow‐up duration was 3.3 years (range 2.0 to 4.7 years). Intensive blood pressure reduction was not associated with a significant change in global cognitive performance at follow‐up (SMD 0.01, 95% CI ‐0.04 to 0.06), incidence of dementia (RR 1.09, 95% CI 0.32 to 3.67) or incidence of mild cognitive impairment (RR 0.91, 95% CI 0.73 to 1.14) when compared to standard treatment. However, we found a significant reduction of cerebrovascular events in the intensive treatment arm (RR 0.79, 95% CI 0.67‐0.93), with no increased risk of serious adverse events (RR 1.13, 95% CI 0.91‐1.40) or mortality (RR 0.93, 95% CI 0.75‐1.15).

Conclusions

We found insufficient evidence to justify more intensive blood pressure reduction for the prevention of cognitive decline and dementia in adults with hypertension. Prospective, randomized trials with longer follow‐ups may be necessary to highlight such potential benefits.
Emotion characteristics of older adults with MCI among a socially isolated cohort using NIH toolbox: I‐CONECT Study
Authors: Yu Kexin , Wild Katherine , Silbert Lisa C , Kaye Jeffrey A , Dodge Hiroko H
Published: December 2021

Background

A diagnosis of Mild Cognitive Impairment (MCI) has been found to be associated with changes in emotional wellbeing and social relationships. Socially isolated older adults with MCI are at greater risk of developing Alzheimer's Disease and Related Dementias. Better understanding the emotional functioning of individuals with MCI could inform the development of behavioral health interventions. Within a socially isolated sample of older adults, this study compares psychosocial wellbeing of older adults with MCI to their cognitively normal counterparts.

Methods

This cross‐sectional study uses baseline data from the Internet‐based Conversational Engagement Clinical Trial (I‐CONECT, ClinicalTrials.gov: NCT02871921). Eligible participants were ages 75 or older and were socially isolated as defined by scoring <12 on the 6‐item Lubben Social Network Scale, engaging in conversations lasting 30 minutes ≦ twice per week, or answering "Often" to at least one question of the three‐item UCLA Loneliness Scale. MCI status was determined according to clinical diagnosis. This working sample includes the first 127 participants whose baseline emotion battery scores were available as of November 2020. Based on NIH Toolbox scoring instructions, three domain scores were calculated with the 17 emotion measures, i.e., negative affect, social satisfaction, and psychological wellbeing. Linear regressions were conducted for all 17 Emotion Battery measures and 3 domain scores, controlling for age, gender, education, and severe depressive symptoms. Severe depressive symptom was operationalized as scored ≧5 on the 15‐item Geriatric Depression Scale (GDS).

Results

Participants' mean age was 81.1 (SD=4.6); 69.9% of the participants were female; and mean years of education was 15.2 (SD=2.3). 54% of the participants were diagnosed with MCI. The average GDS score was 2.3 (SD=1.8). For the three major emotion domains assessed, older adults with MCI had more negative affect, yet no difference was observed in social satisfaction and psychological wellbeing (see Table 2). More specifically, compared to cognitively normal older adults, individuals with MCI had higher levels of fear, perceived hostility, perceived stress, sadness, and lower self‐efficacy.

Conclusion

The study's findings indicate that older adults with MCI experience more negative emotions than cognitively normal older adults. However, there were no between‐group differences observed in positive emotions.