bluuebunny/crossref_metadata_2025 huggingface dataset:
Modifications in response to the COVID‐19 pandemic in a multimodal intervention trial to prevent cognitive impairment in older women with cardiovascular disease
Authors: Halloway Shannon , Arvanitakis Zoe , Wilbur JoEllen , Schoeny Michael E , Barnes Lisa L , Pressler Susan J , Gamboa Charlene , Knudson Krista , Borgia Jeffrey A , Volgman Annabelle Santos
Published: December 2021

Background

Cognitive impairment disproportionately affects women compared to men, and cardiovascular disease (CVD) increases risk. Physical activity and cognitive training may have synergistic effects on cognition when delivered together. However, no multimodal intervention has targeted older women (≥65) with CVD or has utilized a scalable lifestyle approach. Our study seeks to evaluate the efficacy of MindMoves, a 24‐week multimodal intervention, on cognition and serum biomarkers in 254 older women with CVD. However, effects of the COVID‐19 pandemic complicated implementation of our original in‐person trial protocol. The purpose of this paper is to describe protocol modifications made by our interdisciplinary team in response to COVID‐19,

Method

We employ a 2x2 factorial randomized controlled trial design to determine independent and combined efficacies of Mind (cognitive training with BrainHQ) and Move (lifestyle physical activity with goal self‐monitoring and nurse‐led group meetings) interventions. Outcome measures of cognition and serum biomarkers (brain‐derived neurotrophic factor, vascular endothelial growth factor, insulin‐like growth factor 1) are collected at baseline, 24, 48, and 72 weeks. Nurse scientists oversee interventions, cardiologists refer women ≥65 years with CVD and no cognitive impairment from clinics, and a cognitive neurologist and neuropsychologist oversee outcome measures. Pandemic‐related protocol changes were implemented to maximize study integrity and participant/staff safety. Targeted mailings were added to in‐person recruitment strategies. Screening activities shifted to phone. In‐person data collection was modified for phone/virtual settings, including accelerometer mailing (device measure of physical activity), neurocognitive tests validated for phone use, and home‐based participant‐administered dried blood spot collection for serum biomarkers. Women are now provided and trained to use iPad tablets to complete intervention activities virtually (e.g., Move group meetings).

Result

The anticipated number of participants (19) in the first cohort was recruited without disruption, in the original timeline. Participants completed all phone‐based questionnaires and mailed devices were returned. Randomization occurred as planned. Intervention activities are ongoing, including phone‐based orientations and ≥90% attendance at virtual meetings.

Conclusion

The modified trial protocol is being successfully implemented during the COVID‐19 pandemic. Results will demonstrate efficacy of pivoting from in‐person to virtual delivery of a lifestyle‐focused multimodal intervention in at‐risk older women with CVD.
Social support factors and cognitive outcomes in mid‐life
Authors: Bruck Margaret , Xia Feng , Dintica Christina S. , Sidney Stephen , Yaffe Kristine
Published: December 2021

Background

A growing body of evidence suggests that social support is associated with cognitive outcomes including dementia in late‐life. Yet few studies have examined the association between social support and cognition in mid‐life, a critical time of transition to aging. Furthermore, little is known about the effects of other aspects of social function such as emotional support, social strain and loneliness on cognition. Our goal was to investigate the association between several social support factors and cognitive performance in mid‐life.

Method

We studied 2,732 Black and White adults from the Coronary Artery Risk Development in Young Adults (CARDIA) Study who completed a social support questionnaire at baseline (CARDIA Year 20, mean age 45.2 years, 57% female, 45% Black) which assessed aspects of emotional support, social strain, and loneliness. At the 10‐year follow‐up, cognitive performance was evaluated with a battery of five tests: Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), Stroop Test, Verbal Fluency (category and letter fluency), and the Montreal Cognitive Assessment (MOCA) and standardized to z‐scores. We used linear regression to determine the association between emotional support, social strain, and loneliness, categorized as tertiles (comparing high to low), with mid‐life cognition.

Result

In unadjusted models, all three social support factors were associated with cognition 10 years later. After adjusting for age, sex, race, education, marital status, income, and depression, participants reporting higher levels of emotional support performed better on all cognitive tests (DSST High vs. Low (z‐score)=0.13 [95%CI 0.03, 0.23]; RAVLT=0.17 [95%CI 0.07, 0.27]; reverse Stroop=0.15 [95%CI 0.05, 0.26]; Verbal Fluency=0.12 [95%CI 0.01, 0.23]; MOCA=0.19 [95%CI 0.09, 0.28]). Less social strain was associated with higher scores on most tests (DSST Low vs. High=0.16 [95%CI 0.06, 0.26]; RAVLT=0.11 [95%CI 0.01, 0.21]; and MOCA=0.13 [95%CI 0.04, 0.23]). Loneliness was not associated with mid‐life cognition.

Conclusion

Greater level of social support, particularly emotional support, was associated with better mid‐life cognitive outcomes 10 years later. To better inform risk and prevention efforts, more research should be conducted to investigate the associations between various dimensions of social support and cognitive outcomes across the life course.
Brain age acceleration as biomarker of Alzheimer’s disease progression: Functional network connectivity analysis
Authors: Sendi Mohammad S.E. , Salat David H , Calhoun Vince D
Published: December 2021

Background

The brain age gap, the difference between an individual’s brain predicted age and chronological age, is used as a brain disease biomarker and aging. To date, although previous studies utilized mostly structural magnetic resonance imaging (MRI) data to predict brain age, less work has used functional network connectivity (FNC) from resting‐state functional MRI (rs‐fMRI) to indicate brain age and its link with Alzheimer’s disease (AD) progression. This study aims to estimate brain age from FNC and introduce it as a biomarker of AD progression.

Method

This study used 1091 rs‐fMRI data and the chronological age at the time of scanning, ranging from 42‐95, from the Open Access Series of Imaging Studies (OASIS)‐3 cohort. This dataset includes 1021 healthy subjects (HC) and 70 AD patients. We used group independent component analysis to estimate 53 components for the whole‐brain. Then, FNC feature, in total 1378, of each subject was calculated by applying the Pearson correlation. A support vector regression (SVR) was trained on 951 HC subjects in which FNC features and the chronological age was served as predictor and prediction output, respectively. We then tested the trained model on 70 HC (age mean± sd: 73.66± 7.47) and 70 AD (age mean± sd: 73.34± 7.51) subjects to predict their brain age.

Result

The correlation between predicted brain age and the chronological age of HC test data was R=0.73, (p=5.3e‐13, N=70), while the correlation between predicted brain age and AD patients' chronological age was R=0.33 (p=0.004, N=70). This result shows that the model based on HC could better predict the HC age than the AD patients. The brain age gap mean and standard deviation for the test HC and AD group was ‐2.2581± 5.0879 and 2.0814± 7.4520. This result shows that the brain age gap was increased in AD (Cohen’s d=0.68, p<0.001).

Conclusion

We proved that FNC, estimated from rs‐fMRI, could predict the brain age in HC. Also, we found an acceleration in the brain predicted age of AD patients. We also found that the AD subjects' brain age gap was significantly higher than the brain age gap of the HC group.
Intracranial stenosis interacts with amyloid positron emission tomography (PET) standard uptake value ratio (SUVR) to predict cognitive decline in a memory clinic cohort
Authors: Lim Mervyn Jun Rui , Gyanwali Bibek , Chen Christopher , Hilal Saima
Published: December 2021

Background

Intracranial stenosis (ICS) is associated with cognitive impairment and dementia. However, data examining the effect of ICS and beta‐amyloid on cognitive decline are lacking. Thus, we aimed to investigate the effect of ICS on beta‐amyloid and their interaction on cognition in a memory clinic cohort.

Methods

Participants were recruited from the National University Hospital memory clinic in Singapore. Data was collected using a standardized questionnaire, physical examination and 3T MRI. ICS was defined as arterial narrowing that exceeded 50% of the luminal diameter in any of the intracranial vessels. Beta‐amyloid was measured using [11C]‐PiB‐PET global standardized uptake value ratio (SUVR). Cognition was assessed by neuropsychological testing.

Results

185 participants diagnosed with no cognitive impairment, cognitive impairment no dementia, or dementia were included. The mean age was 75.7 ± 7.3 years and 86 (46.5%) participants were male. A total of 17 (9.2%) participants had ICS and the mean SUVR was 1.4 ± 0.4. In adjusted models, ICS was not significantly associated with elevated SUVR in the overall population (β = ‐0.04; 95%CI = ‐0.24 – 0.16; p‐value = 0.69). In adjusted models, ICS had significant interaction with SUVR in global cognition (p = 0.043), attention (p = 0.024), visual memory (p = 0.019), and visuospatial function (p = 0.047). In patients with no ICS, SUVR was associated with worse cognitive scores, while in patients with ICS, SUVR was associated with better cognitive scores. This interaction remained significant for attention (β [No ICS]: ‐1.57 [95%CI: ‐2.50 to ‐0.63]; β [Yes ICS]: 1.42 [95%CI: ‐1.13 to 3.96]; p = 0.029) and visual memory (β [No ICS]: ‐1.57 [95%CI: ‐2.38 to ‐0.76]; β [Yes ICS]: 1.04 [95%CI: ‐1.17 to 3.24]; p = 0.028) even after further adjustment for ApoE and hippocampal volume.

Conclusion

In patients with no ICS, beta‐amyloid was associated with worse cognition, while in patients with ICS, beta‐amyloid was associated with better cognition. This suggests that beta‐amyloid may have a protective effect against cognitive impairment in patients with ICS. Further studies are required to investigate this association and elucidate on the mechanistic pathway of the interaction between ICS and beta‐amyloid on cognition.
Integration of health information technology and promotion of personhood in family‐centered dementia care
Authors: Brown Ellen L , Ruggiano Nicole , Roberts Lisa , Clarke Peter J , Davis Debra J , Hough Monica Strauss , Muñoz Mariateresa (Teri) H , Framil C Victoria , Allala Sai Chaithra
Published: December 2021

Background

Alzheimer’s disease and related dementias (ADRD) are leading causes of disability and often result in communication deficits that can complicate ADRD caregiving and clinical care. Augmentative and Alternative Communication (AAC) devices have been shown to provide assistance in communication for persons with ADRD, although many of these devices have been criticized for limited ability to customize content or design, and not addressing the impact of communication deficits on the larger family unit. This program of research has been informed by related theoretical frameworks: person‐centered (PCT) and family‐centered theories (FCT).

Method

An interdisciplinary team working with stakeholders are designing a novel information technology prototype with a touchscreen to promote communication and personhood for persons with ADRD. This improved ACC device is best described as an AAC Plus. The AAC Plus goes beyond traditional AAC in that it can be integrated into an existing healthcare delivery system and provide real‐time clinical data and health trends to the healthcare provider for early detection, intervention, and monitoring of clinical symptoms. In addition, the AAC Plus: (1) is designed to promote engagement and communication for interactions between the caregiver and person with ADRD using ubiquitous touchscreen technology; (2) facilitates tracking of behavioral and other clinical information about the person with ADRD, such as sleep and appetite; (3) has easily customizable interfaces for the caregiver and person with ADRD.

Result

Usability and feasibility will be tested using common use case scenarios, user experience testing, alpha testing, and beta testing methodologies to evaluate ease‐of‐use and cognitive ergonomics for both caregivers and persons with ADRD. This will include evaluating the design layout, user flow, and integrated content for the device’s interfaces. Once usability and feasibility is established, the team will conduct a randomized trial of the AAC Plus, in collaboration with Memory Centers in the United States (R01 AG068572‐01).

Conclusion

This presentation will provide content on the process of development and human‐computer interaction methodologies used to develop an evidence‐based, innovative technology for people with ADRD and their caregivers. Attention will also be given for developing technologies for ADRD care that integrate person and family‐centered design.
The association between isolated hypertension and brain volumes in UK Biobank
Authors: Newby Danielle , Winchester Laura M , Sproviero William , Fernandes Marco , Ghose Upamanyu , Li Qingqin S , Launer Lenore J , Nevado‐Holgado Alejo J
Published: December 2021

Background

Hypertension is a well‐established risk factor for cognitive impairment, brain atrophy and dementia. Isolated hypertension is where either systolic or diastolic blood pressure is high and the other measure is normal. It is unknown the impact of isolated hypertension on brain atrophy and how it compares to non isolated hypertension (NIH). Therefore it is important to investigate the impact of isolated hypertension to help understand its impact on future dementia risk and cognitive decline. We investigated relationships between isolated hypertension on brain volumes using the largest cohort of healthy individuals from the United Kingdom.

Method

Using the UK Biobank cohort, we carried out a cross‐sectional study using 31,513 participants [mean age 63 years, 53% female] with BP measurements and brain MRI data. We used linear regression models to determine the associations between isolated systolic (ISH) and isolated diastolic hypertension (IDH) split by BP medication use with brain volumes (total volume, total grey matter, hippocampal and white matter hyperintensities (WMH)).

Result

Individuals with ISH and taking BP medications (n = 3137) had smaller grey matter volumes (β = ‐0.04 [95%CI ‐0.07 to ‐0.03]), and greater WMH (β = 0.25 [95%CI 0.21 to 0.28]) compared to normotensive individuals (n = 14677). Interestingly, individuals with IDH and taking BP medications (n =140) also had smaller total grey matter (β = ‐0.11 [95%CI ‐0.19 to ‐0.04]) and larger WMH (β = 0.26 [95%CI 0.12 to 0.41]). Individuals with ISH have comparable total grey matter atrophy to individuals with NIH not taking medications (ISH β = ‐0.044 vs NIH β = ‐0.027) and have comparable WMHs (ISH β = 0.25 vs NIH β = 0.022).

Conclusion

Our results indicate that individuals with isolated hypertension have greater total grey matter atrophy and vascular pathology and this atrophy is similar to certain subsets of individuals with non isolated hypertension. These results provide a further emphasis of preventative strategies particularly focusing on isolated systolic hypertension as well as non isolated hypertension in maintaining brain health to reduce dementia risk earlier in life.
Association of psychological stress with risk of dementia: A systematic review and meta‐analysis
Authors: Franks Katherine H , Bransby Lisa , Saling Michael M , Pase Matthew P
Published: December 2021

Background

With no effective disease‐modifying treatments, there is a need to identify lifestyle risk factors that may prevent or delay the onset of dementia. One proposed risk factor is psychological stress. Although many studies have investigated the association between stress and dementia, to our knowledge, no meta‐analysis has examined this. The current study investigated the association between different aspects of psychological stress (including neuroticism, stressful life events and perceived stress) and the risk of incident dementia in adults without cognitive impairment.

Method

The study was prospectively registered and conducted in accordance with PRISMA guidelines. PsycINFO, Embase and MEDLINE were searched for eligible observational, prospective studies from database inception to October 2020. Pooled hazard ratios (HRs) were generated using random‐effects models to separately examine each aspect of stress in relation to the incidence of all‐cause dementia and Alzheimer’s disease (AD) dementia.

Result

Of the 1607 studies screened, 15 (18 cohorts) were included in meta‐analyses. Across studies, higher perceived stress was significantly associated with an increased risk of all‐cause dementia (Cases/Total N = 203/1,882: hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.07‐1.95). Exposure to two or more stressful life events (versus none) was also significantly associated with an increased risk of all‐cause dementia (Cases/Total N = 3,352/11,597: HR = 1.72, 95% CI = 1.14‐2.60), while one or more stressful life events was not. Higher neuroticism was significantly associated with an increased risk of AD dementia (Cases/Total N = 497/4,771: HR = 1.07, 95% CI = 1.01‐1.12), but not all‐cause dementia.

Conclusion

Psychological stress in adulthood is associated with an increased risk of dementia. Further research is needed to clarify the mechanisms underlying these associations.
Are we targeting the right population? Application of eligibility criteria of 10 dementia prevention trials to the general population
Authors: Licher Silvan , Wolters Frank J , Pavlović Jelena , Kavousi Maryam , Leening Maarten JG , Ikram M Kamran , Ikram M Arfan
Published: December 2021

Background

Various trials have investigated the effects of multidomain lifestyle interventions on cognitive decline, but with limited clinical benefit. This could be due to these trials targeting older individuals with elevated cardiovascular risk factors, who often already qualify for preventive intervention. We aimed to determine clinical implications of trials by application of trial eligibility criteria and prognosis to the general population.

Method

We conducted a literature review and sought to identify large (≥500 participants), phase‐3 multidomain lifestyle trials for the prevention of cognitive decline or dementia. We extracted eligibility criteria, and applied these to participants from the population‐based Rotterdam Study (40≥years). We determined what proportion of trial‐eligible individuals qualified for preventive intervention according to American (ACC/AHA) and European (ESC/EAS) cardiovascular prevention guidelines. To evaluate whether trial inclusion criteria optimally captured individuals at high risk of dementia that could benefit most, we compared remaining lifetime dementia risk, with 10‐year predicted risks for cardiovascular events.

Result

Out of 1448 abstracts, we five identified published dementia prevention trials (DR’s EXTRA, FINGER, preDIVA, MAPT and HATICE). Through trial registries, we identified another five (US‐POINTER, MIND‐CHINA, MYB‐Trial, J‐Mint and AgeWell.de) that were ongoing at time of the search. Among 5381 Rotterdam Study participants (mean age 72 years, 58% women), eligibility across published trials ranged from 48% for MAPT to 87% for PREDIVA, largely mimicking estimates from original trial reports. Variability in eligibility was wider for ongoing trials, and ranged from 0.9% for US‐POINTER, to 21% for Age‐Well.de up to 94% for J‐Mint. The vast majority of individuals already qualified for both lifestyle and pharmaceutical interventions (e.g. statins or antihypertensives) based on their cardiovascular risk (ACC/AHA: from 65% for DRs EXTRA to 93% for AgeWell.de, for ESC/EAS: from 60% for DR’s EXTRA to 83% for HATICE). Remaining lifetime dementia risk was higher when individuals were at lower 10‐year cardiovascular risk.

Conclusion

Multidomain dementia prevention trials target a segment of the population that already qualifies for preventive interventions based on their cardiovascular risk according to cardiology guidelines. These findings call for adapted recruitment strategies in dementia trials, to adequately capture the population at risk in whom maximum benefit can be achieved.
Heterogeneity in imaging‐based spread of tau and atrophy in atypical AD
Authors: Whitwell Jennifer L.
Published: December 2021

Background

Different clinical phenotypes of atypical AD are each associated with characteristic patterns of neurodegeneration and tau deposition on PET. However, longitudinal patterns of tau accumulation and atrophy dissociate and there is significant subject‐level heterogeneity in patterns of progression. We investigate the degree to which heterogeneity in tau progression and atrophy is related to age, apolipoprotein (APOE) genotype and clinical progression.

Method

The Neurodegenerative Research Group (NRG) recruited 138 atypical AD patients (posterior cortical atrophy [PCA] = 57, logopenic progressive aphasia [LPA] = 81), of which 57 underwent longitudinal 3T head MRI and [18F]flortaucipir PET. Region‐of‐interest and voxel‐level analyses were utilized to assess relationships between rates of both atrophy and flortaucipir accumulation with age and APOE ε4 genotype. Principle component analysis using 12 different cognitive tests was used to assess patterns of clinical decline, with the principle components correlated to neuroimaging.

Result

Fastest rates of tau accumulation were observed in the frontal lobes in PCA and LPA, while fastest rates of atrophy were observed in occipital lobe in PCA and left temporoparietal lobe in LPA. Cortical rates of tau accumulation, particularly in the frontal lobe, were faster in younger patients and in APOE ε4 non‐carriers within LPA and PCA. Spatial patterns of tau accumulation were similar in both carriers and non‐carriers. Cortical rates of atrophy, particularly in parietal regions, were faster in younger patients in PCA and LPA, and in APOE ε4 non‐carriers. Conversely, rates of medial temporal atrophy were faster in older patients and APOE ε4 carriers. Increased rates of tau accumulation across the cortex, but particularly in frontal regions, corresponded to greater severity of clinical decline across tests over time.

Conclusion

Rates of tau accumulation and atrophy are both influenced by age and APOE genotype in atypical AD, but with different regional associations observed for each modality. These findings highlight heterogeneity present in neuroimaging signatures of atypical AD beyond clinical phenotype.
Intellectual curiosity and action initiation are subtypes of apathy affected in Huntington’s disease gene expansion carriers
Authors: Hendel Rebecca Kjærgaard , Hellem Marie Nathalie Nickelsen , Hjermind Lena Elisabeth , Nielsen Jørgen Erik , Vogel Asmus
Published: December 2021

Background

Apathy is a prevalent behavioral symptom in neurodegenerative diseases. In Huntington’s Disease, apathy can result in severe loss of function for the patient and substantial caregiver distress. The research‐based evidence of apathy is characterized by a lack of generalizability due to methodological differences. In this study we wished to characterize apathy in premanifest and motor‐manifest Huntington’s Disease gene expansion carriers and controls.

Method

82 Huntington’s Disease gene expansion carriers (premanifest and motor‐manifest) and 32 controls were included in the study (Mini‐Mental State Examination score ≥ 24 and Montreal Cognitive Assessment score ≥ 19). Apathy was quantified using the Lille Apathy Rating Scale and the Short Problem Behaviors Assessment for Huntington’s Disease. Analyses of association were performed between apathy on the Lille Apathy Rating Scale and motor function, cytosine‐adenine‐guanine repeat length, cytosine‐adenine‐guanine age product score, neuropsychiatric and cognitive screening tests.

Result

Compared to premanifest and control participants, the motor‐manifest Huntington’s Disease gene expansion carriers scored significantly higher on the global score on the Lille Apathy Rating Scale and on two subscales (Intellectual Curiosity and Action Initiation – see table 1). Likewise, motor‐manifest HD gene expansion carriers scored significantly higher on the Short Problem Behaviors Assessment for Huntington’s Disease. Significant correlations were found between apathy on the Lille Apathy Rating Scale and the motor score, the neuropsychiatric measures and the cognitive screening tests. Apathy was present in 22 % of the Huntington’s Disease gene expansion carriers (including four premanifest participants) when examined with the Lille Apathy Rating Scale. The apathetic participants had significantly higher motor score and were significantly affected on the neuropsychiatric measures and the cognitive screening tests. When entered a multiple stepwise regression model, apathy was predicted by the motor score and the depression score. No other variables could significantly predict apathy on the Lille Apathy Rating Scale.

Conclusion

Apathy is a frequent and early symptom of disease in Huntington’s Disease gene expansion carriers, and it has a specific expression that might be related to the underlying neuropathology. Apathy is related to disease progression, cognitive decline and neuropsychiatric symptoms.
Perspective taking and its structural correlates in early Alzheimer's disease
Authors: Parizkova Martina , Kalinova Jana , Nedelska Zuzana , Vyhnalek Martin , Hort Jakub , Laczó Jan
Published: December 2021

Background

There is an increasing effort to find simple and reliable tests for the early diagnosis of Alzheimer´s disease (AD). Spatial orientation deficits are present early in AD and could thus serve as an early cognitive marker of the disease. We aimed to evaluate the potential of perspective taking tests to identify individuals with early AD and to determine associations between perspective taking and volumes of the selected brain regions affected in early AD.

Method

66 participants with amnestic mild cognitive impairment (aMCI) and positive AD‐biomarkers (aMCI due to AD, n=22), aMCI and negative biomarkers (aMCI AD‐negative, n=15), mild AD dementia (n=7) and cognitively normal (CN) older adults (n=22) underwent clinical and neuropsychological evaluation, MRI brain scan with automated volumetry, AD‐biomarker assessment and two perspective taking tasks: Standardized Road‐Map test of Direction Sense (RMTDS) and Perspective Taking/Spatial Orientation Test (PTSOT). In the RMTDS, the participants followed a pathway on a city map indicating a direction of turning at each intersection. The PTSOT included pictures of arrays of objects and participants indicated direction between selected objects.

Result

The aMCI due to AD and mild AD dementia groups had lower scores than the CN group (p<0.05) in the PTSOT. The aMCI due to AD group had a lower score compared to the CN group (p<0.05) in the RMTDS. There were no differences between the CN and aMCI AD‐negative groups in both tests. PTSOT scores correlated with volumes of the right inferior temporal gyrus and right and left precuneus.

Conclusion

The perspective taking tests reliably detect spatial orientation impairment typical for early stages of AD. Worse performance in the PTSOT was associated with smaller volumes of the brain regions affected early in AD.
Brief digital cognitive assessment for detection of cognitive impairment in low‐ and middle‐income countries
Authors: Rodriguez‐Salgado Ana M , Llibre‐Guerra Jorge J , Peñalver Ana Ibis , Tsoy Elena , Bringas Giosmany , Guerra Juan C Llibre , Erlhoff Sabrina J , Allen Isabel Elaine , Valcour Victor , Kramer Joel H , Miller Bruce L , Possin Kate L , Llibre‐Rodriguez Juan J
Published: December 2021

Background

Rapid technological advances offer a possibility to develop cost‐effective digital cognitive assessment tools. However, it is unclear whether these measures are suitable for application in populations from Low and Middle‐Income Countries (LMIC).

Methods

In this cross‐sectional study, we examined the accuracy and validity of the Brian Health Assessment (BHA) in detecting cognitive impairment in a Cuban population; 146 participants (cognitively healthy=53, MCI=46, dementia=47) were recruited at primary care and tertiary clinics. The main outcomes included: accuracy of the BHA in discriminating between controls and cognitively impaired groups (MCI and dementia) and correlations between the BHA subtests of memory, executive functions, and visuospatial skills and criterion‐standard paper‐and‐pencil tests in the same domains.

Results

The BHA had an AUC of .95 (95% CI: .91‐ .98) in discriminating between controls and cognitively impaired groups (MCI and dementia, combined) with .91 sensitivity at .85 specificity. In discriminating between control and MCI groups only, the BHA tests had an AUC of .94 (95% CI: .90‐ .99) with .71 sensitivity at .85 specificity. Performance was superior to the MoCA across all diagnostic groups. Concurrent and discriminant validity analyses showed moderate to strong correlations between the BHA tests and standard paper‐and‐pencil measures in the same domain and weak correlations with standard measures in unrelated domains.

Conclusions

The BHA has excellent performance characteristics in detecting cognitive impairment including dementia and MCI in a Hispanic population in Cuba and outperformed the MoCA. These results support potential application of digital cognitive assessment for older adults in LMIC.
Neural correlates of agitation mediate the relationship between severity of depressive symptoms and memory function in healthy older adults
Authors: Park Hajeong , Park Hyeyoung , Chey Jeanyung
Published: December 2021

Background

Depressive symptoms in older adults are known to be associated with memory dysfunction. Among those symptoms, agitation is a key symptom that differentiates late life depression from general depression and is suggested as a risk factor for developing dementia. However, little is known about the relationship between depressive symptoms, including agitation, and memory function in non‐clinical elderly populations. This study aimed to find the underlying mechanism of the relationship between the severity of depressive symptoms and memory by analyzing the neural correlates of agitation.

Method

One hundred sixty‐eight healthy older adults (mean age = 72.98, SD = 6.57) were administered the Elderly Memory disorder Scale (EMS), Geriatric Depression Scale (GDS), and resting‐state fMRI. A sub‐score of the GDS reflecting agitation was used, which was constructed by network analysis of the GDS in a previous study. Functional connectivity (FC) matrices were constructed for each individual, and connections showing the effect of agitation were extracted in group‐level analysis with the effects of age, gender, and years of education controlled . These connections were confirmed to truly reflect agitation by a leave‐one‐out cross‐validation method. FC values were then used as mediators to investigate the relationships between the total GDS score and memory indices from the EMS.

Results

Functional connectivities between the ROIs of the sensorimotor network, among others associated with agitation including the frontal cortices (supplementary motor area, inferior frontal gyrus, prefrontal cortex, pre/postcentral gyrus, paracingulate gyrus, operculum) and parts of the cerebellum (anterior cerebellum, vermis), were found to mediate the relationship between the total GDS score and the long‐term memory recall index. Therefore, people with stronger FC in these regions demonstrated worse recall performance as GDS score increased

Conclusion

These results suggest that somatosensory hypersensitivity, due to excessive activation of the sensorimotor network associated with agitation, is the neural mechanism which explains how late life depression can lead to memory dysfunction.
Norms for Hispanic older adults on the National Alzheimer’s Coordinating Center’s Uniform Data Set 3.0 Neuropsychological Battery
Authors: Rosado‐Bruno Mónica , Reyes Marcos , Kiselica Andrew M
Published: December 2021

Background

Limited availability of norms for cognitive tests among older adult Hispanic individuals leads to problems with diagnosis, prognosis, and intervention. Moreover, few studies have evaluated the impact of language of test administration (i.e., Spanish vs. English) on test performance in this group.

Method

Multivariate regressions were used to evaluate the impact of demographic factors on neuropsychological test performance in a sample of cognitively normal individuals tested with the Uniform Data Set 3.0 (n = 445). Demographically adjusted norms were created for both the overall Hispanic sample, as well as for regional cultural groups, using a regression‐based approach. Formulas were incorporated into a user‐friendly calculator for easy use in clinical settings and future research.

Result

Age demonstrated a negative relationship with all cognitive scores, inversely to education. Female sex and English testing language were significantly associated with better performance on multiple tests. However, the contrary effect was found with respect to the Multilingual Naming Test. Generally consistent results were reported in assessed regional cultural subgroups.

Conclusion

Results provide much needed methods to assist with interpreting cognitive test data among older Hispanic adults. Language of test administration emerged as a critical factor for score interpretation, with scores favoring English speakers.
Nevada exploratory Alzheimer’s disease research center: Advancing dementia care in rural communities
Authors: Sabbagh Marwan Noel , Ritter Aaron , Cummings Jeffrey L. , Wint Dylan , Decourt Boris , Wong Christina G , Caldwell Jessica ZK , Kinney Jefferson W , Carriere Lucille , Cordes Dietmar , Fulkerson Nadia , Almoraissi Abla , Mandarino LeeAnn , Hartley Katurah , Shan Guogen , Miller Justin B , John Samantha E , Lombardo Joseph
Published: December 2021

Background

People with MCI and AD living in rural areas represent an understudied and underserved population in the broader AD landscape. Very little works have been done on rural cohorts by NIA‐designated Alzheimer’s Disease Research Centers (ADRCs) in the past. The Nevada Exploratory ADRC (NVeADRC) is specifically set to study AD and related dementias in rural individuals, and to systematically generate novel data on the clinical features of AD, clinical outcomes, and social determinants of health.

Method

The leading scientific objectives of the NVeADRC are to: 1) understand the occurrence of AD and optimize treatment in underserved rural settings; 2) examine risk factors associated with the development of AD in rural areas; and 3) evaluate the trajectories and progression of AD in rural versus urban communities. The NVeADRC will deploy a top‐down strategy to: 1) establish a network of stakeholders and medical partners to increase awareness of dementia in rural communities and enroll rural participants in our research cohort; 2) develop a research enterprise for longitudinal studies on dementia in rural populations; 3) progressively implement a research infrastructure rooted in technology to facilitate standardized clinical data collection from patients in rural areas.

Result

The data collected will be part of the National Alzheimer’s Coordinating Center (NACC) and shared with the larger scientific community to ultimately to improve healthcare for patients in rural areas. Target recruitment for the NVeADRC include 20 Mild Cognitive Impairment, 40 dementia due to Alzheimer’s disease and 40 cognitively normal subjects. In addition to the Uniform Data Set 3.0, we intend to collect volumetric MRI, biofluids (blood, saliva, and cerebrospinal fluid), as well as, a series of both static and dynamic social determinants of health on study subjects and their partners. All participants will be followed to voluntary withdrawal or autopsy.

Conclusion

The NVeADRC represents a unique, high impact entity within the ADRC network, and will generate high‐quality biomedical data that advance AD/ADRD research on individuals living in underserved rural communities. As we grow our project, we intend to share biospecimens and data with the scientific community.
Affective and cognitive deficits in a novel AD mouse model: A role for noradrenaline and inflammation
Authors: Sedgwick Katie Sarah , Dwyer Dominic , Good Mark A , Saito Takashi
Published: December 2021

Background

Depression has been robustly linked to Alzheimer’s disease (AD) often occurring before the onset of cognitive decline. The affective symptoms that accompany this decline are also frequently overlooked but could offer insights into the early stages of the disease and how it progresses. To examine this link in detail, animal models are good at offering a controlled and detailed assessment which could uncover whether affective insults are merely a symptom or play a significant role in disease onset. Furthermore, gender is rarely considered despite being an important risk factor for AD so understanding sex differences in disease progression will further aid this mechanistic research. For these reasons, assessing the affective and cognitive deficits of an AD mouse model will be compared to neurological insults of relevant brain areas (i.e. Locus Coeruleus (LC)) and inflammation.

Method

Using a novel Knock‐in mouse model, the AppNL‐G‐F
, behavioural analysis was used to examine affective deficits in a young cohort (n=96) aged 5‐7 months using Open field, Object in Place, Social preference test, elevated plus maze and Lick Cluster analysis. Immunohistochemistry stain for Tyrosine Hydroxylase will show any insults to the LC while a plaque and microglia stain will spatially show the inflammatory response around amyloid aggregation.

Result

At this early time point, no affective deficits were found aside from a reduction in distance moved by the AppNL‐G‐F
in the open field which could be indicative of a depressive‐like symptom but, in the absence of other deficits, will be taken at face value. There were no significant gender differences in any of the tests and this absence of behavioural effects are examined in relation to degree of neurological insult.

Conclusion

As expected, the young cohort’s lack of behavioural deficits mean they offer a good baseline before AD insult to contrast with an older (12‐14 months) cohort. This comparison is in progress assess affective symptom progression in relation to LC damage, inflammation and amyloid pathology.
Leveraging virtual reality to train certified nursing assistants as essential dementia‐care personnel in the age of COVID‐19
Authors: Balas Johanna S. , Phelps Emily Broman , Shaw Carrie , Washington Erin , Glover Crystal M , Ludwig Ghausia A , Bennett David A. , Fleischman Debra A , Volgman Annabelle Santos , Aggarwal Neelum T.
Published: December 2021

Background

COVID‐19 has placed an extraordinary and disproportionate level of responsibility and risk on certified nursing assistants (CNAs) caring for persons with dementia (PWD) relative to their training, resources, and compensation levels. Nearly one‐quarter of COVID‐19 deaths in the United States have been nursing home residents and staff. Despite providing the majority of direct care, CNAs are amongst the most under‐resourced and under‐trained frontline workers. Given their essentiality, it is critical to support CNAs during the COVID‐19 pandemic. The purpose of this work is to provide CNAs with a space to strengthen their knowledge and confidence in caring for PWD. This pilot study applies a virtual reality (VR) curriculum to train CNAs regarding the lived experiences of PWD and their loved ones. The VR vignette portrays a Latinx woman, Beatriz, through progressive stages of Alzheimer’s disease.

Method

Chicago Methodist Senior Services (CMSS) CNAs were recruited (N=7; 86% female, 86% Black) for a seven‐week online training program consisting of 1.5 hours per week. Each class included a didactic lecture and an Embodied Labs VR module depicting a first‐person experience of dementia through a distributive model approach. The program concluded with two recorded focus groups. Participants completed the UCLA Geriatric Attitudes Scale, a dementia knowledge assessment, the Interpersonal Reactivity Index surveys, and a COVID‐19 Impact questionnaire. Current analyses include qualitative content analysis for focus group data and descriptive, quantitative statistics for pre‐and post‐VR intervention surveys.

Result

Preliminary results demonstrate that CNAs endorsed a positive change in attitudes toward older adults (p=0.069), a deepened understanding of dementia, and increased confidence in caregiving skills. Focus groups allowed CNAs to discuss changes in resident behavior and support one another through a virtual platform during a global pandemic.

Conclusion

Combining traditional didactic lectures with VR‐based curricula provided CNAs with foundational knowledge and first‐hand experience of dementia pathology. Participants reported greater levels of insight and empathy for PWD. Future aims include expansion of training content to include end‐of‐life conversations, LGBTQIA aging, and Lewy body dementia.
Education and brain amyloid load act on temporal lobe function in individual with subjective memory complaint: An EEG‐fMRI study
Authors: Lizio Roberta , Lopez Susanna , Hampel Harald , Chiesa Patrizia Andrea , Del Percio Claudio , Noce Giuseppe , Teipel Stefan J. , González‐Escamilla Gabriel , Bakardjian Hovagim , Cavedo Enrica , Lista Simone , Vergallo Andrea , Lemercier Pablo , Spinelli Giuseppe , Grothe Michel J. , Potier Marie‐Claude , Stocchi Fabrizio , Ferri Raffaele , Habert Marie‐Odile , Dubois Bruno , Babiloni Claudio ,   INSIGHT‐preAD Study Group
Published: December 2021

Background

The cognitive reserve (CR) moderate the effect of brain pathophysiology on cognitive deficits in Alzheimer's Disease (AD) continuum. In a previous study on individuals with subjective memory complaint (SMCs), a condition at risk for AD, from the INSIGHT‐preAD cohort, we found that CR altered the association of amyloid load with neurophysiological mechanisms generating posterior electroencephalographic (EEG) alpha rhythms in quiet wakefulness. We used educational attainment (Edu) as an indicator of CR.

Method

In the present work we tested the hypothesis of the interaction of Edu and cerebral amyloid‐b load with the association between posterior alpha rhythms, as revealed by resting‐state EEG (rsEEG) activity, and functional connectivity, as revealed by functional magnetic resonance imaging (fMRI, 3‐Tesla Verio system), among cholinergic basal forebrain (BF), thalamus, and posterior cortical areas. Resting‐state EEG and fMRI data were acquired in 318 cognitively intact individuals (age between 70 and 85 years) with SMC. Participants were stratified into two groups of amyloid‐positive (SMCpos) and ‐negative (SMCneg), using the standard diagnostic markers of Alzheimer's neuropathology based on cortical‐to‐cerebellum standardized uptake value ratio in the PET imaging. Then, the education attainment level was used to stratify the SMC participants in those with a low‐to‐moderate education level (SMC Edu‐) and those with a high education level (SMC Edu+).

Result

Results showed a significant positive association between temporal alpha rhythms and above‐mentioned functional connectivity in the SMC cases with low brain amyloid accumulation and education attainment (SMCneg Edu‐). In contrast, the SMCneg Edu+ seniors showed the amplest posterior alpha rhythms, but not a positive association between temporal alpha rhythms and fMRI connectivity among cholinergic BF, thalamus, and posterior cerebral cortex, possibly due to a (annulation) of high CR. Of note, the SMCpos Edu+ seniors showed this positive association, possibly due to the (neutralization) of CR and brain amyloidosis (Figure 1).

Conclusion

The present results suggest that, in SMC seniors, high CR affects cortical neural synchronization mechanisms generating posterior rsEEG alpha rhythms, but not through the ascending cholinergic system to the posterior cortex. Unfortunately, these CR effects may be annulled at earlier stages of Alzheimer's amyloid pathophysiology.
Comparison neuropsychological test between early‐onset and late‐onset Alzheimer’s disease patients
Authors: Tong Trang Mai
Published: December 2021

Background

Early‐ onset Alzheimers disease (EOAD) has been overshadowed by the more common late‐ onset AD (LOAD) due to differ diverse clinical features and frequency of nonamnestic presentation.

Method

Case‐series. Cases selected among the patient diagnosed Alzheimer disease (probable‐ DSM 5) with MMSE scores ≥ 15.

Result

21 EOAD and 27 LOAD were analyzed neuropsychological test: MMSE, clock‐drawing test, modified Boston naming, verb fluency, trail‐making A, immediate recall, delayed recall, delayed recognition, digit span forward, digit span backward. EOAD group have worse result at modified Boston naming test and clock‐drawing test (p <0.05), represented language and visual impairment than LOAD.

Conclusion

EOAD have differ neuropsychological test from LOAD.
Higher intraindividual variability in neuropsychological test performance is associated with reduced cerebral blood flow in older adults
Authors: Holmqvist Sophia L. , Thomas Kelsey R. , Edmonds Emily C. , Calcetas Amanda T. , Edwards Lauren , Bangen Katherine J.
Published: December 2021

Background

Intraindividual variability (IIV) across neuropsychological measures within a single testing session has become a promising sensitive marker predictive of cognitive decline and development of Alzheimer’s disease (AD). We have previously shown that higher IIV is associated with medial temporal lobe atrophy. However, to our knowledge, IIV has yet to be examined in relation to cerebral blood flow (CBF). Therefore, we examined associations between IIV and regional CBF among older adults free of dementia.

Method

141 Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants underwent neuropsychological testing, magnetic resonance imaging (MRI), and florbetapir positron emission tomography (PET) imaging. The IIV index was calculated as the intraindividual standard deviation across 6 demographically‐corrected neuropsychological measures. Mean neuropsychological performance was computed as the mean of the 6 z‐scores. Pulsed arterial spin labeling MRI was used to quantify CBF. Six free‐surfer derived a priori CBF regions of interest were examined: entorhinal cortex, hippocampus, inferior temporal cortex, inferior parietal cortex, rostral middle frontal gyrus, and medial orbitofrontal cortex. PET amyloid‐β (Aβ) positivity was determined using the recommended threshold for cross‐sectional florbetapir of 1.11 using whole cerebellum as the reference region.

Result

In the entire sample, linear regression models showed that after adjusting for age, sex, mean neuropsychological performance, and regional cortical thickness, greater IIV was significantly associated with lower inferior parietal CBF (β=‐2.712, p=.004), inferior temporal CBF (β=‐3.259, p=.001), and reduced entorhinal CBF at trend level (β=‐.407, p=.073). Sensitivity analyses showed that among Aβ+ individuals, greater IIV was significantly associated with lower CBF in inferior parietal (β=‐2.729, p=.018) and inferior temporal regions (β=‐2.704, p=.043). In Aβ‐ individuals, there were no significant associations between IIV and CBF (all ps>.05).

Conclusion

IIV may be sensitive to early cerebrovascular changes in AD‐vulnerable regions above and beyond demographics, mean neuropsychological performance, and cortical thickness. These relationships were seen among Aβ+ individuals, suggesting that IIV may be a marker of early brain changes among those individuals on the AD continuum. Future studies should examine how IIV may predict future brain and cognitive changes in more diverse samples and among those with greater vascular risk burden.