bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of pathological hallmarks and association with post‐mortem MRI cortical thickness in typical and atypical Alzheimer’s disease
Authors: Jonkman Laura E. , Boon Baayla D.C. , Frigerio Irene , Steenwijk Martijn D. , Preziosa Paolo , Hoozemans Jeroen J.M. , Bouwman Femke , Rozemuller Annemieke J.M. , Van de Berg Wilma D.J.
Published: December 2020

Background

Alzheimer’s disease (AD) may present with typical amnestic symptoms (70%) as well as atypical non‐amnestic symptoms such as spatial disorientation, aphasia, or behavioural change. This heterogeneity in clinical symptoms is reflected by pathology and neuroimaging, showing different patterns of protein aggregation, inflammation and atrophy. In this study we aimed to assess the within‐subject regional pathological abnormalities and association with MRI cortical atrophy in clinical phenotypes, using a post‐mortem MRI‐pathology pipeline.

Method

16 clinically confirmed AD donors, eight typical (4F, 73y ± 9) and eight atypical (3F, 63y ± 11), and 11 non‐neurological donors (6F, 70y ± 7) underwent post‐mortem in‐situ 3T MRI. Upon subsequent autopsy, eight cortical regions were selected for paraffin embedding and Aβ, (p‐)tau and CD68 (clone KP1) immunohistochemistry, which was quantitatively analysed as area %‐load with ImageJ. Freesurfer was used on T1 images to calculate regional cortical thickness. Outcome measures were compared across groups using non‐parametric tests. In a linear mixed model we related regional pathology with cortical thickness, adjusting for age and post‐mortem delay.

Result

Across all regions, Aβ, (p‐)tau and CD68 load differed between groups; more pathology in (a)typical AD than controls (all p< 0.001), and more (p‐)tau and CD68 in atypical versus typical AD (p<0.001 and p<0.01). Cortical thickness differed between atypical AD and controls (p<0.001), and between atypical and typical AD (p<0.01).

Within regions, only comparing clinical phenotypes, no difference in Aβ load or cortical thickness was found, but there was more (p‐)tau in the precuneus (p = 0.04) and more CD68 in the middle (p = 0.03) and superior frontal cortex (p = 0.028) in atypical AD.

Across all groups and regions, there was a negative association between cortical thickness and Aβ (p<0.05), (p‐)tau (p<0.001) and CD68 load (p<0.001). Within AD groups, cortical thickness showed a negative association with Aβ for atypical AD, with (p‐)tau for both phenotypes. Within regions, associations with (p‐)tau and CD68 were found for frontal and parietal thickness in (a)typical AD, but none survived Bonferroni correction.

Conclusion

Our results show regional differences in (p‐)tau, CD68 and cortical thickness between typical and atypical AD, indicating different patterns of pathology and influence on MRI cortical thickness between phenotypes.
Suitability of dementia risk scores as surrogate outcomes for lifestyle‐based multidomain prevention trials
Authors: Hoevenaar‐Blom Marieke P , Coley Nicola , van Dalen Jan Willem , van Charante Eric P Moll , Kivipelto Miia , Soininen Hilkka , Andrieu Sandrine , Richard Edo ,   PRODEMOS Consortium, preDIVA Study Group, MAPT/DSA Group, HATICE Consortium
Published: December 2020

Background

Although not designed as such, dementia risk scores, such as the CAIDE or LIBRA, might be useful as surrogate outcome measures for dementia prevention trials conducted from midlife onwards. In the risk scores’ original categorical scoring systems, changes in risk factors are only taken into account when crossing cut‐off values, which may limit responsiveness and ability to detect intervention effects. We hypothesized that scoring systems based on continuous z‐score measures of risk factors may improve the performance of risk scores in this respect.

Method

In three large multidomain dementia prevention trials (MAPT, preDIVA and HATICE) with 1.5‐2 years of follow up, we assessed of the original and z‐score versions of the CAIDE and LIBRA scores: 1) responsiveness and 2) actual and simulated intervention effects.

Result

Across the three trials, 48 to 58% of intervention group participants underwent change on the CAIDE score between baseline and follow‐up. The LIBRA index was more responsive: 61 to 79% of participants changed over time. The z‐score versions registered changes in risk factors that were not detected by the original scores: subjects with no change over time in the original score showed great variability in their change in z‐scores, ranging from as much as ‐1.25 to 1.25 for the CAIDE. Conversely, for very small changes in z‐score, the change in original CAIDE or LIBRA scores was as much as ‐5 to 5 points, indicating multiple small changes in risk factors just across the cut‐off values for the original scoring system. Original scores and z‐scores were equally able to detect modest but significant intervention effects. When simulating very large intervention effects, mean between‐group differences of ‐0.50 points (23% of potential for improvement) could be attained for original CAIDE score and ‐0.52 points for original LIBRA index (15% of potential for improvement). Their z‐score versions could attain a maximum of ‐0.24 standard deviations for CAIDE and ‐0.15 standard deviations for the LIBRA index.

Conclusion

Dementia risk scores as well as their z‐score versions show potential as surrogate outcomes. How changes in risk scores affect long‐term dementia incidence rates remains to be determined.
Genetic markers for brain plasticity
Authors: Brouwer Rachel M. , Klein Marieke , Grasby Katrina L , Schnack Hugo G. , Jahanshad Neda , Teeuw Jalmar , Medland Sarah E. , Franke Barbara , Thompson Paul , Pol Hilleke E. Hulshoff ,   ENIGMA Plasticity Working Group
Published: December 2020

Background

Under the influence of genes and a varying environment, human brain structure changes continuously throughout the lifespan. The quest to identify genetic variants that affect the speed of brain aging is of crucial importance for public health and to guide drug development. As structural brain changes vary considerably across individuals, longitudinal studies are crucial to identify genetic and environmental factors that influence development and aging. Brain changes have been shown to be a heritable phenotype (Brouwer et al., 2017). Yet, we still completely lack information on specific genetic variants that influence brain changes throughout life.

Methods

Through the ENIGMA plasticity working group as part of the ENIGMA consortium (Thompson et al., 2019), we recruited 10,163 subjects [age 4 – 99 year] from 37 cohorts worldwide who had longitudinal structural MRI and whole‐genome genotyping data available in a prospective meta‐analysis design. Longitudinal image processing (Reuter et al., 2012), genomic imputation (Das et al., 2016), quality control and genome‐wide association procedures (Feng et al., 2014)followed a harmonized protocol in each cohort separately. Meta‐analysis and genome‐wide meta‐regressions accounting for age‐dependent effects of genetic variants were performed for global and subcortical structures.

Results

Change rates of global brain measures showed different patterns with age. We identified 5 genome‐wide significant loci and 15 genome‐wide significant genes, associated with longitudinal brain changes, including an age‐dependent effect of Apolipoprotein E (APOE) in the hippocampus and amygdala. Our results suggest a role for metabolic and immune related processes‐shaping brain change throughout our lives.

Conclusion

We discovered novel genetic effects that influence the speed of both development and aging of brain structures. Our findings are consistent with the changing expression of genes during development and aging (Kang et al., 2011). In conclusion, our study implicates a specific genetic background for inter‐individual differences in human brain plasticity throughout life.
Challenges and coping strategies in family‐based dementia care in the Philippines
Authors: Cruz Precy S , Dominguez Jacqueline C
Published: December 2020

Background

The National Dementia Plan in the Philippines has just started. While there are existing pre‐planned strategies on dementia prevention and treatment, long‐term or sustained home‐based care for patients with dementia is limited taking into account that the Philippines is still a developing country that is challenged by inadequate government‐funding/s and resources. Hence, there is a call for the National Dementia Plan to place further consideration on the country’s population characteristics as well as of its culture of care that are cognizant primarily of the value of family care practices in the dementia in local setting.

Purpose

1) To identify the challenges experienced and the coping strategies used by Filipino families as they take care of patients with dementia in their homes. 2) To describe the home environment and surrounding cultural systems in which Filipino families provide with patient with dementia.

Method

Ten family caregivers were interviewed. Data derived were organized into categories and major themes.

Results

The study found that the family caregivers, in spite of the limitations in resources and amidst severity of symptoms, can adapt to the different challenges and situations surrounding the care for patient with dementia at home. Apparently, cultural values inherent in local setting such as close‐family ties and the seeming dictum that Filipino households are bound to take care of their elderlies were likewise found to have an invaluable role in dementia care. Also, being a Christian country adjunct to the situation that most of Filipino families are Catholics, religion and faith were identified as prime coping mechanisms related to dementia‐care.

Recommendations

1) Encourage consistent and sustained involvement of the family in the provision of care for patients with dementia (inclusive primarily of social, financial, and psychological support), 2) Develop and/or refine health‐care policies strengthened and supported by research‐based data on home‐based dementia care germane to local setting.
Association between APOEε4 genotype and cardiovascular risk factors in Mexican elderly adults with amnestic and non‐amnestic mild cognitive impairment
Authors: Mimenza Alberto Jose , Aparacio Itzel Irais , Funes José A. Avila , Navarro Sara Gloria Aguilar
Published: December 2020

Background

The prevalence of mild cognitive impairment (MCI) is 14 to 18%. MCI has been associated with cardiovascular risk factors. Likewise, the APOEε4 genotype is a gene that confers susceptibility to Alzheimer’s disease. However, the association between APOE genotype, cardiovascular risk and MCI in the Mexican population is not clear, probably as a result of genetic heterogeneity.

Method

We included patients from memory clinic (INCMNSZ) from 2017 to 2019, > 70 years. Three groups were studied: controls without cognitive impairment, with amnestic and nonamnestic MCI. Parametric and nonparametric statistics (x2, ANOVA, multivariate logistic regression analysis, Kruskal‐Wallis) were used for the analysis of statistical differences between groups.

Result

131 patients were studied, 67.9% were women, the average age was 73.6 (SD 7.3) and the educational level was 12.62 (SD 4.98). Regarding the APOE genotype, 93 (71%) were e3 / e3, 35 (26.7%) e3 / e4, 3 (2.3%) e4 / e4. Three groups of cognitive function were formed: cognitively healthy controls: 59 (45%), amnestic MCI: 29 (22.1%) and nonamnestic MCI: 42 (32.1%). In the group with nonamnestic MCI, statistically significant differences were found in dyslipidemia 48% (P = 0.014), history of CVD 16.5% (P = 0.033) and anemia 8% (0.034). For the group with amnestic MCI, 44.4% hypothyroidism was found (p = 0.15). The multivariate logistic regression analysis showed that the APOE genotype did not significantly modify the association with cardiovascular risk factors and MCI. A greater effect on motor executive function was found in the group of carriers of the APOEε4 genotype (p = 0.042)

Conclusion

Our study found a low frequency of APOE ε4, compared to African or European populations (Pygmy population, khoisan, waiwai) where the frequency is high (possibly related to race). Previous studies have shown an association between cardiovascular risk and cognitive risk in patients with APOE ε4, however, our study does not show an association between the state of APOE and risk for cognitive impairment, possibly related to variability genetics of the Mexican population, as well as the existence of possible polymorphisms not described in this population. Few studies have shown the association between APOE ε4 polymorphism, hypothyroidism and amnestic DCL.
A family‐centered approach to dementia caregiving: The case of Arab Americans
Authors: Ajrouch Kristine J , Janevic Mary , Antonucci Toni C
Published: December 2020

Background

Research findings increasingly show that the primary caregiver paradigm is not a good fit for many cultures (Gallagher‐Thompson et al., 2000; Dilworth‐Anderson et al., 1999; Aranda & Knight, 1997). In terms of Arab American communities, findings show the need for a family‐centric approach to caring for older adults (Ajrouch, 2017; Ajrouch & Fakhoury, 2013; Sengstock, 1996). The Arab population in Michigan grew 47% between 2000 and 2013, estimated at over 300,000 residents (Arab American Foundation Institute, 2014), and 11% are aged 65+ (American Community Survey, 2013‐2018). We advance a family systems framework by invoking convoys of caregiving (Sherman, Webster & Antonucci, 2013), highlighting that all caregivers, but especially in certain cultures, are surrounded by key others. This paper presents the process by which we developed a culturally congruent Alzheimer’s Disease (AD) caregiver intervention for Arab American families.

Method

Three focus groups were organized with Arab Americans caring for a family member with AD. One focus group was organized with professionals who work with Arab Americans. Focus group discussions were held at a local Arab American social service organization, and gathered data on the role of family in caregiving, Arab American needs, and reactions to proposed intervention formats. Inductive analysis identified and refined study themes applied to modify an existing support program from the Alzheimer’s Association.

Result

Results identified universal (e.g., burnout,) as well as culturally unique themes around the family caregiving experience. Culturally unique themes included “national origins,” which alerts us to ensure examples and scenarios used are familiar, but also introduces need for ensuring and communicating confidentiality; “family dynamics,” which introduces need to build on strengths, while at same time convey importance of accepting help; and “cultural ideals,” which shape how to introduce formal support options. We illustrate how results were applied to modify program delivery and content.

Conclusion

This approach provides direction for addressing cultural needs/preferences within family contexts. Successful modification of an existing intervention includes capturing group ideals, engaging with community partners as equals, and making cultural representations visible. Next steps will involve evaluation of the modified program, program refinement and a final tool kit.
Regional correlates of linguistic error types using the Mini Linguistic State Examination (MLSE)
Authors: Patel Nikil , Barrick Thomas R. , Peterson Katie A. , Ingram Ruth , Garrard Peter
Published: December 2020

Background

Primary progressive aphasia is a clinically and pathologically heterogeneous condition. The currently recognised subsyndromes are non‐fluent, fluent and logopenic variants. The MLSE adopts a novel error‐scoring system to classify the PPA syndromes, and has previously been shown to distinguish the syndromic subtypes based on performance in five linguistic domains: motor speech, phonology, semantics, working memory and syntax. Further validity of this method can be achieved with brain MR correlates specific to the MLSE language domains. For instance, shortfalls in semantics would be expected for correlate with atrophy in bilateral anterior temporal gyrus, and errors in motor speech and syntax with regions in the left inferior frontal gyrus.

Methods

The cohort compromised of 105 participants, 61 patients with a root diagnosis of primary progressive aphasia (PNFA, 20; LPA, 24; SD, 17) and 44 matched controls. The MLSE was administrated on all participants who also had 3T MR imaging. Group level analysis was carried out using voxel‐based morphometry and Statistical Parametric Mapping with a region of interest approach.

Results

We observed a pattern of high sensitivity and specificity for the proposed atrophy patterns (bilateral anterior temporal cortex) associated with semantic errors. Similarly, correlations with atrophy in left inferior frontal and insular regions were observed for deficits in motor speech, phonology and syntax. Regional correlates with working memory deficits were more diffuse.

Conclusions

The results of this study provide evidence that assessment using error types aids classification and differentiation of the profile of PPA patients and conforms with patterns of MR atrophy that would be expected based on previous research.
Social relationships and the rate of cognitive decline among older adults in Lebanon: Differences by gender
Authors: Bakkar Amar Al , Chaaya Monique , Abiad Lilian Ghandour , DeJong Jocelyn , Chaaya Monique
Published: December 2020

Background

Cognitive decline is an increasing public health problem with ageing of populations worldwide. Evidence from developed countries is accumulating on the role of social relationship on cognitive decline. No such studies in the Middle East. The aim of this study was to assess the effect of social network and social engagement on cognitive decline and explore differences by gender among older adults in Lebanon.

Method

Data were derived from the COLDS’ study (Cohort of Older Adults in Lebanon: A Dementia Study). Out of a cohort of 508 older adults, 273 participants did not have cognitive decline at baseline and these constitute the sample of current study. Cognitive decline was estimated using the Arabic version of the IQCODE. The social network dimension consisted of the participant’s marital status and his /her contact with relatives, friends, and neighbors. Social engagement included attending religious meetings, engaging in any community activities, and involvement in any kind of paid work. Simple and multiple logistic regression analyses were performed adjusting for cluster effect. To explore the effect of Gender on the association between exposure variables and cognitive decline, stratification by gender was done at the bivariate and multivariate level. Interaction terms were added to logistic regression models to check for statistical significance of the interaction with gender.

Result

Adjusting for age, gender, educational level, depression, difficulties in performing daily activities, and other social factors, only frequent contact with children or other relatives was significantly associated with lower odds of cognitive decline after 3 years of follow‐up (adjusted OR= 0.37, 95 % CI 0.14‐0.97). No evidence of difference by gender was found.

Conclusion

The findings highlight the importance of support received from children and close relatives particularly in a country like Lebanon where the social life of elderly is centered on the family, while friends and neighbors play a lesser role. Children and close relatives may influence older people’s health by motivating positive healthy behaviors. Future longitudinal studies should explore in a comprehensive framework how social interactions and cognitive status would change throughout the follow‐up period and the dynamics through which they would influence each other.
The effect of virtual reality (VR)‐based intervention program on brain and cognition in older adults with mild cognitive impairment (MCI)
Authors: Thapa Ngeemasara , Park Hyejin , Yang Jakyung , Kim Hansol , Son Haeun , Jang Minwoo , Lee Jihyeon , Park Hyuntae
Published: December 2020

Background

Given the current lack of evidence for intervention and disease‐modifying treatment for Mild cognitive impairment (MCI) and dementia, exploring new interventions is important. VR interventions have increasingly gained popularity in psychotherapy and behavioral therapy, and the potential of VR based interventions to improve cognition are also being explored. However, the evidences regarding its effect on dementia are quite ambiguous. Therefore, we aimed to synthesize the effects of VR interventions for older adults with MCI/ Mild dementia.

Method

Seventy‐five subjects, with mean age 72.5±5.32 years (mean ± standard deviation), participated in this study. The subjects were randomly assigned to either control or VR intervention groups. The intervention group performed series of 4 types of VR based cognitive training program for 6 weeks. Three sessions were held per week and each session lasted for 90 minutes. Cognitive function was assessed with Mini mental state examination (MMSE) test, Trail making test (TMT) A & B, and Digit symbol substitute test. Resting state EEG was measured in eyes open and eyes closed condition for 5 minutes each with 19 channel wireless EEG device. Socio‐demographic characteristics data like education, age, and smoking, and physical function data like short physical performance battery (SPPB), gait speed, were also acquired.

Result

The scores on TMT B improved in intervention group after 6 weeks of VR training compared to control group. The intervention group, in resting state EEG, showed improved theta to beta ratio (TBR) in frontal region of the brain.

Conclusion

VR intervention is useful in individuals with MCI or mild dementia and these findings demonstrate that VR‐intervention program is useful to improve cognitive and brain function, and physical function and gait speed in patients with cognitive decline. In future, longer and broader VR‐based studies are required to unfold a path to magnify the benefits of VR‐intervention for improving cognitive functions.
Répéter s'il vous plait: Working memory intensive sentence repetition deficits as a sensitive neuropsychological marker of primary progressive aphasia
Authors: Arslan Seckin , Plonka Alexandra , Cogordan Magali Payne , Manera Valeria , Gros Auriane , Meunier Fanny
Published: December 2020

Background

Sentence repetition deficits have been shown to be critical in diagnosing primary progressive aphasia (PPA), particularly the logopenic variant, distinguishing its symptoms from other Alzheimer’s disease related dementias [1‐3]. These impairments were found to be associated with working memory [4].

Method

In the current preliminary study, to further investigate how sentence repetition is mediated in memory in PPA and AD, we used a spoken sentence‐span task to examine groups of 6 French‐speaking PPA (including lvPPA and non‐fluent subtypes), 6 AD patients without aphasia, and 15 healthy ageing controls. The task required individuals to repeat meaningful French sentences with increasing number of content words ranging from three to nine. Each span of content words contained two items, and when the participants failed in repeating both items in one span, the task was terminated; when one item was incorrectly repeated half a point penalty was issued.

Results

Both the patient groups performed more poorly than healthy controls in all measures (ts>+/‐3.27). A set of mixed‐effects regression models showed that the PPA group had reduced sentence‐span (M
PPA=5.08 vs. M
AD=5.66; ß=0.58, SE=0.16, t=3.53, 95%CIs[0.25,0.91]), greater difficulty repeating content words (M
PPA= 44.33 vs. M
AD=50.00; ß=5.66, SE=2.19, t=2.57, 95%CIs[‐2.18,‐0.48]), and elevated number of substitution errors (M
PPA= 6.16 vs. M
AD=4.83; ß=‐1.33, SE=0.42, t=‐3.10, 95%CIs[1.32,10.01]) compared to the AD group (Figure 1). No group differences were found in repetition duration standardized by number of content words.

Conclusion

We found that sentence repetition deficits in PPA have different characteristics than those in AD, submitting to earlier studies that associated PPA assessment with graphic markers [5]. We recommend clinicians to incorporate a sentence repetition task involving sentences with varying length and number of content words in their diagnostic assessment as this study suggests that working‐memory intensive sentence repetition decline appears to be a neuropsychological clinical marker distinguishing cognitive profiles of PPA from AD patients. [1]Hohlbaum, et al., Aphasiology, 2018. 32(12):1445‐1467. [2]Foxe, et al., Cortex, 2016. 83: p.39‐50. [3]Gorno‐Tempini, et al. Neurology, 2008. 71(16): p.1227‐1234. [4]Beales, et al., Brain and Language, 2019. 194: p.1‐11. [5]Gros, et al., Alzheimer’s&Dementia, 2019. P1‐285(15): p.351‐352.
The complexity of DLB: U.S.‐based Dementia with Lewy Body Consortium
Authors: Leverenz James B , Bekris Lynn M , Berman Sarah , Fleisher Jori E , Galasko Doug R , Galvin James E , Goldman Jennifer , Hall Deborah A , Irwin David J , Kaufer Daniel , Lippa Carol , Litvan Irene , Lopez Oscar L , Sabbagh Marwan N , Tsuang Debby W , Zabetian Cyrus P
Published: December 2020

Background

The clinical syndrome of dementia with Lewy bodies (DLB) is well defined with good positive predictive value for the presence of Lewy body pathology at autopsy. However, the presence of Lewy body pathology in dementia is not always linked to the clinical syndrome of DLB, particularly early in the clinical course (e.g., prodromal and mild cognitive impairment), and co‐pathologies are quite frequent. This clinical and pathologic complexity leads to many challenges including early recognition and diagnosis, clinical management, and development of symptomatic and disease modifying therapies. To address these issues, a number of consortia have been established to longitudinally study DLB and related Lewy body diseases, including a US based Dementia with Lewy Bodies Consortium (DLBC).

Method

The U.S.‐based DLBC is a multi‐centered, NIH funded, project to longitudinally and systematically study subjects with DLB and mild cognitive impairment/high likelihood DLB (MCI‐DLB). The primary goal of the DLBC is to generate biospecimens linked to clinical, imaging, and neuropathologic characterization in a longitudinally followed cohort across the participating DLBC sites. Biofluids, including blood and cerebrospinal fluid (CSF), and data generated by the DLBC will be ultimately be available to investigators through the NINDS‐funded Parkinson’s Disease Biomarker Program.

Result

To date, one hundred and thirteen subjects have been enrolled in the DLBC. Preliminary results from the first ninety‐two subjects note a male predominance in the sample (82 of 92, 89%). At baseline visit, mean age was 69.4 (SD 7.1 years), baseline UPDRS‐MDS Part III was 28.9 (15.7 SD) and MoCA 20.4 (SD 5.4). Neuropathologic data are limited, but suggest that an elevated CSF p‐tau may assist in clinically differentiating DLB with or without high levels of Alzheimer’s disease pathology. Imaging results including volumetric MRI, amyloid imaging and DaTscan are pending.

Conclusion

The development of DLB cohorts, such as the US based DLBC, is essential to understanding the complexity and pathobiologic significance of the clinical syndrome, biomarker characteristics and imaging findings in patients with underlying Lewy body disease. These results continue to emphasize the importance of further development of biomarkers in DLB and related neurodegenerative disorders.
Validation and normative data of the Spanish version of the Face‐Name Associative Memory Exam (S‐FNAME): Findings from the Barcelona Brain Health Initiative
Authors: Alviarez‐Schulze Vanessa , Cattaneo Gabriele , Solana Javier , Pachón‐García Catherine , Tormos‐Muñoz Josep Mª , Alegret Montserrat , Pascual‐Leone Alvaro , Bartres‐Faz David
Published: December 2020

Background

Three previous studies administrated the Spanish version of the Face Name Associative Memory Exam task (S‐FNAME) to Spanish participants. Sanabria and collaborators, (2018) in their investigation on subjective cognitive decline individuals, reported associations between task performance and amyloid‐β (Aβ) burden, in accordance with the original publication (Renz et al., 2011). Alegret and colleagues (2015) provided normative data and psychometric characteristics, albeit the study was limited to subjects attending a memory clinic and included a reduced number of participants (N=110) with gender inequality distribution. The purpose of this study was to provide normative data and psychometric characteristics of the S‐FNAME in a larger independent sample of cognitively healthy individuals.

Method

S‐FNAME was administered, according to standardized procedure published by Alegret et al. (2015), to 513 cognitively volunteers (243 women, mean age= 52,67±7,04, age range 41‐65, years of education= 17,28±3,71) participating in a longitudinal prospective cohort study (Barcelona Brain Health Initiative; Cattaneo et al., 2018). Subjects with diagnosis of neurological or psychiatric disease, substance abuse or treatment with psychopharmacological drugs, MMSE < 27, and cognitive impairments were excluded.

Result

Factor analysis supported construct validity revealing two underlying components: face‐name and face‐occupation and explaining 95,36% of the total variance. Correlations between S‐FNAME and Rey Auditory Verbal Learning Test (RAVLT) were significant (ρ=.392, p=.00) and confirm its concurrent criterion validity. We also found weak and no significant correlations with other non‐memory cognitive tests supporting divergent criterion validity. Women showed better scores and S‐FNAME scales were positively correlated with years of education and negatively with age. Finally, we generated normative data for Spanish population aged 40–65 years.

Conclusion

S‐FNAME exhibits good psychometric properties, consistent with previous findings regarding factorial structure and correlation with other measures and socio‐demographics variables (Alegret et al., 2015; Amariglio et al., 2012), although we found association with education in contrast to previous publications. S‐FNAME could serve as useful tool to assess memory impairments in Spanish population both for research purposes and clinical practice, to examine healthy older adult population and capture subtle cognitive decline or memory dysfunction associated to abnormal brain aging.
Medin amyloid forms age‐associated aggregates in the brain vasculature and may contribute to cerebral β‐amyloidosis
Authors: Wagner Jessica , Degenhardt Karoline , Wild Katleen , Obermüller Ulrike , Haesler Lisa M. , Koppelmann Anna Julia , von Zweydorf Felix , Gloeckner Christian Johannes , Maxwell Rusheka , Rotermund Carola , Skodras Angelos , Madine Jillian , Davies Hannah A. , Del Turco Domenico , Deller Thomas , Kahle Philipp J. , Jucker Mathias , Neher Jonas J.
Published: December 2020

Background

The most common human amyloid is probably medin (AMed), which deposits in the aorta of nearly everyone above 50 years of age. Previous studies reported that medin amyloid may co‐aggregate and seed serum amyloid A. Because of this finding and its exceedingly high prevalence in the aging population, we studied whether medin aggregates form in the brain during aging and may interact with other age‐associated amyloids such as Aβ.

Method

In order to study the pathobiology of medin amyloid and its contribution to vascular and parenchymal amyloidosis, we first investigated the occurrence of medin in wildtype mice. Additionally, we used APP transgenic mouse lines and human tissue for immuno‐histochemical and immunoprecipitation experiments to study a potential protein‐protein interaction with Aβ.

Result

We find that medin deposits are prevalent in the human brain vasculature and seem to increase both with age and Aβ pathology. Moreover, co‐immunoprecipitation experiments indicate an interaction of Aβ and medin. Strikingly, we also observe that, similar to the human situation, amyloid‐like deposits of medin are formed in the aorta as well as in the brain vasculature of aging wildtype mice. Further experiments in APP transgenic mice showed that medin does not only co‐localize with Aβ Plaques and CAA, but may also promote cerebral β‐amyloidosis in mouse models of Alzheimer’s pathology.

Conclusion

Our findings suggest that age‐associated medin deposition occurs both in the mouse and human brain, where it may promote cerebral β‐amyloidosis.
Early diagnosis of Alzheimer's dementia with the artificial intelligence‐based Integrated Cognitive Assessment
Authors: Modarres Mohammad Hadi , Khazaie Vahid Reza , Ghorbani Mohammad , Ghoreyshi Amir Mohammad , AkhavanPour Alireza , Ebrahimpour Reza , Vahabi Zahra , Kalafatis Chris , Razavi Seyed‐Mahdi Khaligh
Published: December 2020

Background

We have developed the Integrated Cognitive Assessment (ICA), a 5‐minute, self‐administered, computerised test that is independent of language, cultural background and education and aims at screening for cognitive impairment in a way that can simplify and accelerate the diagnosis of Alzheimer's Dementia (AD) and Mild Cognitive Impairment (MCI). The ICA utilises artificial intelligence to analyse high‐dimensional clinical and demographic data.

Method

We carried out head‐to‐head studies comparing classification performance of the ICA with widely used cognitive assessments (MoCA and ACE) in participants with MCI and mild AD. The ICA test measures patterns of reaction time and categorisation accuracy which are utilised by an AI engine, alongside demographic data, to provide a predictive score about participant’s cognitive status. We also investigated the use of a deep (50 layers) neural network to extract informative features from the ICA test response patterns.

Result

On a population of 200 participants (84 healthy, 68 MCI, 48 mild AD), the ICA achieved an area under the ROC accuracy of 91% in distinguishing between healthy and impaired (MCI and mild AD) participants. In comparison MoCA achieved an AUC of 82%, and ACE 84%. Utilising the deep learning network for automatic feature extraction significantly improved the specificity and sensitivity compared to only using a linear classifier. The ICA Spearman correlation of 0.67 (p‐value <0.0001) with MoCA, and 0.73 (p‐value<0.0001) with ACE establishes convergent validity with these cognitive tests. ICA results were not biased by participants level of education (i.e. no significant correlation), whereas MoCA and ACE had correlations of 0.31 (p<0.0001) and 0.31 (p<0.001) respectively with the level of education in the same set of subjects.

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 has advantages over MoCA and ACE because of its shorter duration, automatic scoring and potential for medical record or research database integration. ICA’s AI engine is able to learn from additional data and utilise deep learning, further improving the predictive power of the ICA test.
Association between low gait speed and cognition decline in older nursing home residents
Authors: Li Ying , Yang Xue
Published: December 2020

Background

The gait speed represented the core determinant of physical function, which is reported to associated with cognitive decline. This study examined the association between gait speed and cognitive function in elderly nursing home residents.

Method

We conducted a cross‐sectional study in seven nursing homes in Western China. The cognitive states were measured by MMSE. The gait speed was measured via a 4m walking test, and appendicular muscle mass was estimated according to a previously validated anthropometric equation. Handgrip strength was measured with a handheld dynamometer. Dementia was defined as MMSE lower than 23. The cut‐off of the gait speed, appendicular muscle mass, handgrip strength was based on the sex‐specific 20% lowest percentile of the study population.

Result

Four hundred and ten participants were included. Two hundred and twenty‐three participants (54.39%) were identified as dementia. Compared with the subjects without dementia, the dementia subjects were more likely to have lower gait speed and grip strength (See Table 1).

As indicated in Table 2, compared with the normal gait speed subjects, low gait speed subjects exhibited an increased risk factor of dementia (OR: 3.75, 95% CI: 2.09‐6.72) in the unadjusted model. After adjusting for age, sex, education and other confounder, the low gait speed was an independent risk factor of dementia (OR: 2.71, 95% CI: 1.47‐5.00).

Conclusion

This study founded that low gait speed was significantly associated with dementia in older adults in nursing home. Screening for slow gait speed may be useful for identifying older nursing home residents at risk of cognition decline.
Functional hearing loss as a marker for early Alzheimer’s disease and dementia: Exploring the potential for reverse causation
Authors: Brenowitz Willa D , Filshtein Teresa J , Yaffe Kristine , Walter Stefan , Ackley Sarah F , Hoffmann Thomas , Jorgenson Eric , Whitmer Rachel A , Glymour M Maria
Published: December 2020

Background

Age‐related hearing impairment is associated with elevated Alzheimer’s disease (AD) and dementia risk. The hearing impairment ‐ dementia association may be due to underlying AD‐related neurodegeneration or shared risk factors that influence hearing loss (e.g. reverse causation or confounding). This is difficult to assess in traditional observational studies; we used genetic risk for AD as an analytic tool to explore the extent to which genetic risk also influences functional hearing loss.

Method

We studied 401,084 UK Biobank participants aged 40‐70, with Caucasian genetic ancestry, and enrolled 2007‐2010. Participants responded (yes, no) to the question “Do you have any difficulty with your hearing with background noise?” and a subset underwent a speech‐in‐noise hearing test. Participants were followed until 2018 for AD diagnosis (ICD‐9/10 codes). A genetic risk score for AD (AD‐GRS) was calculated as a weighted sum of 23 single nucleotide polymorphisms previously confirmed to be genome‐wide significant predictors of AD. We evaluated whether the AD‐GRS predicted hearing measures (evidence of reverse causation), using age‐, sex‐, and genetic ancestry‐ adjusted logistic and linear regression models and used the AD‐GRS in an instrumental variable analysis to estimate the effect of incipient AD on hearing impairment.

Result

Higher AD‐GRS was associated with difficulty hearing in ages 60+(OR= 1.03; 95%CI:1.00, 1.05) but not in adults <60 years (OR=1.00; 95% CI:0.98,1.03). AD‐GRS associations were also stronger in ages 60+ with poor speech‐in‐noise hearing (OR=1.06; 95%CI:1.00,1.11) and the AD‐GRS strongly predicted subsequent AD diagnosis in participants aged 60+ at enrollment (OR=4.19; 95%CI:3.80, 4.72). Using the AD‐GRS as an instrumental variable for AD diagnosis, we estimated that incipient AD increased probability of difficulty hearing at enrollment by 45% (95%CI: 1%, 93%).

Conclusion

Higher AD‐GRS was associated with slightly higher odds of difficulty hearing in addition to higher odds of AD diagnosis in later life. These trends were age‐related and analyses suggest that genetics that predispose for AD also influence functional hearing difficulty to some extent. Although these findings do not rule out hearing loss as a cause of dementia, they support the hypothesis that disease process related to AD also influences hearing difficulty before dementia onset.
The effect of APOE ɛ4 in Alzheimer’s disease biomarkers in Down syndrome
Authors: Vilaplana Eduard , Videla Laura , Carmona‐Iragui Maria , Benejam Bessy , Barroeta Isabel , Fernandez Susana , Altuna Miren , Pegueroles Jordi , Montal Victor , Bejanin Alexandre , Iulita M. Florencia , Valldeneu Sílvia , González‐Ortiz Sofía , Muñoz Laia , Camacho Valle , Videla Sebastián , Alcolea Daniel , Blesa Rafael , Lleó Alberto , Clarimon Jordi , Fortea Juan
Published: December 2020

Background

The APOE ɛ4 allele is the main genetic risk factor for sporadic Alzheimer’s disease (AD). However, its influence on AD in Down syndrome (DS) has received less attention. Our main objective was to study the effect of the APOE ɛ4 allele in AD biomarkers in a population‐based cohort of adults with DS.

Method

Cross‐sectional study. We selected adults with DS and euploid healthy controls from Hospital de Sant Pau, Barcelona. We included all participants with known APOE genotype and at least one biomarker measured in: plasma, CSF or neuroimaging (MRI, FDG‐PET or Florbetapir‐PET). DS participants were classified into asymptomatic and symptomatic (prodromal or AD dementia). Aβ1‐42, total‐tau and NfL levels were measured in plasma using SIMOA and in CSF using Lumipulse. We extracted mean FDG‐PET SUVR (Landau), we measured the Centiloid score for Florbetapir‐PET and the adjusted hippocampal volumes from MRI. Subjects were classified into APOE ɛ4 carriers and non‐carriers. We compared age of symptoms onset between APOE ɛ4 carriers vs non‐carriers, and we fitted within‐group local regression models to compare the association of biomarkers with age between groups.

Result

We included 325 individuals with DS (214 asymptomatic and 111 symptomatic) and 239 controls (Table 1). When comparing age at diagnosis, subjects with DS harboring at least an APOE ɛ4 allele were two years younger than non‐carriers (51.1 vs 53.2, p=0.08). We then compared biomarker trajectories between APOE ɛ4 carriers and non‐carriers. As displayed in Figure 1, subjects with DS harboring an APOE ɛ4 allele showed earlier decreases in CSF Aß1‐42 and increases in Florbetapir Centiloid. APOE ɛ4 carriers showed a steeper decline in brain metabolism (FDG‐PET SUVR) in the fifth decade compared to APOE ɛ4 non‐carriers. No differences were found in total‐tau and NfL in CSF or plasma, or in hippocampal volume trajectories.

Conclusion

APOE ɛ4 allele may influence the onset of AD‐related symptoms in DS. This effect might be due to earlier amyloid deposition and brain hypometabolism. The presence of APOE ɛ4 does not seem to have an effect on total‐tau, NfL or hippocampal volume. In conclusion, these results provide further insight on the relationship between APOE ɛ4 and AD pathophysiological processes.
Multimodal behavioral analysis for early detection of Alzheimer’s disease: A preliminary result
Authors: Yamada Yasunori , Shinkawa Kaoru , Ishikawa Tatsuya , Nishimura Masafumi , Nemoto Miyuki , Tsukada Eriko , Ota Miho , Nemoto Kiyotaka , Arai Tetsuaki
Published: December 2020

Background

With the rapid growth in the elderly population worldwide, early detection of Alzheimer’s disease (AD) has become increasingly important. In this respect, behavioral analysis of sensor data is expected to extend opportunities for assessments and help identify subtle changes resulting from AD at an early stage. Gait, speech, and drawing behaviors have been actively investigated and recognized as behavioral biomarkers that can be used for detecting individuals with AD and mild cognitive impairment (MCI). However, previous studies have mainly investigated single types of behavior. It remains unclear whether combining multimodal behavioral data could improve detection performance.

Method

In this study, we collected multimodal behavioral data related to gait, speech, and drawing from 73 Japanese seniors consisting of 36 healthy controls (HC), 26 MCI, and 11 AD. For gait data, we collected motion capture data during 9‐meter walks at the usual walking pace and extracted gait features related to pace, rhythm, variability, and postural control. Speech data were collected while performing tablet‐based cognitive tasks consisting of verbal fluency, calculation, and picture description, followed by extraction of acoustic, prosodic, and linguistic features. We also collected drawing behaviors with a drawing tablet during five tasks including clock drawing and trail making, and obtained features related to kinematic parameters of drawing trajectories and drawing pressure. We then used these features to build binary classification models for differentiating MCI or AD from HC using a support vector machine model with a feature selection method. The models were then evaluated by ten‐fold cross‐validation.

Result

Our models using features of three types of behavior achieved 99.8% accuracy for HC vs. AD and 92.0% accuracy for HC vs. MCI. Compared to models using single modality behavioral data, we found that our model improved detection by up to 9.1% for HC vs. AD and 21.0% for HC vs. MCI.

Conclusion

We demonstrated that multiple behavioral data could improve detection accuracy for patients with both MCI and AD by capturing different functional changes resulting from AD. Our approach based on multimodal behavioral analysis shows promise for timely diagnosis at an early stage of AD.
Self‐reported hearing impairment and social isolation are potentially modifiable risk factors for cognitive decline in community‐dwelling older adults
Authors: Tay Laura , Bakar Huda Mukhlis Abu , Ho Jolene , Latib Aisyah , Tay EeLing , Mah Shimin , Chan HiuNam , Ng YeeSien
Published: December 2020

Background

Frailty is a state of excess vulnerability to stressors, and has been associated with increased risk of late‐life cognitive decline. As a multi‐factorial condition which is potentially reversible, frailty represents a modifiable target for prevention of cognitive impairment. We examine the risk of cognitive decline associated with physical frailty and its contributing factors in community‐dwelling older adults.

Method

In this prospective cohort study, community‐dwelling older adults aged >55 years undergo a rapid geriatric assessment that includes social profiling, cognitive (modified Chinese Mini‐Mental State Examination, CMMSE), psychological (Geriatric Depression Scale, GDS), nutritional (Mini Nutritional Assessment‐Short Form, MNA‐SF), and sensory (self‐reported vision, hearing) assessment at baseline and 1‐year. Sarcopenia was assessed using SARC‐F and participants completed a battery of physical fitness tests for flexibility, grip strength, upper limb dexterity, lower limb strength/ power, balance and endurance at baseline and follow‐up. Physical frailty was defined using modified Fried criteria. Cognitive decline was defined as a loss of >2 points on CMMSE at 1‐year relative to baseline.

Result

229 participants (mean age 67.3+7.0years) completed 1‐year follow‐up. 28 (12.2%) participants exhibited cognitive decline. Age, gender and education were similar between groups with and without cognitive decline. There was no difference in baseline prevalence of frailty, sarcopenia, depression and malnutrition between groups. Self‐reported hearing impairment at baseline was significantly more prevalent amongst older adults exhibiting cognitive decline (39.3% vs 19.9%, p=0.009), and they were more likely to report having no contact with friends or relatives compared with their counterparts with stable cognition (10.7% vs 1.0%, p=0.001). On physical fitness tests, only poorer upper limb dexterity at baseline was significantly associated with risk for cognitive decline (box‐and‐block test: 50.3+10.3 vs 54.5+9.6, p=0.035). In multiple logistic regression adjusted for age, gender, education and baseline cognitive performance, self‐reported hearing impairment independently increased risk for cognitive decline (OR=3.29, 95% CI 1.36‐7.96), while maintenance of social contact was protective (OR=0.04, 95% CI 0.00‐0.42).

Conclusion

While physical frailty was not associated with cognitive decline over the relatively short follow‐up of 1‐year, hearing impairment and social isolation are potentially modifiable and should be targets of intervention to reduce cognitive decline in community‐dwelling older adults.