bluuebunny/crossref_metadata_2025 huggingface dataset:
Pandemic impact in care homes: Care homes perspectives
Authors: Da Silva Miguel Vasconcelos , Khan Zunera , Comber Tara , Aarsland Dag , Testad Ingelin , Ballard Clive
Published: December 2021

Background

Care Homes (CH) are a vital resource in the health and social care system to support elderly people who may be unable to live at home independently. Older adults and carers have been disproportionately affected by coronavirus (COVID‐19). With 410 00 people living in CH, we lack data of how these major changes have impacted CH, and how CH are managing during the pandemic outbreak. We require knowledge, including what policies and procedures CH currently have; how they are mitigating risks; and how current experiences and guidance can improve care of CH residents during the current pandemic and future crises.

Method

CH members of the Care Home Research Network (CHRN) were invited to take part on an online anonymous survey. An email invitation was sent to 225 CH, with surveys completed between August to October 2020. The questionnaire comprised of 49 questions, focusing on CH details, their views of the impact on the CH, staff and residents, and questions exploring strategies, ideas, and guidelines that the CH followed.

Result

Fifty care homes completed the survey. With 60% of the CH having between 10‐40 beds, and 40% between 50 to more than 100 beds. 76% of the respondents felt that their institution had been affected by the pandemic, with 52% having residents dying due to COVID‐19 and 68% had staff absent due to COVID‐19. 94% of respondents felt an increased level of stress in their role due to COVID‐19, with 22% saying that they could not cope with the increase in the workload and 52% hiring staff to cope with the workload. 70% of respondents felt that residents were feeling lonelier and 56% that residents were more depressed.

Conclusion

CH have been greatly impacted by the Pandemic, with increased anxieties and stress in staff, they lacked the support and resources needed to better overcome the challenges caused by this Pandemic. Moreover, residents were lonelier and more depressed, and their family members were more anxious/worried, requiring more resources from CH to support residents and family members. CH had to adapt, be innovative, find new working ways and using technology to meet residents and family needs.
Reduction in posterior cortical alpha rhythms during eye opening is more abnormal in patients with dementia due to Lewy bodies than Alzheimer’s disease: An EEG study
Authors: Babiloni Claudio , Noce Giuseppe , Lorenzo Ivan , Ferri Raffaele , Lizio Roberta , Soricelli Andrea , Nobili Flavio Mariano , Buttinelli Carla , Giubilei Franco , Fuhr Peter , Gschwandtner Ute , Ransmayr Gerhard , Marizzoni Moira , D'Antonio Fabrizia , de Lena Carlo , Yener Gorsev , Emek‐Savas Derya Durusu , Stocchi Fabrizio , Frisoni Giovanni B , De Pandis Maria Francesca , Del Percio Claudio , Lopez Susanna
Published: December 2021

Background

Alzheimer’s disease (AD) is the first‐most common neurodegenerative disorder due to an abnormal accumulation of amyloid and tau proteins in the brain and explains about 60‐70% of 50 million of patients with dementia worldwide (WHO report, www.who.int). Disease with Lewy Bodies (DLB) is emerging as another important cause of dementia with visual hallucinations, cognitive fluctuations, or REM sleep behavior disorder in the pathological aging. Notably, DLB patients may show not only distinctive post‐mortem intra‐neuronal Lewy bodies but also abnormal accumulation of amyloid and proteins in the brain, raising in‐vivo diagnostic issues (Kantarci et al., 2020). Furthermore, resting state eyes‐closed electroencephalographic (rsEEG) alpha (8‐10 Hz) rhythms in posterior cortical sources showed differences between AD and DLB patients with dementia (Babiloni et al., 2017). Here we tested the hypothesis that cortical sources of rsEEG alpha rhythms during eyes opening may be more abnormal in DLB than AD patients with dementia.

Methods

Clinical and rsEEG rhythms in demographic‐ and age‐matched AD (N = 30), DLB (N = 28), and healthy cognitively unimpaired (Nold, N = 30) persons were available from an international archive. Pathological groups were matched as cognitive status (i.e., dementia grade). Individual alpha frequency peak was used to determine the alpha frequency band on personal basis. The eLORETA freeware estimated rsEEG alpha cortical sources. “Reactivity” to eyes opening was computed computing the percentage of the reduction in the rsEEG alpha (eLORETA) source activity during eyes open over closed condition in posterior (i.e., central, parietal, and occipital) cortical regions of interest.

Results

As compared to the Nold subjects, the patients with dementia due to DLB and AD showed lower “reactivity” to eyes opening in posterior cortical regions (p < 0.05 corrected), this poor “reactivity” being significantly more evident in the former than the latter (Figure 1).

Conclusions

These novel results suggest that neurophysiological oscillatory mechanisms regulating cortical arousal in the visual system during external visual stimuli are more abnormal in DLB than AD patients with dementia, possibly concurring to visual misperceptions and hallucinations reported in DLB patients. References: 1) Babiloni C, et al. Neurobiol Aging. 2017 Jul;55:143‐158. 2) Kantarci K, et al. Neurology. 2020 Jan 21;94(3):e282‐e291.
Anti‐herpetic drugs: A potential way to prevent Alzheimer’s disease?
Authors: Linard Morgane , Bezin Julien , Hucteau Emilie , Joly Pierre , Letenneur Luc , Garrigue Isabelle , Dartigues Jean‐François , Pariente Antoine , Helmer Catherine
Published: December 2021

Background

Considering the potential implication of Herpes viruses in the development of dementia, anti‐herpetic drugs (AHD) may represent a new means of prevention.

Method

Using a medico‐administrative database, we assessed the association between the intake of systemic AHD and the incidence of i) dementia, ii) Alzheimer’s disease (AD) and iii) vascular dementia (VaD) among 68 291 participants over 65 followed between 2009 and 2017. Cox models using systemic AHD as time‐dependent variable were adjusted for age, sex, being beneficiary of a complementary health insurance scheme for low‐income people, the presence of several co‐morbidities (hypertension, diabetes, hypercholesterolemia, stroke, heart diseases), the intake of anti‐inflammatory drugs, the number of consultations, and the number of different medications the year before inclusion.

Result

9.7% of the participants (n=6642) had at least one intake of systemic AHD and 8883 incident dementia were identified. The intake of at least one systemic AHD was significantly associated to a decreased risk of AD (aHR 0.85 95% confidence interval [0.75‐0.96], p=0.009) and, to a lesser extent regarding p‐values, to both dementia any cause (aHR 0.90 [0.82‐0.99], p=0.03) and VaD (aHR 0.80 [0.65‐0.995], p=0.045). As the percentage of participants with a regular intake was very low (among those with at least one intake of systemic AHD, the median number of deliveries per year of follow‐up was 0.12), the efficacy of regular intake of AHD could not be evaluated.

Conclusion

Taking at least one systemic AHD during follow‐up was significantly associated to a risk reduced by 15% of developing AD. Despite the low percentage of participants with a regular intake during the follow‐up, this association may reflect a protective impact of systemic AHD on the prevention of dementia in particular considering the possibility of more regular treatment in the period preceding the inclusion. It also highlights the limitations of medico‐administrative databases to assess the efficacy of a regular intake of systemic AHD given their current use in clinical practice. Thus, given the growing body of evidence supporting the infectious hypothesis, preventive clinical trials with prolonged treatment by systemic AHD are urgently needed.
Cardiovascular and dementia risk scores and their association with dementia‐related biomarkers in a memory clinic population
Authors: Rosenberg Anna , Solomon Alina , Hagman Göran , Wiggenraad Fleur , Kivipelto Miia
Published: December 2021

Background

Risk scores for dementia and cardiovascular disease (CVD) predict dementia development, but their link to underlying brain pathology remains unclear. This study explored the cross‐sectional associations between well‐validated CVD and dementia risk scores and dementia‐related cerebrospinal fluid (CSF) and imaging markers in memory clinic patients without dementia,

Method

The study population consisted of 207 patients with subjective cognitive impairment or mild cognitive impairment from the Karolinska University Hospital, Theme Aging, Memory Clinic, who had CSF (Aβ42, phosphorylated tau, total tau, neurofilament light chain NfL), visual MRI ratings (medial temporal lobe atrophy MTA, Fazekas for white matter lesions WML), and available clinical data to calculate risk scores. CVD risk score (FINRISK) was calculated for all patients; data for the CAIDE Dementia Risk Score (with and without APOE) were available for a subsample (N=88). The associations between risk scores and biomarkers were analyzed with linear regression (zero‐skewness log‐transformed CSF biomarkers as dependent variables) and ordinal regression (MTA and WML ratings as dependent variables). Risk scores were categorized into 3 similar‐sized groups (lower‐, intermediate‐, and higher‐risk groups; lower‐risk group used as reference),

Result

Higher FINRISK score and CAIDE score (with APOE) were associated with lower levels of CSF Aβ42 (coefficients in the higher‐risk groups ‐0.05, p=0.02 for FINRISK and ‐0.08, p=0.04 for CAIDE). Higher CAIDE score (with APOE) was also associated with a lower CSF Aβ42/p‐tau ratio (coefficient ‐0.03, p=0.03 in the higher‐risk group). With respect to neuronal injury markers, a higher risk of CVD and dementia was associated with higher CSF NfL levels (coefficients in the higher‐risk groups 0.58, p<0.001 for FINRISK; 0.38, p=0.001 for CAIDE; 0.34, p=0.005 for CAIDE with APOE). Furthermore, higher‐risk patients had more pronounced MTA (OR 2.3, 95% CI 1.2–4.5 for FINRISK; OR 3.0, 95% CI 1.2–7.4 for CAIDE), and WML (OR 2.4, 95% CI 1.2–4.5 for FINRISK),

Conclusion

Having a higher risk of CVD or dementia was associated with several dementia‐related CSF and imaging markers. Follow‐up studies are needed to explore the utility of different risk scores in assessing risk of cognitive decline and disease progression in memory clinic patients.
Approaches to engage an aging cohort in rural India during the COVID‐19 crisis and the psychological impact of COVID‐19 in this cohort
Authors: Sundarakumar Jonas S , M L Abhishek , Hameed Shafeeq K Shahul , Dilip Babu , Kumar B R Vinay , Deepak Shylashree , Ravindranath Vijayalakshmi
Published: December 2021

Background

The COVID‐19 crisis brought most cohort studies around the world to a standstill. India, which had implemented one of the strictest nation‐wide lockdowns in the world, was no exception. Owing to this, recruitments and assessments in our aging cohort in rural India, namely, Srinivaspura Aging Neurosenescence and COGnition (SANSCOG), had to be abruptly suspended.

Method

The SANSCOG study team undertook active measures to keep our subjects engaged remotely during the COVID‐19‐related lockdown period and also, provided useful services telephonically, to address their anxiety and distress. We collaborated with a local digital health service initiative, to offer counselling on awareness about the disease and safety precautions to be adopted. To assess the psychological impact of the pandemic on our cohort, the study team’s clinicians telephonically administered the Geriatric Depression Scale (GDS‐7) and the Generalized Anxiety Disorder (GAD‐7) questionnaire to consenting subjects. These instruments are brief, validated and sensitive instruments to screen for depression and anxiety disorder, respectively. Among subjects who had pre‐COVID GDS scores (obtained from their baseline clinical assessments), the proportion of subjects having pre‐COVID versus post‐COVID depression was compared.

Result

A total of 1890 subjects from the rural (SANSCOG) cohort were contacted during the lockdown period. Our periodic telephone calls to enquire about the subjects’ well‐being as well as our providing of psychological support and medical advice, when necessary, were appreciated by our subjects. Our collaborative initiative to provide awareness about the pandemic was well‐received, as many of our subjects had inadequate awareness about the pandemic. Overall, these strategies resulted in better bonding between our study team and our cohort. On screening for depression and anxiety disorder, 28.4% scored above the threshold score for depressive disorder on GDS‐7, whereas 5.5% scored above the threshold score for anxiety disorder on GAD‐7. We found that the proportion of subjects with depression had quadrupled after the COVID‐19 pandemic (pre‐COVID ‐ 7.74%, post‐COVID ‐ 28.98%).

Conclusion

The above approaches of cohort engagement during times of crisis are deemed valuable by subjects and we envisage that this would improve subject retention. This rural Indian cohort had a severe psychological impact due to the COVID‐19 pandemic.
Adopting the FINGER multimodal intervention methodology to prevent cognitive decline in Southern Europe: The GOIZ ZAINDU pilot study
Authors: Tainta Mikel , Ecay Mirian , Iriondo Ane , Estanga Ainara , Clerigue Montserrat , Saldias Jon , de Arriba Maria , Garcia‐Sebastian Maite , Aurtenetxe Sara , Barandiaran Myriam , Gabilondo Alazne , Mar Javier , Arrospide Arantzazu , Vergara Itziar , Mugica Justo , Mangialasche Francesca , Ngandu Tiia , Kivipelto Miia , Martinez‐Lage Pablo
Published: December 2021

Background

GOIZ ZAINDU (“caring early” in Basque) is a pilot study to adapt FINGER methodology to the Basque Population and evaluate feasibility and adherence to a FINGER‐like multimodal intervention program. Additional exploratory aims included assessment of efficacy on cognition and collection of necessary data to design a large efficacy trial.

Method

GOIZ ZAINDU is a one year, randomized, controlled trial of a multimodal intervention in persons aged 60+ with increased CAIDE score (≥ 6), no dementia, and below‐than‐expected performance in at least one of three cognitive screening tests. Participants were recruited from a previous program on early diagnosis and risk awareness (GOIZ‐ALZHEIMER). Randomization to a Multimodal intervention (MI) or to Regular Health Advice (RHA) was stratified by cognitive status (MCI/normal) and age (>/≤ 75). MI included cardiovascular risk factors control, nutritional counseling, physical activity and cognitive training. Primary outcome was adherence to intervention program. Cognitive outcomes included Neuropsychological Test Battery z scores change. Analyses were carried out by intention to treat.

Result

125 participants were recruited (mean age: 75.64 (6.46); 58% women). MI (n=61) and RHA (n=64) groups were balanced in demographics and cognition (Table 1). 52 (85%) participants from RHA and 56 (88%) from MI group completed the study. 55% of participants had attended all intervention activities; 70% attended more than half of cognitive sessions; and 55% attended more than half of cardiovascular, nutritional and physical activity program sessions Risk of cognitive decline was higher in RHA group compared with MI in executive Function (EF)(p=.019) and Processing Speed (PS) scores (p=.026) (Table 2). 32 (64%) participants In the RHA and 22 (40%) in the MI group declined in EF; 30 persons (61%) in the RHA and 22 (39%) in the MI declined in PS,

Conclusion

The GOIZ‐ZAINDU study has proved that the FINGER methodology is adaptable and feasible in a different socio‐cultural environment. Exploratory efficacy results show lower risk of decline in EF and PS. These results support the design of a large‐scale efficacy FINGER‐like trial in Southern Europe, the GO‐ON study.
Prevalence of neuropsychiatric conditions in two parallel, aging study cohorts from rural and urban India
Authors: Sundarakumar Jonas S. , Abhishek M. L. , Ravindranath Vijayalakshmi
Published: December 2021

Background

Neuropsychiatric conditions occur more frequently among elderly. With rising proportion of elderly in India, the burden due to neuropsychiatric disorders is bound to escalate. Many of these disorders have been associated with dementia, though the relationship is complex.

Method

Prevalence of neuropsychiatric conditions, such as stroke, head injury, depression and early‐life stress were assessed in two parallel, longitudinal, aging cohorts, from rural and urban India, namely, the Srinivaspura Aging Neurosenescence and COGnition (SANSCOG) study and Tata Longitudinal Study of Aging (TLSA), respectively. As part of their baseline clinical assessments, subjects from both cohorts were screened for depression using the self‐rated, Geriatric Depression Scale (GDS) and the clinician‐rated, Hamilton’s Depression Rating Scale (HDRS). Past history of depression and history of early life stressors, such as parental death and parental divorce in childhood were obtained. Self‐reported history of stroke, head injury and risk for vascular dementia using Hatchinski’s Ischemic Index (HIS) were also assessed.

Result

Proportion of subjects diagnosed with depression using GDS was 9.77% in the rural and 9.66% in the urban cohort, whereas corresponding numbers using HDRS were 6.55% and 3.82%, with female preponderance in both cohorts. Proportion of subjects with past history of depression was 4.82% and 5.07% in the rural and urban cohorts, respectively. Early life parental death was more in the rural 10.91%) as compared with the urban cohort (3.66%). History of stroke was reported in 1.25% and 2.31% of the rural and urban cohorts, respectively. There was no significant difference in proportion of subjects with history of head injury between the rural (4.16%) and urban (4.77%) cohorts. In the rural cohort, 0.23% scored above the threshold for vascular dementia on HIS, whereas none of the subjects scored above the threshold in the urban cohort.

Conclusion

GDS is a more sensitive tool than HDRS at screening for depression in elderly. Neuropsychiatric conditions such as history of stroke, head injury and risk for vascular dementia did not show any consistent trend of variation between both the cohorts. Further longitudinal assessments of these neuropsychiatric conditions along with parallel monitoring of cognitive changes will help in identifying their causal relationship with dementia.
Cross‐sectional association between cardiovascular risk score and cognitive performance in middle‐aged UK Biobank participants
Authors: Li Peng , Zheng Xi , Ulsa Ma Cherrysse , Yang Hui‐Wen , Gao Lei , Hu Kun
Published: December 2021

Background

Cardiovascular diseases (CVD) have been linked with faster cognitive decline and incident dementia. The actual risk factors for CVD also tie to these adverse cognitive consequences in elderly adults. The cardiovascular risk score (CRS) provides direct estimation of total cardiovascular risk that suits well to the constraints of primary prevention. Further data especially in larger populations are required to examine whether CRS is also associated with cognitive performance in middle age.

Methods

We evaluated data from 420,381 participants [aged 37‐73 (mean: 55.9; SD: 8.1) years old; female: 234,464 (55.8%)] in the UK Biobank who were free from dementia and circulatory system diseases at enrollment. Four neurocognitive tests were administered to assess cognition in different domains, i.e., information processing speed (reaction time test, RT), visual episodic memory (pairs matching test, pairs), reasoning (fluid intelligence test, FI), and prospective memory (PM). Longer RT, making more errors during pairs test, lower FI, or making incorrect first choice during PM indicates poorer cognitive performance. To estimate CRS, we applied the 10‐year risk of fatal CVD estimation—the SCORE system—that is based on age, sex, systolic blood pressure, total cholesterol level, and current smoking status. Linear regression models (or logistic regression for PM) examined the associations of CRS with each cognitive outcome, with adjustment for ethnicity, college, social‐economic status, mental and behavioral disorders, diseases of the nervous system, and number of treatments/medications. Sensitivity analyses were done 10 times with randomly chosen subsets of 1/10 participants.

Results

The cohort had a median 10‐year risk of 2.51% (inter‐quantile range: 1.02%‐4.84%; range: 0.08%‐74.3%) in developing fatal CVD. Increased CRS was associated with worse cognitive performance. Specifically, compared with those with CRS<5%, participants with CRS≥5%(higher CVD risk) took 1 ms longer in RT, made 1 more mistake in pairs test, had lower FI score by 0.27, and had 31.4% lower chance of making the correct choice during PM (all p’s<1E‐93). These observations were consistent across 10 sensitivity analyses.

Conclusion

Increased cardiovascular risk during middle life is associated with poorer cognitive performance. Further studies are required to examine whether cardiovascular risk predicts future cognitive decline or dementia.
Monthly computerized at‐home assessments to detect cognitive change in preclinical Alzheimer’s disease
Authors: Jutten Roos J. , Amariglio Rebecca E. , Properzi Michael J , Buckley Rachel F. , Maruff Paul T , Stark Craig E. , Yassa Michael A. , Johnson Keith A. , Sperling Reisa A. , Rentz Dorene M. , Papp Kate V.
Published: December 2021

Background

Alongside the increased focus on detecting Alzheimer’s disease (AD) pathology in the preclinical stage, there is a need to more rapidly track AD‐related cognitive changes that may emerge during this stage. Computerized cognitive testing has the potential to achieve this by enabling more frequent, remote, unsupervised assessments. Here, we aimed to investigate whether monthly at‐home assessments of a modified version of the Behavioural Pattern Separation Task‐Object Version (BPSO) could detect cognitive change in cognitively unimpaired (CU) individuals with and without abnormal AD biomarkers.

Method

N=110 CU participants (age=77.1±4.9, 61% female, MMSE 29±1.3) from the Harvard Aging Brain Study completed the BPSO monthly at‐home on an iPad as part of the Cogstate C3 battery for up to one year (6.3±3.9 months follow‐up). All participants underwent PIB‐PET imaging (1.25±1.05 years before at‐home baseline) and a subset (n=82) underwent Flortaucipir PET (0.56±0.4 years before at‐home baseline). Primary outcome of the BPSO is a metric reflecting the ability to correctly discriminate between stimuli that are similar but not identical to previously learned targets (score range 0‐1, higher scores reflecting better performance). Linear mixed models were used to characterize BPSO performance over months (including both linear and quadratic time terms to investigate nonlinear change), and to examine associations with amyloid (dichotomous) and medial‐temporal tau deposition (continuous) while adjusting for age, sex, education and their interactions with time.

Result

Overall, individuals’ BPSO performance improved over months, as shown by a significant quadratic effect of time (β=‐.002,p<.001) with a plateauing learning curve (Figure 1). On average, amyloid‐positive individuals (n=29) showed slightly worse BPSO performance (β=‐.06,p=.03) than amyloid‐negative individuals, but similar trajectories over time. However, the baseline amyloid effect was attenuated when limiting the sample to those with both amyloid and tau imaging. Less improvement over the year was associated with greater tau burden in the entorhinal cortex (Time*tau β=‐0.02,p=.019) (Figure 2).

Conclusion

We show that subtle alterations in pattern separation performance over repeated exposure in CU individuals are associated with tau deposition in the medial‐temporal lobe. This implies that unsupervised computerized testing using monthly learning paradigms may be an efficient way to early detect cognitive change associated with preclinical AD.
Cortical microinfarcts along the Alzheimer's disease continuum in adults with Down syndrome
Authors: Aranha Mateus Rozalem , Bejanin Alexandre , Montal Victor , Pegueroles Jordi , Carmona‐Iragui Maria , Videla Laura , Benejam Bessy , Valldeneu Sílvia , Barroeta Isabel , Altuna Miren , Fernandez Susana , Garzón Diana , Padilla Concepción , Iulita M. Florencia , Alcolea Daniel , González‐Ortiz Sofía , Blesa Rafael , Lleó Alberto , Fortea Juan
Published: December 2021

Background

Cortical microinfarcts (CMI) are emerging biomarkers of vascular damage that are visually detectable with 3T‐MRI, associated with cognitive decline, and more frequent in AD patients. However, no study assessed CMI in Down syndrome (DS), a genetically determined form of AD. Therefore, we aimed to quantify CMI in a population‐based cohort of adults with DS and assess the relationship with age, sex, clinical status, and APOE genotype.

Method

Cross‐sectional, proof‐of‐principle study. We selected 31 adults with DS from the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) cohort with available 3T‐MR (8 asymptomatic, 11 prodromal AD, and 12 AD dementia individuals; target sample size: 200 DABNI subjects). An expert neuroradiologist blind to clinical diagnosis, age, and APOE status visually analyzed the 3T‐MRI images following previously validated protocol (Figure 1) to detect and manually segment CMI. First, we compared the presence and volume of CMI in the different clinical groups along the AD continuum, in APOEε4 carriers vs. non‐carriers, and in males vs. females using Chi‐square, Mann‐Whitney, or Kruskal‐Wallis tests when appropriate. Then, we assessed the association between the volume of CMI and age using Spearman's correlation test.

Result

CMI were detected in 68% of adults with DS. The frequency of CMI was nominally higher in the prodromal and demented (73% and 75%, respectively) compared to the asymptomatic group (50%, p=0.46) and in males (70%) than females (64%, p=0.72), and significantly higher in APOEε4 carriers (100%) than non‐carriers (58%, p=0.05). The volume of CMI was nominally higher in prodromal and AD dementia patients (16.7 and 12.3mm3, respectively) than in asymptomatic subjects (2.6mm3, p=0.46), in males (12.3 mm3) than in females (7.9mm3, p=0.32), and in APOEε4 carriers (14.9mm3) compared to non‐carriers (7.9mm3, p=0.11) (Tables 1, 2 and 3). No correlations between age and CMI were observed (p=0.37, rSpearman= ‐0.17) (Figure 2).

Conclusion

CMI are detectable using 3T‐MRI in adults with DS and are more frequent than in the general population (6% in non‐demented elderly and 32% in AD dementia patients). They are more prevalent in APOEε4 carriers and might increase along the AD continuum and be more frequent in males.
Ethnicity influences risk of dementia in the UK Biobank
Authors: Bonnechère Bruno , Liu Jun , Thomson Alexander , Amin Najaf , Van Duijn Cornelia M
Published: December 2021

Background

The number of people with dementia is increasing globally and it is expected that low and mid‐income and minorities in high‐income countries will be more severely affected in the next decades. Yet most of the research of dementia has focused on patients of European descent. Findings of US based studies suggest differences in risk across ethnic groups but data are largely lacking with Europe. The aim of this study is to compare the risk and risk factors of dementia across ethnicities in UK.

Method

We analyzed the results of the UK Biobanks (UKB), with participants aged more than 55 year to assess prospectively the risk of dementia according to the ethnicities. The data of all‐cause dementia was obtained from the hospital inpatiant records available. All the previously identified genetic, medical, lifestyle and environmental risk factors were studied using Cox‐regression, adjusting for age, sex and other putative confounders. 278,376 participants were included in the final analysis, among whom the vast majority are identified as White (97.79%) by UKB, followed by Asian (1.36%), and Black (0.84%). The mean duration of the follow‐up was 11.2 years with 3,111,197 person‐years in total.

Result

5,029 participants developed dementia during the follow‐up: the incidence of dementia is 160 cases/100,000 person‐years in White, 178 cases/100,000 person‐years in Asian, and 274/100,000 person‐years in Black. After adjusting for risk factors, participants identified as Black in the UKB are at increased risk of developing dementia (HR = 1.63 [1.22 – 2.19], p < .002), but not (HR = 1.14 [0.85 – 1.54], p = .205). This increased risk may be due to the higher proportion of APOE44 carriers in UKB Blacks (5.4%) compared to Whites (2.3%) and Asians (1.1%) but also more frequent comorbidity including head trauma and hypertension. Despite the higher prevalence of diabetes and related factors in those of Asian descent, the risk of dementia was not significantly increased.

Conclusion

In contrast to earlier US based findings, our study shows an increased risk of dementia in those of African descent living in the UK, which is partly explained by genetic risk factors and comorbidity.
A high‐performance biomarker panel for Alzheimer’s disease screening and staging identified by large‐scale plasma proteomic profiling
Authors: Jiang Yuanbing , Zhou Xiaopu , Ip Fanny C.F. , Chan Philip , Chen Yu , Lai Nicole Chit Hang , Cheung Kit , Lo Ronnie M.N. , Tong Estella Pui‐Sze , Wong Bonnie W.Y. , Chan Andrew L.T. , Mok Vincent C.T. , Kwok Timothy C.Y. , Mok Kin Y. , Hardy John , Zetterberg Henrik , Fu Amy K.Y. , Ip Nancy Y.
Published: December 2021

Background

Blood proteins are emerging candidate biomarkers for Alzheimer’s disease (AD). A comprehensive investigation of the AD blood proteome will help identify additional biomarkers to delineate the disease’s pathways and define specific AD stages.

Method

We quantified 1,160 plasma proteins in a Hong Kong Chinese cohort (n = 106 AD patients, n = 74 healthy controls) by high‐throughput proximity extension assay to identify AD‐associated plasma proteins.

Result

Plasma proteins involved in diverse biological processes were found to be dysregulated in AD. A subset of plasma proteins was selected to represent the AD plasma protein profile, which formed the basis of a scoring system that can accurately classify AD and associated endophenotypes. In addition, we showed that certain plasma proteins and biological processes exhibit stage‐specific dysregulation in AD, thus adding biological annotations to AD stages.

Conclusion

This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high‐performance, blood‐based test for clinical AD screening and staging.
Neural signatures of meaning in life dimensions and its contribution to self‐perceived cognition in middle‐aged individuals
Authors: Abellaneda‐Pérez Kilian , Cattaneo Gabriele , Cabello‐Toscano María R , Vaqué‐Alcázar Lídia , Solana Javier , Mulet‐Pons Lídia , Bargalló Núria , Tormos‐Muñoz Josep M , Pascual‐Leone Alvaro , Bartrés‐Faz David
Published: December 2021

Background

Meaning in life (MiL) encompasses purpose in life (PiL), engagement with life (EwL), and sense of coherence (SoC) dimensions. MiL estimates have been associated with self‐reported cognitive status amongst middle‐aged individuals (Bartrés‐Faz et al., Alzheimers Res Ther. 2018;10(1):47). Later in life, MiL factors have been related to reduced cognitive decline and delayed onset of dementia in Alzheimer’s disease (AD; Boyle et al., Arch Gen Psychiatry. 2010;67(3):304‐310). However, how MiL dimensions are associated with brain networks’ expression and if these functional systems could mediate the influence of MiL on self‐perceived cognition remains unknown.

Methods

Demographic, cognitive, and neuroimaging data was obtained from 585 middle‐aged adults (mean age 54.26 ± 7.1; 289 women) from the Barcelona Brain Health Initiative cohort (https://bbhi.cat/en/). Linear regression analyses were used to investigate the associations between MiL and its three dimensions [motivational (PiL), emotional (EwL), and cognitive (SoC)] and the strength of functional connectivity within the main brain resting‐state networks (RSNs; Shirer et al. Cereb Cortex. 2012;22(1):158‐165). Further analyses were computed to explore to which extent RSNs mediate the effect of MiL and its dimensions on self‐reported cognition, derived from the PROMIS® Cognitive Abilities and Concerns scale. Data was adjusted for age, personality, cognitive reserve, and affective status. Correction for multiple comparisons was applied.

Results

MiL estimates and its SoC factor, but not EwL and PiL, were correlated with RSNs. Specifically, significant associations for SoC emerged for those RSNs linked to higher‐order cognitive processing, such as the default‐mode, the salience and the left and right executive‐control networks. However, associations with sensorimotor systems were not significant. The links between SoC and self‐perceived cognitive function were mediated by the salience and the left executive‐control circuits (Fig. 1).

Conclusion

The observed associations between SoC and the functional systems subtending cognitive processing, but not sensorimotor functions, may be related to previous observations indicating that MiL‐related factors are associated to greater than expected cognitive function for a given level of AD pathological load (Boyle et al., Arch Gen Psychiatry. 2012;69(5):499‐505), therefore promoting brain resilience in advanced age.
Is depression associated with cognitive decline in a diverse cohort of the oldest‐old? Findings from the LifeAfter90 Study
Authors: Whitmer Rachel A. , Gilsanz Paola , Mungas Dan M. , George Kristen M. , DeCarli Charles S. , Kawas Claudia H. , Vieira Katharine E. , Glymour M. Maria , Corrada Maria M.
Published: December 2021

Background

Depression impacts 50% of the elderly population and is a risk factor for dementia but its prevalence and role in cognitive decline in Non‐Whites and the oldest‐old is unclear.

Method

LifeAfter90 is a racially/ethnically diverse cohort of individuals aged 90+ that launched in 2018 with the aim of characterizing cognitive and brain aging after the 9th decade of life. Participants are members of an integrated healthcare delivery system without a dementia diagnosis in their medical record at recruitment. Depression at baseline was evaluated with the Global Depression Scale (GDS) and defined as GDS>4. Cognitive testing every 6 months uses the Spanish and English Neuropsychological Assessment Scales (SENAS), to assess cognitive domains of episodic memory, semantic memory, and executive function. Linear mixed models with random intercepts, evaluated the baseline and longitudinal association of depression with each SENAS domain. The models used years since baseline as the time variable, and adjusted for baseline age, sex, race/ethnicity, education, and practice effects. An interaction term (depression*time) tested for differences in decline in cognitive domains by baseline depression status.

Result

Of 655 participants 32% are White, 22% Asian, 22% Black, 15% Latino, and 8% Other/Multiracial. 35% had <high school education, 38% were male, and mean age was 93 years. At baseline, 32% were classified as having depression with the highest prevalence among Latinos and those with <high school education (Table 1). The average follow‐up was 0.9 years (range: 0‐1.9). Depression was associated with poorer semantic memory (ß=‐0.17) and executive function (ß=‐0.18) but not with episodic memory (Table 2). Semantic memory (ß=‐0.28) and executive function (ß=‐0.11) decreased over time, however episodic memory did not. The semantic memory and executive function decline did not differ by depression (Figure 1 & Table 2).

Conclusion

Depression impacts one third of this ethnically diverse cohort of oldest‐old individuals and ais more prevalent in Latino participants. While depression is associated with poorer baseline semantic memory and executive function; it is not associated with episodic memory, nor is it associated with greater cognitive decline. These results suggest that while depression may impact cognitive performance it may not impact cognitive change in those aged 90+.
Towards optimizing the measurement of self‐perceived cognitive functioning: Examination of harmonized subjective cognitive items
Authors: Rabin Laura , Tommet Douglas , Jones Richard N , Crane Paul K. , Sikkes Sietske A.M. ,   SCD‐I Working Group, SCD‐PIA
Published: December 2021

Background

For the item analysis project of the Subjective Cognitive Decline Initiative (SCD‐I) Working Group, we have pooled item level data from North American, European, and Australian cognitive aging studies. As a step toward developing a questionnaire that can be used across settings and studies, we examined similarly worded groups of items and compared their psychometric quality.

Method

Item‐level subjective cognitive data were combined from 21 studies (>18,000 participants). Unidimensional models consistent with item response theory captured a general subjective cognition factor using ADNI as the reference sample. Other studies were calibrated by using parameter constraints on common items. We characterized the measurement properties of 648 items from 35 measures utilized in the contributing studies. Next, we identified 20 groups of items (median items per group=6) with overlapping content from our previous study (Rabin et al., 2015), and plotted their item information curves, reflecting the items’ ability to discriminate between trait scores at different levels of the subjective cognition factor score. We then considered items with the highest peak information across groupings and identified commonalities in key features such as terminology of item stems, temporal referents, and response options.

Result

We present instrument characteristics (Table 1) and item information curves for 6 groupings (Figure 1). For items with the greatest information, we observed trends for the following features: clarity and directness of language of stem, utilization of current as opposed to other time referents, assessment of ability/level of difficulty rather than change over time or frequency of problem (Table 2).

Conclusion

We identified key linguistic/structural features of subjective cognitive functioning items with the greatest contributions to measurement precision. We next plan to analyze all item groupings in our test bank to facilitate construction of a measure with high quality items from cognitive domains of interest (e.g., memory, language, executive functioning). Ultimately, we hope to derive a subjective cognitive screening tool that enables reliable identification of subtle cognitive changes in clinically normal individuals.
A remote smartphone cognitive testing battery for frontotemporal dementia: Completion rate, reliability, and validity
Authors: Staffaroni Adam M. , Taylor Jack C , Clark Annie L , Heuer Hilary W. , Forsberg Leah K. , Bahl Riley , Manoochehri Masood , Vento Stephanie , Bajorek Lynn P. , Ong Elise , You Michelle , Boeve Bradley F. , Kramer Joel H , Rosen Howard J. , Boxer Adam L.
Published: December 2021

Background

In preparation for treatment trials in frontotemporal dementia (FTD), sensitive assessments to detect early clinical deficits and track longitudinal changes are needed. Remote digital data collection using smartphones may improve sensitivity to detect and follow abnormalities by allowing novel methods of data capture and more frequent assessments. Furthermore, remote evaluations can reduce patient and staff burden. Despite these benefits, little is known about the reliability and validity of self‐administered cognitive testing completed on smartphones.

Method

We investigated self‐administered smartphone cognitive tests from the ALLFTD Mobile App in a mixed sample of 45 participants, including 10 functionally intact older adults, 24 participants from families harboring pathogenic FTD mutations (asymptomatic n=14; mildly symptomatic n=10;), and 11 symptomatic FTD‐spectrum participants. A subset (n=15) was missing CDR®+NACC‐FTLD data but consensus diagnoses were available. Participants were asked to complete five tests that were repeated three times over eight days. Tests included versions of N‐back, Stroop, Flanker, and Go/No‐Go paradigms, and an adaptive spatial working memory test. Reliability was assessed using split‐half reliability (first testing session, 100 simulations) and intraclass correlations (ICC) across the three testing sessions. Linear models were fitted to evaluate the association of test performance with age and disease severity (CDR®+NACC‐FTLD Global and Box Scores), covarying for sex and education level. Models evaluating age associations excluded symptomatic participants.

Result

Participants completed 72.4% of available instruments. Split‐half reliability (range: 0.76 to 0.97) and ICCs (0.70 to 0.92) suggested adequate‐to‐excellent internal consistency and test‐retest reliability. Across the five tests, negative associations were observed with CDR®+NACC‐FTLD Box Scores (ßs = ‐0.24 to ‐0.77), and in clinically asymptomatic individuals, negative associations were observed with age (ßs = ‐0.43 to ‐0.88). Performance on all measures was worse in symptomatic participants compared to asymptomatic (p‐values<.05). Mildly symptomatic cases (CDR®+NACC‐FTLD=0.5) performed worse on Stroop, Flanker, and spatial working memory than asymptomatic participants (p‐values<.03). Flanker and Stroop tasks consistently showed the strongest reliability and validity findings.

Conclusion

Smartphone adaptations of common neuropsychological tests produced promising preliminary results. Strong associations with disease severity and age suggest these metrics may be valid for detecting clinically relevant cognitive changes, even in mildly symptomatic FTD.
Association of air quality improvement with slower decline of cognitive function in older women
Authors: Younan Diana , Wang Xinhui , Millstein Joshua , Petkus Andrew J , Beavers Daniel P , Espeland Mark A , Chui Helena C , Resnick Susan M , Gatz Margaret , Kaufman Joel D , Wellenius Gregory , Whitsel Eric A , Manson JoAnn E , Rapp Stephen R , Chen Jiu‐Chiuan
Published: December 2021

Background

Late‐life exposure to ambient air pollution is a modifiable risk factor for dementia, but epidemiological studies have shown inconsistent evidence for cognitive decline. Improved air quality (AQ) is associated with decreased mortality and improved respiratory health, but no studies have examined the association with cognitive function.

Methods

Participants included 2,232 U.S. community‐dwelling older women (aged 74‐92) from the Women’s Health Initiative Memory Study‐Epidemiology of Cognitive Health Outcomes (WHIMS‐ECHO) without dementia at enrollment. Measures of annual (2008‐18) cognitive function included general cognitive status (assessed by the Telephone Interview for Cognitive Status‐modified, TICSm) and episodic memory (assessed by the telephone‐based California Verbal Learning Test, CVLT). Regionalized universal kriging models were used to estimate annual exposures (1996‐2012) to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) at residential locations, which were averaged over the 3‐year periods immediately preceding (recent exposure) and 10 years prior to (remote exposure) WHIMS‐ECHO enrollment. Individual‐level improvements in AQ were calculated as the reduction from remote to recent exposures. We used linear mixed effect models to examine the associations between improved AQ and the rates of cognitive decline in TICSm and CVLT trajectories, adjusting for sociodemographic, lifestyle, and clinical characteristics.

Results

AQ improved significantly for both PM2.5 and NO2 over the 10 years before enrollment. During a median of 6.2 (inter‐quartile‐range [IQR]=5.0) years of follow‐up, general cognitive status (βTICSm=‐0.42/year, 95% CI: ‐0.44, ‐0.40) and episodic memory (βCVLT=‐0.59/year, 95% CI: ‐0.64, ‐0.54) significantly declined. Greater AQ improvement was associated with slower decline in TICSm (βPM2.5=0.026/year per IQR=1.79 µg/m3, 95% CI: 0.001, 0.05; βNO2=0.034/year per IQR=3.92 ppb, 95% CI: 0.01, 0.06) and CVLT (βPM2.5=0.070/year per IQR=1.79 µg/m3, 95% CI: 0.02, 0.12; βNO2=0.060/year per IQR=3.97 ppb, 95% CI: 0.005, 0.12). The respective associations with TICSm and CVLT were equivalent to the slower declines found in women 0.9‐1.2 and 1.4‐1.6 years younger, and did not significantly differ by age, region, education, ApoE e4 genotypes, or cardiovascular risk factors. The benefits were attenuated after excluding incident dementia cases but remained after excluding prevalent or incident stroke cases.

Conclusions

Long‐term improvement in AQ in late‐life was associated with slower cognitive declines in older women.
The Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog): Validation of Slovenian version for detecting mild cognitive impairment or Alzheimer's dementia
Authors: Ulbl Janina , Rakusa Martin
Published: December 2021

Background

With the increasing number of elderly, it is necessary to have a brief screening tool for detecting people with cognitive impairment. Our study aimed to standardise and validate the Slovenian version of ADAS‐Cog for a cognitive screening of people with MCI or AD.

Method

We included 26 people with MCI, 20 with AD, and 45 healthy controls. All participants completed the Slovenian version of ADAS‐Cog. We calculated the mean age, years of education, and ADAS‐Cog score for each group and compared them ANOVA. In the end, we draw the Receiver operator curve (ROC), calculated sensitivity, specificity, and likelihood ratio.

Result

People with AD had the highest total ADAS‐Cog score, followed by MCI and healthy controls (26 SD 12 vs 19 SD 7 vs 8 SD 2 points, p<0.001). There were no statistically significant differences between groups in age or years of education.

The area under the ROC for MCI was 0.97 (CI 0.9 to 1; p<0.0001) and for the AD was 0.98 (CI 0.95 to 1; p<0.0001). Optimal the cut‐off for the ADAS‐Cog for MCI was 11/12 points. Sensitivity was 92% (CI 76% to 99%), specificity 96% (CI 85% to 99%), and likelihood ratio 21. The optimal cut‐off for AD was 14/15 points. Sensitivity was 95% (CI 76% to 100%), specificity 100% (CI 92% to 100%).

Conclusion

The optimal cut‐off score for Slovenian population is 11/12 points for MCI and 14/15 points for people with AD dementia. We may conclude that ADAS‐Cog is a reliable screening tool in our population.