bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroticism is the best predictor of lower emotional resilience during the COVID‒19‐related confinement periods
Authors: Gonneaud Julie , Paly Léo , Delarue Marion , Mézenge Florence , Fauvel Séverine , Lefranc Valérie , Cognet Aurélia , de Flores Robin , Touron Edelweiss , Marchant Natalie L , Poisnel Géraldine , Chetelat Gaël ,   the Medit‐Ageing Research group
Published: December 2021

Background

The COVID‐19 pandemic and the associated distancing measures dramatically affect psychoaffective health, and this is accentuated in older adults who are more vulnerable to the situation. In this study, we are interested in the predictors of emotional resilience in healthy older adults, and also on how the repetition of confinement periods could influence this resilience and its predictors.

Method

102 cognitively unimpaired older adults from the Age‐Well cohort were included. They all completed the Depression Anxiety Stress Scales (DASS‐42) during each period of national confinement (April and November 2020), used here as a measure of emotional resilience (lower scores indicating greater resilience). Baseline measures from the Age‐Well study, all acquired before the pandemic, were used as predictors, including demographics (age, sex, education), personality (Big Five Inventory), psychological (anxiety [STAI‐B], depression [GDS]), lifestyle (Lifetime of experience questionnaire), global cognitive functioning (Mattis‐DRS) and neuroimaging data (hippocampal volume, brain perfusion, amyloid burden). We ran stepwise regressions to predict emotional resilience during the first confinement. Then, we used paired t‐test to assess the evolution of emotional resilience between the two confinements. Finally, we replicated the stepwise regressions to predict changes in resilience over time ('second‐minus‐first' confinement).

Result

Neuroticism was the only significant predictor of the DASS‐42 score during the first confinement (β=.48; p<.001; Figure‐1), lower neuroticism being associated with better resilience. We found the DASS‐42 score to increase significantly from the first to the second confinement, indicating decreased emotional resilience over time. Moreover, higher neuroticism (β=.53; p<.001) and higher agreeableness (β=.20; p=.03) were associated with higher DASS‐42 increase over time (Figure‐2).

Conclusion

Our study suggests that lower neuroticism is the main predictor of greater emotional resilience to the COVID‐19‐related confinement. Importantly, the repetition of the confinement situation is associated with a decrease in emotional resilience in older adults, especially if they are prone to experience distress (neuroticism) or have a particularly social personality (agreeableness). Overall, these results underline the increasing need, as the crisis persists, for a psychoaffective support of older adult.
A remote digital tool for diagnosis and monitoring of Alzheimer’s disease
Authors: Modarres Mohammad Hadi , Kalafatis Chris , Apostolou Panos , Marefat Haniye , Khanbagi Mahdiyeh , Karimi Hamed , Vahabi Zahra , Aarsland Dag , Khaligh‐Razavi Seyed‐Mahdi
Published: December 2021

Background

Early detection and monitoring of mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) patients are key to tackling dementia and providing benefits to patients, caregivers, healthcare providers and society.

Method

We developed the Integrated Cognitive Assessment (ICA); a 5 minute computerised cognitive test employs Artificial Intelligence (AI) to improve its accuracy in detecting cognitive impairment. ICA presents a series of rapidly changing images on a mobile device to measure cognitive impairment via a person's accuracy and response time in categorising those images.

We studied the ICA in a total of 230 participants. 95 healthy volunteers, 80 MCI, and 55 mild AD participants completed the ICA, the Montreal Cognitive Assessment (MoCA) and Addenbrooke’s Cognitive Examination (ACE) cognitive tests.

Result

The ICA demonstrated convergent validity with MoCA (r=0.58) and ACE (r=0.62). The ICA AI model was able to detect cognitive impairment with an area under the curve of 81% for MCI patients (MoCA 77%), and 88% for mild AD patients (MoCA 89%). The AI classifier, based on an explainable logistic regression model, demonstrated improved performance with increased training data. Furthermore it showed generalisability in performance from one population to another. The ICA was able to detect cognitive impairment with high accuracy when trained with one cohort and tested in an independent cohort with different cultural and demographic characteristics, a prerequisite for large population deployment.

In a monitoring study, 12 healthy participants self‐administered 78 ICA tests remotely over a period of 3 months (936 tests in total). The ICA demonstrated no significant practice effect observed over the duration of the study.

Conclusion

The ICA can support clinicians by aiding accurate diagnosis of MCI and AD and is appropriate for large‐scale screening of cognitive impairment. The ICA is unbiased by differences in language, culture and education and has additional advantages over standard of care tests because of its shorter duration, automatic scoring and potential for medical record or research database integration.

The pandemic has presented a challenge for face‐face assessments. A digital tool such as the ICA allows us to adapt to these changes by administering assessments remotely and monitoring disease progression.
Memory markers can help trace the Alzheimer’s disease continuum: Evidence from the GERO Cohort
Authors: Forno Gonzalo , Parra Mario A , Lillo Patricia , Villagra Roque , Parrao Teresa , Thumala Daniela , Slachevsky Andrea
Published: December 2021

Background

Cognitive assessments able to detect impairments as early as neuropathological changes that occur in neurodegenerative diseases initiate are urgently needed. The Visual Short‐Term Memory Binding Test (VSTMBT) and the Free and Cued Selective Reminding Test (FCRST) have been recently recommended by the Neurodegenerative Diseases Working Group (Costa et al., 2017) as promising preclinical markers of AD. They have never been used before to assess elderlies with cognitive complain recruited from the community.

Method

A total of 271 subjects (37 healthy controls (HC), 112 subjective cognitive complain (SCC), 96 mild cognitive impairment (MCI) and 26 Alzheimer’s disease dementia (ADD)), recruited from Geroscience Center for Brain Health and Metabolism (GERO) Cohort and the Memory and Neuropsychiatric Clinic (CMYN), underwent assessment with the VSTMBT and the Visual Version of the FCRST (FCRST‐Visual). Two memory loads were used for the VSTMBT (low and high). The ability of these tests to discriminate between groups.

Result

Significant differences were found between HC, MCI and ADD using the VSTMBT and the FCRST‐Visual version. Notably, the STMB was the only test that “marginally” differentiated between HC from SCC (p = 0.055). Moreover, whereas the FCRST‐Visual showed a gradient (HC = SCC) > MCI > AD, the VSTMBT’s gradient was HC > (SCC = MCI = ADD) suggesting that the function assessed by the latter test may be sensitive to the very early stages of the disease dropping to levels that cannot decline further.

Conclusion

Our results suggest that the VSTMBT and FCSRT are sensitive to the early stages of dementia. Whereas the former detects changes in the early subjective stages, the latter is more sensitive to later objective stages of cognitive decline. The latter but not the former could help monitor disease progression. These results raise important questions about the usefulness of cognitive screening tools to detect and monitor disease progression and to separate normal and abnormal ageing trajectories. We propose the need of cognitive assessments that detect subtle differences as early as neuropathological changes occur in the brain, which will lead to the development of new “cognitive biomarkers” for dementia.
Examining older adults’ perceived workload, motivators, and barriers experienced during an exergame study — a mixed methods approach
Authors: Crane Breanna M , Drazich Brittany , Moored Kyle D , Taylor Janiece , Carlson Michelle C
Published: December 2021

Background

There is increasing interest in using exergames to promote physical and cognitive functioning. Examining the perceived workload and various motivators/barriers associated with enrollment and retention in exergame studies is needed to design engaging and sustainable exergame interventions. In this study, we examined the perceived workload, motivators, barriers, and general feedback from older adults participating in an exergame study.

Method

We conducted 3 semi‐structured focus groups among 14 older adults from a senior living center to evaluate motivators and barriers associated with joining and remaining in the Stimulation with Intricate Movements (SWIM) study. The SWIM study was designed to assess the impact of an exergame called “Bandit the Dolphin” which simultaneously integrates cognitive and physical activity within an immersive, interactive environment. The NASA‐TLX scale was used to assess perceived workload during gameplay, and ratings ranged from 0‐100 (low to high workload). An exit survey assessed participants’ experiences and perceived changes in activity following the study (e.g., social, cognitive, physical).

Result

Motivators for joining were self‐improvement, generativity, peer referrals, and curiosity. Motivators for retention involved immersion during gameplay, gaining a sense of accomplishment, and exercise. Barriers included exhaustion/pain from standing and frustration from lack of level advancement. Perceived effort [M=62.5,SD=13.0] and physical demand [M=57.9,SD=13.8] were the highest ranked categories on the NASA‐TLX scale, followed by mental demand [M=49.3,SD=17.2]. Frustration received the lowest ranking [M=37.9,SD=26.5]. From the exit survey, 100% would recommend the study to a friend, 53% said participating in the study changed their physical activity levels, and 40% reported changes in their comfort with video games/technology.

Conclusion

Primary motivators for study initiation and retention align with the Self‐Determination Theory which posits intrinsic motivation arises when autonomy, competence, and social relatedness are achieved. NASA‐TLX results show that perceived effort and physical demand of gameplay ranked highest, followed by mental demand, with frustration ranking the lowest. Notably, all participants would recommend the study to a friend. Overall, participants perceived “Bandit the Dolphin” as a cognitively and physically demanding, enjoyable, and effortful exergame. These results will guide future efforts to design engaging and sustainable exergames aimed at improving cognitive and functional health among older adults.
Impact of baseline daily physical activity on cognitive and physical effects of lifestyle multidomain intervention: The SUPERBRAIN study
Authors: Choi Muncheong , Song Hong‐sun , Chun Buong‐O , Lee Sun Min , Hong Chang Hyung , Park Yoo Kyoung , Na Hae Ri , Kim Byeong C. , Park Kyung Won , Park Hee Kyung , Jeong Jee Hyang , Choi Seong Hye , Moon So Young
Published: December 2021

Background

In the South Korean study to prevent cognitive impairment and protect brain health through lifestyle intervention in at‐risk elderly people (SUPERBRAIN), we explored impact of baseline daily physical activity on cognitive and physical effects of 24‐week lifestyle multidomain intervention.

Method

A total of 152 participants, aged 60‐79 years without dementia but with ≥ 1 modifiable dementia risk factor, were randomly assigned to the facility‐based multidomain intervention (FMI), and home‐based MI (HMI), or control groups. Among them, 82 participants (27 FMI, 34 HMI, and 21 control) took their physical activity for 7 days using the accelerometer (Actigraph GT3X+, FL, USA) at baseline. We divided 61 participants in the FMI or HMI into two groups according to their physical activity at baseline: Group I who met WHO physical activity guidelines for older adults (more than 150 minutes of moderate activity per week) and Group Ⅱ who did not meet the guidelines. We compared changes of cognitive and physical measures after 24‐week intervention between group I and Group Ⅱ. Cognitive function was measured using the total sale index score of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the physical fitness was measured by the hand grip strength test, 30 s sit‐to‐stand test, 3 m sit–walk‐and‐return test, sit‐and‐reach test, 2‐min stationary march, and Figure‐8‐walks. Due to not satisfying the normality test, the nonparametric tests Mann‐Whitney and Wilcoxon were analyzed using IBM SPSS Statistics25.

Result

Groups I and II had no significant difference in the baseline total sale index score of the RBANS, whereas the group I had a higher physical fitness at baseline (sit‐and‐reach test and 3m sit‐walk‐and‐return test <0.05; Figure‐8‐walks <0.01). After the intervention, only Group I showed significant improvement in the total sale index score of the RBANS. Both groups were significantly improved in 30 s sit‐to‐stand test, 2‐min stationary march, and Figure‐8‐walks. However, hand grip strength was improved in only Group I.

Conclusion

Significant improvement in both cognitive and physical function in at‐risk but active elderly without substantial impairment in the SUPERBRAIN suggest that preventive strategies may be more beneficial on cognitive and physical function in active older adults.
A post‐mortem study of melanin‐concentrating hormone (MCH) neurons in Alzheimer’s disease and progressive supranuclear palsy: The complex degeneration pattern of the lateral hypothalamic area
Authors: Mladinov Mihovil , Oh Jun Yeop , Petersen Cathrine , Eser Rana April , Li Song , Theofilas Panos , Spina Salvatore , Seeley William W. , Bittencourt Jackson Cioni , Neylan Thomas , Grinberg Lea T.
Published: December 2021

Background

Melanin‐concentrating hormone neurons (MCH) are a key component of the subcortical brain circuits controlling sleep and wake states, and integrating them with other vital functions like motivated and feeding behavior into a 24‐hour circadian rhythm. Together with orexinergic neurons (OX), they represent the major neuronal population of the lateral hypothalamic area (LHA). Our group previously reported a profound degeneration of OX neurons in Alzheimer's disease (AD), and a reduction of OX production in progressive supranuclear palsy (PSP). In this report we provide for the first time a comprehensive and quantitative morphological study of MCH neurons in patients with AD, PSP and normal controls.

Method

Post‐mortem human brain tissue of subjects with AD, PSP and controls was examined using unbiased stereology. Double immunohistochemistry with MCH‐ and tau‐antibodies on formalin‐fixed, celloidin embedded tissue was performed.

Result

There was no significant difference in the total number of MCH neurons between AD, PSP and controls, but a significant loss of non‐MCH neurons in AD patients (p=0.019). The proportion of MCH neurons was significantly higher in AD (p=0.0047). No such a difference was found in PSP. In PSP, but not AD, the proportion of tau+ MCH neurons was lower than the proportion of tau+ non‐MCH neurons (p=0.002). When comparing AD to PSP, the proportion of tau+MCH neurons was higher in AD (p<0.001).

Conclusion

High burden of tau‐inclusions, but comparably milder loss of MCH neurons in AD, together with previously reported orexinergic neuronal loss may lead to a hyperexcitability of the MCH system in AD. This may contribute to the well‐known impairment of vigilance, reduction of NREM sleep and REM sleep disruption in AD. In contrast, we found virtually no involvement of MCH neurons in PSP, which reflects a specific vulnerability of these neurons to AD pathology. Clinically, PSP features a hyperarousal state, indicating that the activity of the arousal system prevails over a deficient sleep promoting system. We conclude that the involvement of other sleep promoting nuclei contributes to the insomnia in PSP. Further experimental research is needed to understand the molecular pathways involved in the specific vulnerability of MCH neurons in AD.
Plant‐based dietary patterns and cognitive function in U.S. adults: A prospective evaluation
Authors: Liu Xiaoran , Wang Yamin , Dhana Klodian , Agarwal Puja , Cherian Laurel J , Bennett David A. , Schneider Julie A. , Aggarwal Neelum T.
Published: December 2021

Background

A plant‐based dietary patterns focus on foods primarily from plant sources. However, not all plant‐based foods are necessarily beneficial for health. We aim to examine the relationship between plant‐based diet quality and cognitive function.

Method

Analyses were conducted among 701 participants from the Memory and Aging Project. Food Frequency Questionnaires (FFQ) were incorporated into the studies in 2004 and collected annually thereafter. Individuals with mild cognitive impairment, missing food‐frequency questionnaire (FFQ) at baseline, extreme BMI, and less than two cognitive assessments during 10 years of follow‐up were excluded for these analyses. Plant‐based diet quality were assessed by 3 plant‐based diet indices (score range, 18‐90) including 1) an overall plant‐based diet index (PDI) by assigning positive scores to all plant foods and reverse scores to animal foods; 2) a healthful PDI (hPDI) where positive scores were given to only healthy plant foods, less‐healthy plant foods and animal foods received reverse scores; 3) an unhealthful PDI (uPDI), where less‐healthy plant foods received positive scores and animal and healthy plant foods received reverse scores. Our primary outcome was composite global cognition z score. We used liner mixed model examining the association between PDI (as a continuous and categorical) and cognitive decline.

Result

Higher hPDI was associated with a better cognitive functioning during follow‐up. Compared to individuals in the first tertile of hPDI, individuals in the third tertile had slower cognitive decline by 0.03 units per year (β = 0.03, p=0.017). Similarly, when we evaluated the hPDI as continuous variable, each10‐points increase in hPDI was associated with 0.01 units/year slower cognitive decline. In contrast, higher adherence to uPDI was associated with faster cognitive decline. Individuals in the third tertile of uPDI had a faster decline by 0.04 unites per year (β = 0.04 , p=0.017). Every 10‐point increase in uPDI was associated with a 0.01 unit per year faster cognitive decline.

Conclusion

Higher intake of a plant‐based diet index rich in healthier plant foods was associated with slower cognitive decline. This supports current recommendations to shift to diets rich in healthy plant foods, with lower intake of less healthy plant and animal foods.
Biomarkers for Alzheimer’s disease in Black populations: A scoping review
Authors: Moeller Stacey , John Samantha E
Published: December 2021

Background

Black/African American (B/AA) older adults have roughly double the risk of developing Alzheimer’s disease (AD) and greater risk for being undiagnosed compared to non‐Hispanic whites (NHW)(2020 Alzheimer’s Disease Facts and Figures). There is a dearth of research on AD biomarkers in the B/AA community. Biomarkers identify those at risk for or in the preclinical stages of AD, establish clinical trial eligibility, and inform diagnosis and treatment. This study reviews current literature on AD biomarkers in the B/AA population.

Method

A scoping review was conducted of B/AA study samples that examined three widely accepted AD biomarkers and the risk of disease conferred by each. Apolipoprotein E (APOE) and the e4 allele, cerebrospinal fluid (CSF) values of aBeta and tau, and amyloid positron emission tomography (PET) were included. Articles were reviewed independently by two researchers using the Colquhoun et al. (2014) method.

Result

Initial searches yielded 326 APOE results, 46 CSF, and 33 amyloid PET. After review, 64 remained for APOE, 4 for CSF, and 8 for amyloid PET. Within APOE, e4 presence conferred similar (Graff‐Radford 2002; Sawyer 2009) or lower (Evans 2003; Rajabli 2018) AD risk in B/AA versus NHW, with no consensus on the protection offered by e2 (Allred 2016; Graff‐Radford 2002). CSF literature highlighted that B/AA had lower levels of total tau and phosphorylated tau 181 (Morris 2019; Howell 2017; Garrett 2019), with lower (Garrett 2019; Howell 2017) or similar (Morris 2019; Babulal 2020) levels of beta amyloid. In amyloid PET, B/AA amyloid burden was similar (Morris 2019; Amariglio 2020) to or above (Gottesman 2016; Hughes 2018) NHW, but longitudinal investigation suggested faster decline among B/AA (Amariglio 2020). The role of APOE e4 in amyloid burden is incompletely understood. One study found increased amyloid in both races (Morris 2019) among e4 carriers, while another study identified greater amyloid among B/AA even after adjusting for APOE status (Gottesman 2016).

Conclusion

Unique AD biomarker profiles among B/AA relative to NHW may be a contributor to diagnostic inequities across groups, particularly missed or late diagnoses among B/AA. These differences warrant in‐depth investigation and highlight the need for inclusive outreach and engagement approaches in research.
Subjective cognitive complaints in Chinese‐ and English‐speaking older adults
Authors: Li Clara , Zeng Xiaoyi , Yang Xiao , Zhu Carolyn W , Neugroschl Judith A. , Aloysi Amy , Cai Dongming , Martin Jane , Sewell Margaret , Loizos Maria , Greenberg Jonathan , Xu Mengfei , Evans Kirsten , Pun Kelly , Tocco Carly , Ardolino Allison , Meuser Caroline , Sheppard Faye , Gamino Juliana , Velasco Nelly , Sano Mary
Published: December 2021

Background

Research increasingly suggests that subjective cognitive complaints (SCC) in cognitively healthy older adults may be a harbinger of cognitive decline and dementia. However, there is virtually no investigation on SCC across language groups (English and Chinese). This study examines SCC in Chinese American older adults who are monolingual Chinese speakers. This population has a high risk of being misdiagnosed with cognitive loss and dementia due to cultural and language barriers.

Method

The Alzheimer’s Disease Research Center at Icahn School of Medicine at Mount Sinai evaluates diverse older adults using the National Alzheimer’s Coordinating Center’s Uniform Data Set. Each participant receives a research diagnosis of normal control, mild cognitive impairment, and dementia at consensus. SCC was measured by the Cognitive Function Instrument (CFI). The instrument covers changes in cognition with yes(1)/no(0)/maybe(0.5) as available responses. Total score ranges from 0 to 14, with higher scores indicating greater SCC. The development of Chinese version of CFI was modeled after a protocol for multinational translations, which includes two independent forward translations and a back translation. Multivariate analysis of variance was conducted to examine group differences in SCC using CFI scores as dependent variables, while accounting for age, gender, and education.

Result

Data analysis included English‐ (n=63) and Chinese‐speaking older adults (n=30) who received a diagnosis of normal cognition, with no psychiatric symptoms/diagnosis at consensus. The two groups did not differ in age (Chinese=73.43+6.83 years; English=74.75+7.12 years) and gender (Chinese=70.0% female; English=65.1% female), but Chinese‐speaking older adults (13.83+3.12 years) had lower levels of education compared to English‐speaking older adults (16.49+2.47years). Results show that Chinese‐speaking older adults endorsed more SCC (3.52+2.68 items) than English‐speaking older adults (1.74+1.67 items) (p<0.01). For 7 of the CFI items (i.e., rely more on written reminders, need help to remember appointments, trouble driving, less social, trouble following news/TV/books, difficulty with hobbies/activities, become disoriented/get lost), frequency of endorsement was higher in Chinese‐speaking older adults than English‐speaking older adults (p<0.05).

Conclusion

Our findings highlight potential differences in SCC reported by Chinese‐speaking older adults who have immigrated to the USA. A longitudinal follow up is needed to evaluate contributing factors to such differences.
Mapping associations across multiple aspects of Alzheimer disease and the role of CSF biomarkers in individuals without dementia
Authors: Waterink Lisa , Zwan Marissa D. , Barkhof Frederik , de Boer Casper , Ingala Silvia , Lorenzini Luigi , Muñiz‐Terrera Graciela , Ritchie Craig W. , Visser Pieter Jelle , van der Flier Wiesje M , Teunissen Charlotte E. , van Deun Katrijn , Vermunt Lisa ,   for the EPAD Consortium
Published: December 2021

Background

Alzheimer disease (AD) is a complex disorder involving biological, clinical, and lifestyle aspects. Assessing all these aspects simultaneously allows to better disentangle the position of CSF marker abnormalities across AD stages. Here, we employ a novel statistical method specifically developed to reveal meaningful associations across multiple aspects that can occur simultaneously within individuals.

Method

We selected the baseline data from the European Prevention of Alzheimer Disease cohort of individuals without dementia (www.ep‐ad.org; n=1243, mean±SD age = 65±7 years old, 57% female, 18% CDR ≥0.5) covering ten aspects: demographics including APOE‐genotype, cerebrospinal fluid (CSF) biomarkers, MRI visual rating scales, MRI regional volumes, MRI white matter lesions, cognition, function, psychological factors, general physical health, and comorbidities. We used regularized simultaneous component analysis (regSCA), a statistical technique that extracts relevant components which explain variation within and across these aspects, and robustly selects the appropriate variables [1, 2].

Result

The optimal model revealed eight components explaining 51% of the total variance. Figure 1 presents an overview of all components, showing the strengths and directions of the associations between variables. Five components included CSF biomarkers, which were (1) Abeta42‐dominant, (2) Tau‐dominant, (3) function‐dominant, (4) age‐dominant and, (5) white matter lesion‐dominant. In (3) and (4), Abeta42 and Tau related to cognition and function. Only (3) was independent of age, and may represent purely AD. In (5), Abeta42 related to white matter lesions, and may represent the degree cerebral amyloid angiopathy (CAA). Abeta42 in (1) and Tau in (2) related to APOE‐genotype, suggesting these may be independent effects. The three components unrelated to CSF biomarkers were: (6) sex‐dominant, (7) psychological factors‐dominant, and (8) life‐style‐only.

Conclusion

Analysis of robust associations across multiple aspects of AD simultaneously implicated CSF biomarkers in five components. These components may represent risk‐profiles and AD disease processes in cognitively normal and mildly impaired individuals. Our next step is to investigate the stability of the components and their co‐expression within individuals. This overview of complex relationships between AD‐related aspects, helps to understand the disease mechanisms in of AD. This novel approach can be a solution for analyses of large and complex datasets in AD.
The effect of a mindfulness‐based versus health self‐management intervention on cognitive performance in older adults with subjective cognitive decline (SCD): The SCD‐Well randomized controlled trial
Authors: Whitfield Tim , Demnitz‐King Harriet , Schlosser Marco , Barnhofer Thorsten , Collette Fabienne , Dautricourt Sophie , Delarue Marion , Frison Eric , Gonneaud Julie , Klimecki Olga M , Lutz Antoine , Paly Léo , Poisnel Géraldine , Salmon Eric , Schild Ann‐Katrin , Walker Zuzana , Wirth Miranka , Chetelat Gaël , Jessen Frank , Marchant Natalie L ,   The Medit‐Ageing Research Group
Published: December 2021

Background

Subjective cognitive decline (SCD) denotes self‐reported cognitive concerns in the absence of objective cognitive impairment. Individuals with SCD convert to dementia at twice the annual rate of healthy controls, with relatively poorer cognition in SCD conferring additional risk. Non‐pharmacological interventions are currently undergoing intensive evaluation for promoting cognitive function in SCD.

Method

This study utilized data from the SCD‐Well randomized controlled trial. One hundred forty‐seven older adults with SCD, recruited from clinics in four European countries, were randomized to one of two 8‐week non‐pharmacological interventions: the Caring Mindfulness‐Based Approach for Seniors (CMBAS), or a Health Self‐Management Program (HSMP). Participants’ objective cognitive performance was assessed at baseline, post‐intervention, and 24‐weeks follow‐up using a battery of tests. Four of these (RAVLT, WAIS‐IV Coding, Mattis DRS‐2 and Category Fluency) were combined to yield an abridged version of the Preclinical Alzheimer’s Cognitive Composite 5 (PACC5Abridged). Linear mixed models estimated the change in outcome measures (the PACC5Abridged and its constituents) within and between arms. All models were adjusted for country and participant demographics (sex, age, and education), as well as the time‐varying effect of participants’ repeated practice with the outcome measures.

Result

There was a statistically significant improvement in the PACC5Abridged in both arms of the trial (p<.001), which did not differ between groups. The mean change in PACC5Abridged from baseline to 24‐weeks was 0.28 for CMBAS, and 0.22 for HSMP (pooled baseline SD 0.72). The effect of participants’ repeated practice on the PACC5Abridged was non‐significant, ruling out retest effects as a substantive explanation for results. Amongst the PACC5Abridged constituent tests, significant improvement was observed in the RAVLT and WAIS‐IV Coding.

Conclusion

This clinical trial evaluated the effect of two 8‐week non‐pharmacological interventions on objective cognitive performance in SCD. Scores on a composite measure of early Alzheimer’s disease related cognitive dysfunction improved in both arms, even after accounting for practice effects. These results paralleled those of the primary outcome measure (trait anxiety), for which scores also improved in both arms. This work adds to the growing body of evidence that non‐pharmacological interventions can impact cognition in individuals at increased risk of dementia.
Alzheimer’s disease mortality high in rural areas in South: 1999‐2019
Authors: Kulshreshtha Ambar , Ramer Stephanie , Cato Sarah , Hajjar Ihab
Published: December 2021

Background

Urban‐rural differentials exist in the United States for both socio‐economic and cultural reasons. Geographic variation in Alzheimer’s mortality exist, but how it applies to specific urbanization levels has not been examined previously. We sought to describe the pattern and magnitude of urban‐rural variations in Alzheimer’s mortality in the United States.

Methods

We used data from the National Center for Health Statistics to examine trends in Alzheimer’s death rates (ICD‐10 codes G30) between 1999 and 2019 by urbanization levels. Alzheimer’s mortality was defined as death from Alzheimer’s in over the age of 65 years using data from death certificates. Urbanization classification is per 2013 NCHS definitions. Crude and age‐adjusted changes in Alzheimer’s mortality rates were calculated in the overall population and in specific urbanization groups: in large and medium metros (urban); and non‐metros (rural). We also examined differences by race and sex. Poisson regression was used to model data.

Results

From 1999‐2019, the age‐adjusted mortality rate from Alzheimer’s has increased significantly from 16 to 30 deaths per 100,000, an 88% increase. Significant disparities by urbanization and census region exist. Mortality rates are highest in the rural areas in the East South‐Central region, where the death rate from Alzheimer’s is 274 per 100,000 in those over 65. Mortality rates are lowest in urban areas in the Mid‐Atlantic region, where the death rate is 86 per 100,000. Trends over time show a widening disparity across region and urbanization. Women had higher age‐adjusted AD mortality rates than men, regardless of metro area or race.

Conclusions

Rural areas particularly in South are experiencing a disproportionate burden of Alzheimer’s disease mortality. The reason for this trend might be manifold and related to access to primary care, timely diagnosis, and the rising proportion of older Americans living in these areas. Identifying and understanding the underlying causes of disparities in AD mortality among communities is key in designing targeted public health policies and interventions to curb the epidemic.
A cognitive composite for genetic frontotemporal dementia: GENFI‐cog
Authors: Poos Jackie M. , Nicholas Jennifer M , Moore Katrina M , Russell Lucy L , Peakman Georgia , Jiskoot Lize C. , van den Berg Esther , Papma Janne M. , Seelaar Harro , Pijnenburg Yolande A.L. , Moreno Fermin , Sanchez‐Valle Raquel , Borroni Barbara , Laforce Robert , Masellis Mario , Tartaglia Maria Carmela , Graff Caroline , Galimberti Daniela , Rowe James B , Finger Elizabeth , Synofzik Matthis , Vandenberghe Rik , Mendonca Alexandre , Tagliavini Fabrizio , Santana Isabel , Ducharme Simon , Butler Christopher , Gerhard Alexander , Levin Johannes , Danek Adrian , Otto Markus , van Swieten John C , Rohrer Jonathan D
Published: December 2021

Background

Development of endpoints for clinical trials in frontotemporal dementia (FTD) is increasingly urgent. In other neurodegenerative diseases composite scores are often used as outcome measures but are, as of yet, lacking in FTD. The aim of this study was to create gene‐specific cognitive composite scores for MAPT, GRN and C9orf72 mutation carriers and provide recommendations on recruitment and trial duration.

Method

69 C9orf72, 41 GRN, 28 MAPT mutation carriers with a CDR® plus NACC‐FTLD global score ≥0.5 and 275 controls completed a neuropsychological battery covering five cognitive domains. Logistic regression was used to identify the combination of tests that discriminated best between mutation carrier groups and controls. Weighted averages of the test scores in the models were calculated based on the regression coefficients (GENFI‐cog). Sample size estimates were calculated for individual tests and composite. The treatment effect was estimated as the mean difference between CDR® plus NACC‐FTLD 0.5 and 1 groups. Time‐to‐event analysis was used to determine the fraction of patients within GENFI that converted from CDR® plus NACC‐FTLD 0.5 to ≥1.

Result

The most sensitive model in C9orf72 mutation carriers included a combination of executive, social cognitive and visuoconstructive tests (Table 1). A combination of executive, social cognitive, semantic and memory tests was most sensitive in GRN mutation carriers, and a combination of social cognitive, attention, semantic and memory tests in MAPT mutation carriers, resulted in the most sensitive model. The estimated sample size to detect a treatment effect was lower for the composite than for most individual tests (Table 2). A Kaplan‐Meier curve (Figure 1) showed that after three years 50% of individuals convert from CDR® plus NACC‐FTLD global score 0.5 to 1 or more.

Conclusion

We created gene‐specific cognitive composite scores for C9orf72, GRN and MAPT mutation carriers (GENFI‐cog) which resulted in substantially lower estimated sample sizes to detect a treatment effect than most individual cognitive tests. Only 50% of patients with a CDR® plus NACC‐FTLD of 0.5 convert to ≥1 in a three‐year period. GENFI‐cog has potential as a cognitive endpoint for upcoming trials and the results from this study provide important information concerning trial duration and sample sizes.
Feasibility of treating hearing loss to prevent dementia in MCI: Results of the face to face and remote interventions in the Treating Auditory impairment and Cognition Trial (TACT)
Authors: Gonzalez Sergi Costafreda , Bamiou Doris‐Eva , Lewis Glyn , Livingston Gill , Omar Rumana , Pavlou Menelaos , Proctor Danielle , Schilder Anne
Published: December 2021

Background

Age‐related hearing loss is an independent and potent risk factor for dementia. There is observational evidence that hearing aid use may mitigate deterioration in cognitive performance and could prevent dementia, but experimental evidence is lacking. A trial on whether treating hearing loss reduces the risk of dementia may not be feasible because people often do not access or use hearing aids even when prescribed. We designed the Treating Auditory impairment and Cognition Trial (TACT) as a manual‐based preventative intervention, promoting and supporting hearing aid use in those with Mild Cognitive Impairment. We studied the feasibility of a full‐scale randomized controlled trial.

Method

We conducted a pilot trial of a new intervention designed to increase uptake and adherence to hearing aid treatment. Pre COVID‐19, we randomized MCI participants to face‐to‐face interventions: the active arm is a home‐based hearing assessment and hearing aid fitting, with study audiologist and research assistant delivering motivational and practical support in 4 visits over 3 months. Participants in the control arm were referred to standard audiological care through their general practitioner without additional hearing support, and given a healthy ageing educational intervention on dementia risk factors, matched in contact with the study team. Follow‐up for both interventions was at 6 months. After the onset of COVID‐19, additional MCI participants, who had not received hearing aids, were allocated to active remote hearing support. This did not involve any face‐to‐face contact with the study team but provided hearing support remotely, with outcomes collected after 1 month.

Result

Pre COVID‐19, N=36 MCI participants were randomized to the original face‐to‐face study interventions, with follow‐up measures collected at 6 months, also in a face‐to‐face session. After the onset of COVID‐19, a further N=11 received the remote hearing intervention. We will present results from these samples. The pre‐specified outcomes of the pilot include recruitment, randomization, retention, and acceptability of the interventions, with secondary outcomes including difference in usage of hearing aids between active and control arms, and cognition, mood, and social function.

Conclusion

The results of this study may influence hearing care in all settings as well as dementia prevention.
Association between APOE‐ε4 allele and CSF amyloid in memory performance differ by sex
Authors: Brugulat‐Serrat Anna , Tsoy Elena , Milà‐Alomà Marta , Sánchez‐Benavides Gonzalo , Buckley Rachel F. , Gispert Juan Domingo , Molinuevo Jose , Possin Kate L , Kramer Joel H ,   EPAD Consortium
Published: December 2021

Background

There is growing evidence of sex differences in the association between Alzheimer’s disease (AD) biomarkers and cognition. However, few studies have examined the effect of sex on the associations between established AD risk factors and cognitive performance in clinically normal older adults. This study aimed to elucidate potential sex differences in the relationship between APOE‐ε4 status, AD biomarkers, and cognitive performance in a large multinational cohort of clinically normal older adults.

Method

Participants were 952 cognitively unimpaired older adults from the multicenter European Prevention of Alzheimer’s Disease (EPAD) study (age range 50‐88 years, mean age 65.0(7.0), mean education 14.6(3.6) years, 58% females). All participants underwent a lumbar puncture and CSF Aβ42, p‐tau and t‐tau biomarkers (Roche Elecsys®) were measured, APOE genotyping, and a battery of digital cognitive tests (UCSF TabCAT; Favorites (associative memory), Dot Counting (executive function), and Flanker (processing speed)). APOE genotype was dichotomized (ε4 carrier vs. ε4 non‐carrier). We performed multiple linear regression models to examine the effect of sex, CSF biomarkers, APOE‐ε4, and their interactions on cognitive performance covarying for age, education, and testing language.

Result

There were no differences in age (p=.07), frequency of APOE‐ε4 carriers (33.1%, p=.55) or CSF biomarkers (all p>0.1) between males and females. Females had lower educational attainment (p=.01). Females outperformed males on an associative memory task (p=.002), whereas males performed better on tasks of working memory (p=.01) and inhibitory control (p=.01). A sex*Aβ*APOE‐ε4 status interaction (p=.01) revealed APOE‐ε4 carriership and abnormal levels of CSF Aβ were associated with poorer associative memory performance only in males (Fig 1).

Conclusion

Sex seems to moderate the association between CSF Aβ and APOE‐ε4 allele and memory performance in cognitively unimpaired older adults. Our results suggest a cross‐sectional association of APOE‐ε4 and CSF Aβ with cognitive performance in males that complement previous literature on the relationship between APOE‐ε4 and longitudinal cognitive decline in females. Taken together, these findings highlight the importance of understanding the complexity of sex differences in individuals at higher risk of AD.
Memory training in older adults with mild cognitive impairment: Positive effects are found five years after MEMO training compared to control intervention
Authors: Belleville Sylvie , Cuesta Marc , Bier Nathalie , Brodeur Catherine , Gauthier Serge , Gilbert Brigitte , Grenier Sébastien , Ouellet Marie‐Christine , Viscogliosi Chantal , Hudon Carol
Published: December 2021

Background

Cognitive training was found to have a positive effect on the memory of healthy older adults, including long‐term benefits (Rebok et al, 2014). This finding offers hope that cognitive training could contribute to prevention approaches. However, little is known regarding the long‐term benefits of cognitive training in older adults with mild cognitive impairment (MCI), many of whom are in the early phase of Alzheimer’s disease. In a prior randomized controlled trial (Belleville et al, 2018), we reported a short‐term benefit of cognitive training on the delayed recall of older adults with MCI. The objective of this study was to assess the impact five years later.

Method

This is the five‐year follow‐up of a single‐blind randomized controlled trial (MEMO+). Participants with amnestic MCI were randomized to memory training or an active (psychosocial intervention) or passive (no‐contact) control condition. Interventions were provided in small groups over eight two‐hour sessions with a single booster session offered three months following training. In the initial study, participants were assessed post‐training, as well as three and six months after the intervention. The 127 participants with MCI, who completed the 6‐month post‐training assessment, were contacted five years post‐training. Primary outcomes included a 12‐word free recall task, a self‐reported strategy used in everyday life, and the Montreal Cognitive Assessment screening test (MoCA). Participants randomized to cognitive training were compared to those randomized to the control conditions.

Result

Participants with MCI, who were randomized to the cognitive training condition, showed a reduced 5‐year decline on the delayed recall task when compared to participants in the control conditions. Participants randomized to the cognitive training condition also demonstrated superior delayed recall and MoCA performance than those in the control condition, five years post‐training. There were no differences on self‐reported strategy use.

Conclusion

The positive effect of cognitive training was found five years later on measures of delayed memory and global cognitive status in individuals with MCI. This indicates that the use of cognitive training is a valid preventive approach and has potential to delay the onset of dementia in at‐risk individuals.
Modifiable factors associated with cognitive resistance in the Framingham Heart Study
Authors: Hwang Phillip H , Mez Jesse , Farrer Lindsay A , Devine Sherral , Auerbach Sandford H , Qiu Wendy , Liu Chunyu , Au Rhoda
Published: December 2021

Background

Cognitive resistance to Alzheimer’s disease (AD) refers to an individual’s capacity to avoid the appearance of Alzheimer’s dementia syndrome in the context of risk factors on pathologic processes. We sought to identify associations between potential modifiable risk factors for AD and cognitive resistance.

Method

2,318 participants from the Offspring and Omni cohorts in Framingham Heart Study without prevalent dementia and at high risk for AD were selected. High risk for AD was defined as having ≥2 of the following risk factors measured at baseline: (1) age >80 years; (2) diagnosis of cardiovascular disease or coronary heart failure; (3) carrier of ≥1 APOE ε4 allele; (4) plasma Aβ42/40 ≤0.1049 (Perez‐Grijalba et al.; 2019); (5) C‐reactive protein level ≥10 mg/L (Morley and Kushner; 1982); and (6) female sex. Cognitively resistant individuals were defined as those at high risk for AD that did not progress to a clinical diagnosis of dementia/AD. Standardized research criteria were used to ascertain all‐cause dementia and AD. Potential modifiable risk factors for AD measured at baseline included diabetes, hypertension, obesity, depression, smoking, and education. Logistic regression was used to examine associations between these factors and cognitive resistance to AD.

Result

Over an average period of 36 years, absence of diabetes (OR = 3.63; 95% CI = 2.37 – 5.55; p <0.001) and absence of hypertension (OR = 1.60; 95% CI = 1.02 – 2.51; p = 0.038), as well as not smoking (OR = 2.10; 95% CI = 1.41 – 3.13; p <0.001), at baseline were significantly associated with cognitive resistance. Absence of depression, absence of obesity, or high education were not associated with cognitive resistance.

Conclusion

Individuals at high risk for AD who do not have diabetes or hypertension, or do not smoke may be cognitively resistant to AD. These findings support the heart‐brain connection for dementia prevention and healthy cognitive aging.