bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of brain networks activity and their association with transfer of cognitive training gains
Authors: Faraza Sofia , Hergert Lena , Dyrba Martin , Wolf Dominik , Fischer Florian U , Knaepen Kristel , Kollmann Bianca , Tüscher Oliver , Binder Harald , Mierau Andreas , Riedel David , Fellgiebel Andreas , Teipel Stefan
Published: December 2022

Background

Age‐related cognitive decline increase the need for cognitive interventions to maintain cognitive function. Transfer of training gains to untrained tasks is a key indicator for the effectiveness of cognitive training. However, the underlying brain mechanisms need to be further investigated. We implemented a cognitive training study to assess functional connectivity determinants of transfer of training gains.

Method

A sample of 181 healthy older adults (mean age: 68 years) underwent a 4‐week cognitive training across three sites. The control group consisted of 54 older adults. To evaluate transfer and training effects, participants underwent a neuropsychological assessment before and after the training. A second follow‐up assessment was applied 12 weeks after the training. The training group was divided in subjects who had and who did not have successful transfer, which was defined as higher improvement in cognitive tasks than the control group. We used cognitive scores representing working memory, verbal and visuospatial memory and executive functions. Baseline resting‐state functional magnetic resonance imaging was assessed in order to investigate the functional connectivity of brain networks associated with cognitive functions.

Result

Cognitive performance of the training group remained stable across time and did not show a significant improvement. Transfer of training gains directly after the training was limited. However, our participants were able to maintain gains 12 weeks after the training. We hypothesized a higher functional connectivity of brain networks, such as Default Mode Network or the Executive Network, to be associated with successful transfer of cognitive gains. Investigation of brain networks activity and the association with transfer of training gains is currently ongoing and complete results will be presented at the conference.

Conclusion

Transfer of training gains in aging is possible, but it remains limited. Cognitively healthy older adults might not have major benefits from a 4‐week cognitive training. Our results could help to identify healthy older adults who will most benefit from training and understand the brain mechanisms underlying transfer of cognitive gains.
M1 muscarinic acetylcholine receptor positive allosteric modulators do not disrupt sleep in aged cynomolgus macaques
Authors: Gould Robert W , Lekander Alex D , Curry C Ryan , Lavalley Nina , Russell Jason K , Newhouse Paul A , Nader Michael A , Jones Carrie K
Published: December 2022

Background

Age‐related changes in sleep may directly contribute to cognitive dysfunction and underlying pathological progression contributing to Alzheimer’s Disease or related dementias (AD/ADRDs). While acetylcholinesterase inhibitors (AChEIs) are FDA‐approved for the treatment of AD‐related cognitive impairments, these drugs also disrupt sleep. Positive allosteric modulators (PAMs) targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) have produced cognitive and arousal enhancing as well as sleep‐modifying effects in aged and/or AD rodents models. The present study provided the first comparison of baseline sleep measures in young and old monkeys, then examined the effects of novel M1 mAChR PAMs VU0486846 and VU0453595, compared with the AChEI, Donepezil on sleep in aged monkeys.

Method

Eight young adult (4 male/4 female, 6‐8 years old) and 10 aged cynomolgus macaques (6 males/4 females, 19‐25 years old) were implanted with subcranial electrodes and a wireless transmitter (L04, DSI) for undisturbed telemetric recording of electroencephalography (EEG) from their home cage. After baseline sleep assessments, aged monkeys were tested once weekly with donepezil (3.0‐10 mg/kg, PO), VU0486846 (3.0‐30 mg/kg, PO), or VU0453595 (1.0‐10 mg/kg, PO), administered 2 hours prior to lights out (0600:1800 light:dark schedule). EEG was recorded and sleep stages including total sleep time (TST), % TST in rapid eye movement sleep (REM), N1, N2, and N3 non‐REM sleep were determined and summed across the 12 hour dark period.

Result

Aged monkeys showed significantly less % TST in N3 and REM sleep and increased N1 sleep compared to young monkeys. Donepezil dose‐dependently reduced TST, increased % REM and trended toward a decrease in N2 and N3 stage sleep. In contrast, M1 PAMs, within dose ranges known to be physiologically active in monkeys, did not alter sleep parameters.

Conclusion

Aged‐related and donepezil‐mediated sleep disruptions in aged monkeys are consistent with the clinical literature. Lack of effects by M1 mAChR PAMs in aged monkeys when dosed prior to lights out may suggest fewer disruptive effects compared to AChEIs or that there is insufficient cholinergic tone for an M1 PAM to alter sleep. Future studies will assess the arousal enhancing effects of M1 PAMs when dosed during waking periods in aged monkeys.

Funding: AG054622, DA017763
Lithium boosts neuronal bioenergetics in Alzheimer’s disease
Authors: Adlimoghaddam Aida , Andreazza Ana C. , Albensi Benedict C
Published: December 2022

Background

Alzheimer's disease (AD) is characterized by the accumulations of amyloid beta and neurofibrillary tangles in brain tissue; however, AD is multifactorial and different etiopathogenic mechanisms involves that can affect mitochondrial function that are associated with AD. In the current study, we investigated the effect of lithium on mitochondrial function in AD.

Method

Neuronal cells were isolated separately from hippocampal of brain tissue of control mice (C57BL/6) and 3xTg model of AD. Mitochondrial oxygen consumption rate (OCR), mitochondrial Cytochrome C Oxidase (COX) activity, and total ATP activity were measured in control vs. AD neurons after one day and seven days dose‐dependent treatment with lithium.

Result

In the present study, short and long term lithium treatment significantly increased (p<0.05) mitochondrial OCR, COX, and total ATP level in 3xTg neurons. However, lithium had no effect on energy metabolism in control neurons. Together, these data indicate that lithium improves mitochondrial function under pathological states.

Conclusion

Overall, these results have important implications for the treatment of disorders in which brain energy regulation are compromised, including AD. Particularly, our results highlight a role for lithium in regulating bioenergetics in early stage AD and suggest that neuronal cells may be a crucial therapeutic target for preventing AD.
Risk factors and cognitive domain markers of progression in Subjective Cognitive Decline
Authors: Bubu Omonigho Michael M , Mbah Alfred , Masurkar Arjun V
Published: December 2022

Background

Subjective cognitive decline (SCD) is considered a preclinical stage of Alzheimer’s disease, but drivers and nature of progression remain unclear. We evaluated risk factor differences between SCD decliners and non‐decliners related to demographics, genetics, and presence of comorbidities. We also investigated cognitive domain markers associated with progression over time.

Method

A longitudinal analysis was performed on subjects with SCD at baseline from the NYU Alzheimer’s Disease Research Center. We included subjects classified as non‐decliners (n = 27), who remained stable for six annual visits, and decliners (n = 24), who progressed to mild cognitive impairment or worse between the second to sixth follow‐up visits. Generalized linear models examined group differences in demographic and genetic (presence of APOE4 or APOE2 allele) risk factors. Linear and logistic mixed‐effects models with random intercept and slope examined associations of psychometric test performance and comorbidities with longitudinal decline, comparing decliners to non‐decliners. Models included age, sex, education, Hispanic ethnicity, baseline psychometric data, APOE status, and their interactions with time. Time was operationalized as years from baseline for each participant.

Result

Mean (SD) age was 68.5 (11.3) vs. 66.3 (7.1) years (p = 0.41), and follow‐up time was 3.7 (1.97) vs. 6.3 (1.60) years, (p <0.001) for decliners vs. non‐decliners. Subjects with lower years of education (14.9 (3.2) vs. 17.3 (2.1)) and those of Hispanic ethnicity (52.2% vs. 47.8%) were more likely to be decliners (p ≤ 0.004 for both). There were no differences in APOE2 or APOE4 status between decliners vs. non‐decliners. Decliners were approximately 7 times more likely (aOR: 6.67; 95% CI: 1.30 – 33.33, p = 0.002) to have hypercholesterolemia compared to non‐decliners. SCD decliners were at increased risk for psychometric changes in memory, executive, and language domains (p < 0.001 for all).

Conclusion

In this cohort, lower education, Hispanic ethnicity, and hypercholesterolemia are risk factors for progression in SCD, whereas APOE status is not. Although SCD has been primarily defined with regard to concern about memory, SCD decliners are at increased risk for both amnestic and non‐amnestic cognitive decline. This supports further work to relate risk factors to SCD outcomes.
Identification of Mild Cognitive Impairment Among Black and White Community Dwelling Older Adults Using NIH‐Toolbox Cognition Tablet Battery
Authors: Rigby Taylor , Gregoire Allyson , Reader Jonathan M , Kairys Anson , Bhaumik Arijit K , Rahman‐Filipiak Annalise , Hampstead Benjamin M. , Kavcic Voyko , Giordani Bruno
Published: December 2022

Background

NIH Toolbox‐Cognition Battery (NIHTB‐CB) is a computerized cognitive assessment battery frequently used in clinical research. However, the utility of the tablet adaptation has not been well established for clinical characterization, nor have possible racial differences been examined. We aim to identify which of the NIHTB‐CB subtests best differentiate healthy controls (HC) from those with mild cognitive impairment (MCI), as well as examine possible differences in diagnostic identification between Black/African‐American (B/AA) and white older adults.

Method

Participants were community‐dwelling adults 65 years and up (HC = 96; MCI = 63), recruited through affiliated studies within the Michigan Alzheimer’s Disease Research Center (NIA/NIH‐P30AG053760) and diagnosed by consensus conference through National Alzheimer’s Coordinating Center criteria. They then completed the NIHTB‐CB tablet version for iPad. Discriminant function analysis was used to determine which cognitive tests best differentiated clinical diagnoses in the total sample and separately for B/AA (n = 81) and white participants (n = 78).

Result

In the total sample, 78% of cases were correctly identified with Picture Sequence Memory (PSM; Standardized Coefficient (SC) = ‐.73) being the strongest predictor. The cross‐validated model correctly identified 79.2% of HCs and 60.3% of MCIs. Analyses were then stratified by race. In the B/AA sample, the model was able to correctly identify 60% of HCs and 68.4% of MCIs, with PSM (SC = .68) being the strongest predictor followed by List Sorting Working Memory (LSWM; SC = .42). In the white sample, 83% of HCs and 44% of MCIs were correctly identified and PSM (SC = .84) was the strongest predictor.

Conclusion

As more treatments become available for Alzheimer’s disease, it is increasingly important to identify preclinical stages, such as MCI, so that we may intervene as early as possible in the disease process. NIHTB‐CB is one tool that may aid in identification. The memory subtest PSM was the best predictor of diagnosis in each model. While the overall model was fairly accurate at predicting clinical diagnosis, the models proved less accurate when cross validated and stratified by race. Thus, our results suggest that it may be important to consider race and other aspects in identifying specific diagnostic groups.
How Can Pet Robots Be Embedded Into Nursing Homes as Part of Routine Dementia Care?
Authors: Koh Wei Qi , Casey Dympna , Toomey Elaine
Published: December 2022

Background

In the last decades, pet robots have started to gain traction as a technology‐based alternatives for animal‐assisted therapy. Several studies have been conducted to evaluate the effectiveness of pet robots for people living with dementia, particularly in residential care settings. Despite findings of their potential to deliver psychosocial benefits for nursing home residents with dementia, the knowledge translation from research to clinical practice remains slow, and the uptake of pet robots in clinical practice remains low. The purpose of this study was to identify strategies to guide the implementation of pet robots into routine dementia care in nursing homes.

Method

A preceding qualitative inquiry and a scoping review was conducted to identify determinants of implementing pet robots. To ensure that the multilevel nature of implementation was captured, the Consolidated Framework of Implementation Research (CFIR) was used to guide the conceptualisation and conduct of the both studies. Next, we identifed implementation strategies to address the identified determinants. This was done by mapping determinants to the Expert Recommendations for Implementation (ERIC), a taxonomy of 73 implementation strategies, using the CFIR‐ERIC mapping tool. Findings from the preceding studies were used to contextualised the identified strategies. Finally, we consulted with key stakeholders and a Patient and Public Involvement member to further refine the list of implementation strategies.

Result

Implementation determinants were mapped to all nine clusters of implementation strategies in the ERIC taxonomy. Most implementation strategies were focused on the development of stakeholder relationships, such as conducting local consensus discussions to identify the need or priority of having pet robots, training and educating stakeholders such as conducting educational meetings, and the use of evaluative and iterative strategies such as conducting a local needs assessments.

Conclusion

To the best of our knowledge, this is the first study to identify implementation strategies for embedding pet robots into nursing homes for routine dementia care. Findings from this study have practical utility for clinical researchers, organisations and clinicians to guide the translation of the research on pet robots into real‐world practice.
Evaluation of the performance of alternative models in analyzing longitudinal data for Alzheimer clinical trials compared to MMRM
Authors: Wang Guoqiao , Li Yan , Xiong Chengjie , Liu Lei , Kennedy Richard E , Schneider Lon S. , Natanegara Fanni , McDade Eric , Bateman Randall J.
Published: December 2022

Background

Secondary prevention clinical trials (stage 2) for Alzheimer disease (AD) typically employs a cognitive composite score, consisting of multiple cognitive test scores, as the primary endpoint because of its sensitivity to subtle cognitive change. The underlying assumptions of using a composite score are that: (i) the treatment if effective will lead to similar treatment effects in each of its component (e.g., ∼25% reduction in the placebo progression); and (ii) the estimated treatment is an average of the treatment effects across the components regardless the satisfaction of assumption (i). The composite is typically analyzed using mixed models for repeated measurements (MMRM). Under the same assumptions, we proposed to analyze the composite using the multivariate MMRM (mMMRM) and the proportional mMMRM (PmMMRM). On the other hand, CDR SB is often used as the primary endpoint in early‐stage AD trials (stage 3), however, 20% to 30% of the placebo patients demonstrated no progression during an 18‐month follow‐up. These non‐progression participants would dilute the treatment effect comparison under the MMRM analysis. Because CDR SB is an ordinal rank measure, we propose to analyze it using the Cox proportional hazards model for recurrent events, where a recurrent event is defined as any ordinal increment over the previous visit. The goal of this study is to evaluate the performance (i.e., power) of these alternative models relative to MMRM.

Method

We evaluate the performance using both simulated data and the real trial data from the EXPEDITION 1 and EXPEDITION‐2 placebo arms.

Result

Based on simulated data, for the cognitive composite, mMMRM yielded similar power to MMRM and PmMMRM led to 5‐8% power improvement over MMRM for a two‐component composite. PmMMRM’s power advantage is expected to increase with the number of components in the composite. For CDR SB, Cox model for recurrent events yielded up to 20% greater power than MMRM. Comprehensive evaluation will be reported based on real trial data.

Conclusion

Alternative models such as PmMMRM or Cox model with the same underlying assumption as or analyzing the data with a different angle from MMRM should be explored to obtain greater power.
Preliminary Analysis of Aspects of Caregiving among Spousal Caregivers and Adult Child Caregivers for Persons with Dementia
Authors: Lewis Nicole E. , Papazyan Anna , Flatt Jason D. , Kietzman Kathryn G. , Song Yeonsu
Published: December 2022

Background

While dementia caregiving experiences may vary across individuals, many studies have focused on the negative aspects of caregiving and reducing caregiver burden and stress. Understanding both positive and negative aspects of caregiving is essential, particularly between different caregiver types. This study aimed to compare positive and negative caregiving experiences between spousal and adult child caregivers. We also examined whether the caregiver type (spousal caregivers vs. adult child caregivers) is a significant factor predicting these caregiving experiences.

Method

We analyzed baseline data from an ongoing trial to manage sleep problems among persons with dementia (PwD) and their caregivers. Demographic data, Positive Aspects of Caregiving (PAC), Zarit Burden Interview (ZBI), and Center for Epidemiological Studies of Depression (CESD) data were collected from 39 caregivers (n = 27 spouses, n = 12 adult children; 82% women, 54% Whites). Descriptive and bivariate analyses and multiple regression models were conducted.

Result

Adult child caregivers reported that providing care for their loved one made them feel more appreciated than spousal caregivers (4.25±1.21 vs. 3.48±0.97, respectively); however, they felt more stress when caring for the PwD and trying to meet other family and work responsibilities (2.75±0.86 vs. 2.07±0.99, respectively) and felt they should be doing more for the PwD (2.17±0.71 vs. 1.30±1.07, respectively; all p<0.05) than did spousal caregivers. No significant differences were found in the PAC and the ZBI total scores by caregiver type. In a separate regression model, CESD total score was the only significant factor predicting PAC and ZBI total scores, controlling for caregiver type, race (Whites vs. others), level of education, employment status, and years of caregiving. However, only the model predicting the ZBI total score was statistically significant (p<0.01, adjusted R2 = 54%).

Conclusion

These preliminary findings suggest a critical need to better understand positive and negative caregiving experiences, particularly among adult child caregivers. Assessment of depressive symptoms should be included when examining caregiving experiences among spousal and adult child caregivers. Future studies are warranted to test whether characteristics of PwD or support received by caregivers would contribute to positive or negative caregiving experiences across caregiver types.
MCI performance classification improves with a brief vocabulary test
Authors: Woods David L. , Hall Kathleen , Williams Garrett , Baldo Juliana , Chok Jas M. , Lwi Sandy J. , Blank Michael , Geraci Kristi , Herron Tim , Schendel Krista , Johnson David K
Published: December 2022

Background

Scores on cognitive tests in the bottom 7% of normative distributions are consistent with the possible diagnosis of mild cognitive impairment (MCI). The identification of patients with MCI is improved by correcting for the influence of demographic factors such as Age, Education, and Gender (AEG), on performance. Here, we evaluated whether estimates of premorbid verbal IQ derived from a brief vocabulary test would further improve classification accuracy.

Method

We obtained vocabulary scores from 441 healthy adults (mean age = 65.1 ±14.4) using the 4‐min vocabulary subtest of the California Cognitive Assessment Battery (CCAB). The vocabulary subtest included 24 multiple choice items that adapted in difficulty based on the examinee responses using a 2:1 staircase with adjustable step sizes (Figure 1). Tests were telemedically administered in participants’ homes by an experienced proctor who monitored performance via a web‐based interface.

Result

Unlike cognitive measures of fluid intelligence, vocabulary scores improved significantly with Age (r = 0.25, p < 0.001, Figure 2). Scores were also higher for participants with more education and female gender. Vocabulary z‐scores were therefore calculated after correcting for the influence of Age, Education, and Gender. Vocabulary z‐scores correlated significantly with total recall scores on the Bay Area Verbal Learning Test (BAVLT, n = 398 participants, r = 0.35, p < 0.001) and significantly improved model fit when added to AEG regressors (z = 2.1, p< 0.02 one tailed)L the AEG model accounted for 25.6% of BAVLT score variance, whereas the AEG+vocabulary (AEG+V) model accounted for 34.7% of variance. AEG and AEG+V models classified different participants in the MCI performance range: 44% of participants in the lowest 7% of scores in the AEG+V model fell within the normal range in the AEG model, while 32% of participants classified as MCI in the AEG model fell within the normal range on the AEG+V model (Figure 3).

Conclusion

The current results suggest that a brief vocabulary test improves MCI classification accuracy among older participants.
FTD Disorders Registry (FTDDR) Research Readiness Survey: Assessing awareness and attitudes towards participation in research
Authors: Reddy Sweatha , Harlass Sherry , Vincent Lakecia , Wheaton Dianna K.H.
Published: December 2022

Background

FTDDR is a web‐based, contact and research registry to amplify the patient/family voice and facilitate research for frontotemporal degeneration (FTD), a rare group of early‐onset dementia disorders. FTD not only alters cognition but also impacts behavior, personality, language, and movement. No treatments or cures are currently available, underscoring the need for research participation.

Method

The Research Readiness Survey was designed to assess knowledge of basic research principals and index perceptions of the value of research studies and clinical trials among the lay community. The 23‐question survey was administered online to FTDDR participants between March 2017 and January 2022 using a multiple‐choice and True/False‐style format.

Result

Respondents (n = 750) were 80% caregivers/biological family members and 20% FTD diagnosed persons responding independently or with care partner/helper assistance (31% male, 69% female; age range = 50‐74 years). FTD diagnoses represented among the respondents were behavioral variant FTD (bvFTD 55%), primary progressive aphasia (PPA 17%) progressive supranuclear palsy (PSP 9%), corticobasal degeneration/syndrome (CBD/CBS 7%), FTD with motor neuron disease (FTD‐ALS 4%), and other/diagnosis pending (8%). Research studies were viewed positively by the majority of respondents (85%) and this was similarly reflected by a high willingness to participate (84%) in a research study/clinical trial, especially if it was about treating or preventing disease. 64% of respondents ranked their understanding of clinical trial concepts as knowledgeable‐to‐very knowledgeable which was subsequently supported by 87% correctly answering 8 of 10 questions about principals of research. Barriers to participation in research included fear that the study would be too difficult physically/emotionally (28%), concern about time off from work (25%) and lack of reimbursement for travel expenses (20%). Most respondents (68%) reported that additional information and education about research studies/clinical trials would increase their ability to evaluate participation.

Conclusion

Survey results indicated that while FTDDR members have a positive perception of research and are relatively knowledgeable about principals of participation, there is a strong desire for additional information and education to empower informed decision‐making. Understanding and addressing perceived barriers as well as creating person‐centric studies with emphasis on participant‐facing educational materials may increase research study participation.
Exploring effect of known Alzheimer disease genetic loci in the Peruvian population
Authors: Cornejo‐Olivas Mario , Rajabli Farid , Kushch Nicholas A. , Mena Pedro Ramon , Illanes‐Manrique Maryenela , Adams Larry D. , Whitehead Patrice L. , Hamilton‐Nelson Kara L. , Milla‐Neyra Karina , Marca Victoria , Sarapura‐Castro Elison , Manrique‐Enciso Carla , Mejía Koni K. , Isasi Rosario , Castro‐Suarez Sheila , Araujo‐Aliaga Ismael , Custodio Nilton , Montesinos Rosa , Griswold Anthony J. , Dalgard Clifton L. , Beecham Gary W. , Cuccaro Michael L. , Vance Jeffery M. , Pericak‐Vance Margaret A.
Published: December 2022

Background

Native American populations are substantially underrepresented in Alzheimer disease (AD) genetic studies. The Peruvian (PE) population with up to ∼80 of Amerindian ancestry (AI) provides a unique opportunity to assess the role of AI ancestry in AD. We performed whole‐genome sequencing in PE case‐control study to assess the effect of the known AD loci in PE population.

Methods

Whole‐genome sequencing was performed in 96 AD cases and 145 unrelated cognitive healthy controls from PE population. We calculated the global ancestry (principal components) using the EIGENSTRAT approach. We tested 21 AD lead variants from the recent large non‐Hispanic White (NHW) GWAS of AD (Kunkle et al. 2019). We performed association analyses using logistic regression model with accounting for age, gender, and population substructure (first three principal components). We used Bonferroni approach for multiple test correction.

Results

Logistic regression analysis confirmed association of APOE with AD (rs429358, OR=3.6, CI:1.9‐7.0; pv < 8.4e‐05) in PE population. CLU loci (rs9331896, pv=9.3e‐04) passed the significance threshold after Bonferroni multiple test correction. Two AD loci demonstrated nominal associations (pv<0.05), which were EPHA1 (rs10808026, pv = 0.028), and FERMT1 (rs17125924, pv=0.022) loci.

Conclusion

Our results showed that known AD APOE and CLU loci are significantly associated with AD in PE population. Some of the genes demonstrated suggestive associations, but further analysis with a larger sample size is on‐going to determine if these reflect true associations.
Feasibility of community‐based remote, biometric data collection in persons with Alzheimer’s disease and behavioral symptoms
Authors: Rhodus Elizabeth K. , Kryscio Richard J , Barber Justin M , Burhan Amer M. , Jicha Gregory A
Published: December 2022

Background

Aging at home with Alzheimer’s disease (AD) is progressively difficult due to cognitive dysfunction interfering with persons’ functional activity and behavioral regulation. Community‐based collection of biometric data via wearable devices provide an innovative approach as a measure of behavioral symptomology. This study analyzes feasibility of remote, biometric data collection during a non‐pharmacological, home‐based randomized controlled trial of older adults with AD.

Methods

Individuals, aged 65 or older, with diagnosis of AD as primary dementia type and behavioral symptoms who resided in the community were included in this prospective study. ActiGraphs were mailed to care partners who implemented device use and management. Feasibility was assessed via accepting and wearing of the device by the person with AD through care partner facilitation at baseline and post‐intervention (continuous wear for 6 days at both time points). Baseline actigraphy data (mean motor activity; MMA) were assessed to determine utility of acceptance/wearing the device as means to collect biometric data. Secondary analyses assessed Pearson correlation of demographic information including cognition measured by the Montreal Cognitive Assessment and the Neuropsychiatric Inventory‐Questionnaire (NPI‐Q).

Results

Twenty‐one participants with AD engaged in the study. Eighteen participants completed baseline data collection (three caregivers refused the device on behalf of person with AD). Fourteen participants or 66.7% (95% CI: 46.6% to 86.8%) also completed post‐intervention data collection (one dropout in mid‐study and three care partners refused the device at second time point). Baseline MMA data were measured: 24‐hour MMA = 608,913; daytime MMA = 253,534; evening MMA = 308,113; nighttime MMA = 47,079. Age (x̄ = 77.8±1.7; r = ‐.56, p‐value = 0.038) was negatively correlated and cognitive impairment (x̄ = 11.13±2.3; r = .789, p‐value = 0.002) was positively correlated with 24‐hour MMA. NPI‐Q total and emotional items (agitation, anxiety, liability) were not correlated in this sample.

Conclusion

Community‐based biometric data collection for older adults with AD and behavioral symptoms is feasible. Behavioral disturbance and care burden likely lowered acceptability of the device. Future power calculations anticipating 66% compliance maybe sufficient for primary outcome analyses in community‐based data collection. Additional studies are needed to validate wearable devices as a primary outcome measure for behavioral symptoms in community‐based participants as this study was not sufficiently powered for such analyses.
Admixed ancestral composition with Amerindian predominance at the Peruvian Alzheimer Disease Initiative (PeADI)
Authors: Cubas‐Montecino Diana , Rajabli Farid , Illanes‐Manrique Maryenela , Kushch Nicholas A. , Mena Pedro Ramon , Whitehead Patrice L. , Hamilton‐Nelson Kara L. , Milla‐Neyra Karina , Marca Victoria , Sarapura‐Castro Elison , Manrique‐Enciso Carla , Mejía Koni K. , Isasi Rosario , Castro‐Suarez Sheila , Araujo‐Aliaga Ismael , Custodio Nilton , Montesinos Rosa , Griswold Anthony J. , Dalgard Clifton L. , Beecham Gary W. , Cuccaro Michael L. , Vance Jeffery M. , Cornejo‐Olivas Mario , Pericak‐Vance Margaret A.
Published: December 2022

Background

Current genetic studies for AD and other dementias are making efforts to incorporate underrepresented populations including admixed Latinos. Peruvian population is characterized by admixed ancestry with a significant Amerindian component, which varies according to specific regions across Peru. The Peruvian Alzheimer Disease initiative (PeADI) was developed to ascertain a cohort for AD and other related dementias for genetic studies in Peru. We aim to determine the patterns of continental ancestry by regions across Peru.

Methods

Over the last 3 years, The PeADI study has recruited 212 unrelated cognitive participants through collaborative health centers and community outreach ascertainment strategies. Cases were assessed by neurologists following NINDS‐ADRDA criteria. Controls were screened using MMSE, Clock drawing test and Pfeffer functional activities questionnaire. Genome‐wide genotyping was performed by Illumina screening array. PC‐AiR and model‐based. The cohort was divided into five regions (Northern, Southern, Lima, Central Highlands, and Amazonian) based on place of birth of the participant or the ancient known ancestor.

Results

The global Admixture analysis showed that Peruvians have a substantial Amerindian component (63.6%), followed by European (35.9%), African (2.5%) and East Asian (2.1%) components. When analyzed by regions, we found that the Central region concentrates the highest Amerindian ancestry (72.7%), followed by the Northern region (58.2%), Lima and Callao (57%), the Amazonian region (55.6%), and the Southern region (55.1%). The highest European ancestry is located in the Amazonian region (42.1%), while the Central region has the lowest (26.6%). African and East Asian ancestry has little influence in Peru, being the Northern with the higher African component (4.1%), and Lima and Callao the region with the higher East Asian component (3.5%). There is no significant for Amerindian component across five regions (p=0.054); however, Central highlands region has higher Amerindian component compared to Lima (p=0.005), the Northern (p=0.005) and Southern(p=0.017) regions.

Conclusion

Our results confirmed the ancestry admixture of the Peruvian population with predominance of the Amerindian component. The Central region concentrates the highest Amerindian ancestry compared with other regions across Peru.
A Multi‐domain Lifestyle Intervention does not Improve Health and Cognitive Outcomes Among APOE e4 Carriers after 4‐months
Authors: Gills Joshua L. , Jones Megan , Campitelli Anthony , Paulson Sally , Madero Erica N. , Myers Jennifer Rae , Bryk Kelsey Nicole , Glenn Jordan M. , Gray Michelle
Published: December 2022

Background

Alzheimer’s Disease (AD) currently affects 24 million individuals worldwide, this rate is expected to triple by 2050. The greatest genetic risk for AD is apolipoprotein E (ApoE; e4 allele carriers), e4 carriers typically exhibit abnormal regulation of lipoprotein metabolism. It is important to understand whether multi‐domain lifestyle interventions can mitigate cognitive decline and improve overall health in ApoEe4 carriers. Thus far, the data are mixed due to sample sizes and methodological limitations. Therefore, the purpose of this present investigation is to determine if a digital multi‐domain intervention (MDI) can improve health and cognitive outcomes in cognitively at‐risk e4 carriers over 4 months.

Method

Adults 45‐75 years old participated in this present investigation, each participant was randomly assigned to a health coaching intervention group (HC; n=61 non‐carriers; n=24 e4 carriers) or health education control group (HE; n=62 non‐carriers; n=20 e4 carriers). Participants completed weight, height, venous blood draw, a digital memory and associative learning test during baseline and 4‐month follow‐up visits. A 2 (time) x 2 (group) x 2 (APOE) factorial‐ANOVA was utilized to examine differences in the dependent variables (body mass index (BMI), cholesterol, triglycerides, memory, learning). Age, sex, and education were accounted for.

Result

Triglycerides significantly increased among HC e4carriers compared to HC non‐carriers (p=.009). BMI significantly increased among carriers regardless of intervention group compared to non‐carriers (p< .001). Cholesterol values showed a decreasing trend among HC non‐carriers, HE carriers, and non‐carriers compared to no change among HC carriers (p=.118). At both time points, e4 carriers in HE and HC exhibited significantly lower scores on memory tasks compared to non‐carriers (p=.020). HC non‐carriers saw a significant increase in associative learning scores, HC e4carriers and HE group (e4 carriers and non‐carriers) showed decreases in an associative learning task (p=.016).

Conclusion

HC e4 carriers are unresponsive to a MDI lifestyle intervention compared to non‐carriers after 4‐months. These findings could be due to ApoE essential role in circulation lipoprotein metabolism and key role in regulation of cholesterol impacting synaptic function maintenance; e4 allele carriers usually demonstrate higher dysfunction. Follow‐up analyses are required to substantiate current preliminary findings.
Elevation of membralin can improve the cognitive decline in 5xFAD mice
Authors: Jiang LuLin , Myers Stephanie , Shah Palak , Huang Huijie , Huang Timothy , Kaufman Randal J.
Published: December 2022

Background

Alzheimer’s Disease (AD) is the most prominent neurodegenerative dementia in the aging human population, with pathological hallmarks that include deposition of extracellular β‐amyloid (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). Aging is one of the largest risk factors for developing AD. Disturbed protein homeostasis is associated with the aging process. However, the cell‐type‐specific contribution of disturbed protein homeostasis to the aging process and AD progression is unclear. Our previous works identified a novel Endoplasmic‐Reticulum‐Associated Degradation (ERAD) component, membralin/TMEM259, which can mediate the turnover of nicastrin protein, consequently affect gamma‐secretase complex formation and activity. Knockdown membralin in an AD mouse model (TgCRND8) exaggerated beta‐amyloid‐associated neuronal damage. Moreover, selective deletion of membralin in astrocytes decreased excitatory amino acid transporter 2 (EAAT2) expression and induced neuroinflammation. Therefore, we hypothesized that elevation of membralin would improve beta‐amyloid‐associated cognitive decline and alleviate neuroinflammation.

Method

To investigate this, we generated a transgenic mouse line carrying the membralin gene, which expression was driven by a Prion promoter, and crossed this mouse line with 5XFAD mice. We performed behavioral studies using the Barnes Maze, Morris Water Maze, and Fear Conditioning tests on the 6‐month‐old animals. Biochemical and pathological analyses were used to determine the load of beta‐amyloid accumulation and neuroinflammation phenotype.

Result

Elevation of membralin improved spatial learning and memory in 5xFAD mice. Abeta 42 and Abeta 40 levels significantly reversely correlated with the membralin protein level. The abeta plaques appeared to be compact, and there were more microglia associated with the abeta plaques in the membralin transgenic animals crossed with the 5xFAD animals.

Conclusion

Overall, this suggests that elevation of membralin improves beta‐amyloid‐associated cognitive decline. And this could be partially from the effects of membralin in regulating neuroinflammation. Modulation of glial ER homeostasis could be a promising target to regulate neuroinflammation for AD therapy.
Strategies for diverse participant recruitment to a preclinical Alzheimer’s Disease prevention trial: The AHEAD study
Authors: Molina‐Henry Doris P. , Grill Joshua , Sperling Reisa A. , Aisen Paul , Clanton Taylor , Devins Theresa , Dhadda Shobha , Glover Crystal M , Irizarry Michael C , Johnson Keith A. , Kirn Dylan , Kramer Lynn D , Shum Leona K , Zhou Jin , Raman Rema
Published: December 2022

Background

Improving the demographic diversity of clinical trial participants, including preclinical Alzheimer’s disease (AD) trial participants, is a scientific, social, and ethical imperative.

Method

The AHEAD Study is an ongoing preclinical AD trial evaluating the efficacy of lecanemab (BAN2401) in biological and cognitive disease progression in cognitively unimpaired biomarker eligible individuals ages 55‐80. The study has an overall goal of at least 15% randomizations from underrepresented populations. The AHEAD Recruitment and Retention Workgroup designed a comprehensive and collaborative recruitment plan tailored to increase diverse participation.

Result

Recruitment strategies spanned central infrastructure and national initiatives, existing trial ready cohorts, enhanced site engagement, community outreach, and whenever possible, implementation of evidence‐based tactics. Central infrastructure includes a national call center, a study website with capacity for prescreening and site referral, including priority flags for underrepresented groups at the pre‐screener level; establishment of a website dedicated to Spanish speakers; and implementation of blood‐based screening across all sites and targeted communities. Site engagement approaches include disbursement of specialized funding to support local recruitment efforts tailored to diverse populations and the development of partnerships with community organizations or across sites within a region. Outreach activities, at the national, regional, and local level, include earned media and social media campaigns and award‐winning plays and videos surrounding themes of participation of diverse groups in clinical trials. Throughout, additional funding opportunities enable testing of innovative approaches and novel partnerships for recruitment of underrepresented groups at individual sites. Evaluation and additional support of these initiatives will be based on number of underrepresented participants pre‐screened, screened, and randomized in the study.

Conclusion

Focused, multipronged approaches and sustainable partnerships with demographically diverse communities are required to promote the participation of underrepresented groups into preclinical AD trials like AHEAD. Our initiatives demonstrate the commitment to increase recruitment of underrepresented groups by supporting successful efforts centrally, at the site‐level and the participant level using a combination of traditional and modern recruitment approaches.
Impact of the COVID‐19 Pandemic on Dementia Caregivers in the South US
Authors: Starks Takiyah D. , Lloyd Shawnta' , Caban‐Holt Allison M , Clark Jarrel , Byrd Goldie S.
Published: December 2022

Background

Compared to their non‐caregiving peers, caregivers of persons with dementia (PWD) endure higher psychological distress, social isolation and increased morbidity and disability. Stress and isolation experienced by caregivers during the COVID‐19 pandemic have added to caregiver burden and worsened health. The objective of this study was to obtain a greater understanding of the health and needs of informal caregivers of PWD during the COVID‐19 pandemic.

Method

Using a cross‐sectional questionnaire, we attained demographic data, characteristics of caregiving during the COVID‐19 pandemic, mental health status, COVID‐19 testing and illness, and protective measures taken to prevent infection with COVID‐19 among caregivers of PWD. From March 2021 to August 2021, respondents were recruited through the Maya Angelou Center for Health Equity’s Alzheimer’s disease (AD) registry. Descriptive statistics (frequency and proportions) of demographic, caregiving, health, and COVID‐19 related data for caregivers of PWD was conducted using SAS® software version 9.4.

Result

A total of 274 caregivers of PWD participated in the study. More than half of caregivers were women (56.57%), and approximately 73% of caregivers were married. The racial composition of the majority of caregivers included African American (44.16%), Non‐Hispanic White (26.64%), and Native American (20.44%). Most caregivers were providing care for parents (59.86%) or a partner (21.17%). Nearly 46% of caregivers reported experiencing stress, but not being burnt out. Almost 47% of caregivers reported high psychological distress during the COVID‐19 pandemic. In addition to caregiving stressors due to the COVID‐19 pandemic, caregivers also experienced behavioral changes in their household; more than half of caregivers experienced increased interpersonal conflict with loved ones, friends, or co‐workers. The top 3 needs reported during the COVID‐19 pandemic included support with caregiving, medical care, and food.

Conclusion

Approximately half of caregivers of PWD experienced stress and psychological distress during the COVID‐19 pandemic. In addition to the stress of caregiving, caregivers lacked support for necessary medical services and social needs. The data collected from caregivers during the COVID‐19 pandemic will be used to develop recommendations to support informal caregivers during emergency situations.
Prevalence of neuropsychiatric symptoms is greater in early‐ than late‐onset Alzheimer’s disease
Authors: Polsinelli Angelina J , Salazaar Krystal , Lane Kathleen A. , Gao Sujuan , Apostolova Liana G.
Published: December 2022

Background

Neuropsychiatric symptoms (NPS) present early in the disease course of Alzheimer’s disease (AD), increase in severity over time, and significantly affect patient and family quality of life. However, less clear is whether NPS may be more prevalent in early‐onset AD (EOAD) compared to late‐onset AD (LOAD).

Method

Data were obtained from the National Alzheimer’s Coordinating Center database. Baseline data from two groups – those with AD and those with a CDR of 0 at all visits (i.e., cognitively unimpaired [CU]) – were used for this analysis. Baseline was defined as the first time the individual was diagnosed with impaired cognition (AD) or the first evaluation (CU). Participants who completed the Neuropsychiatric Inventory Questionnaire were included. Participants who had additional neurological, systemic, psychiatric, or medical disease that could have significantly contributed to cognitive impairment were excluded. The AD group was divided into EOAD (< 65) or LOAD (≥65). The CU group was divided into early CU (< 65) or late CU (≥65) groups by age at evaluation.

Multiple logistic regression models were run for each NPS to examine its association with symptom onset (early or late), AD vs. CU, and onset*ADvsCU. All models were adjusted for sex, education, and disease severity (CDR‐SB). To explore the potential for medications to mask group differences, exploratory models were also run for each NPI symptom adjusting for psychotropic medication use.

Result

EOAD had higher rates of NPS than LOAD in almost all symptom categories (Figure 1). EOAD had significantly higher rates of elation, nighttime behavior and appetite/eating problems than LOAD relative to their CU age groups (p< 0.05). Younger age (age < 65) was associated with significantly higher prevalence of depression, anxiety, irritability, apathy, agitation, motor disturbance, and disinhibition (Table 1). Including medication use in these models did not change significance of results except for agitation (Table 1).

Conclusion

EOAD is associated with greater NPS burden than LOAD, and psychotropic medication use does not mitigate this association. Greater NPS load may significantly increase caregiver burden in this group. Future explorations will compare the association between disease progression and NPS severity in EOAD and LOAD.