bluuebunny/crossref_metadata_2025 huggingface dataset:
A large genetic screen in flies uncovers human modifiers of Aβ42 and tau toxicity
Authors: Varte Vanlalrinchhani , Munkelwitz Jeremy W , Scott Raymond , Limas Diego E Rincon
Published: June 2023

Background

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by dementia and cognitive decline due to progressive cerebral cortical atrophy. Brains of AD patients are characterized by the accumulation of microscopic extracellular amyloid‐beta (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. The deposition of Aβ42, which is one of the fragments of amyloid precursor protein (APP), has been known to play a role in initiating the events leading to the formation of amyloid and subsequently hyperphosphorylation of tau. However, animal models expressing either Aβ42 or tau individually do not mimic the complexity of the human condition. Indeed, recent evidence suggests that Aβ42 and pathological tau interact synergistically to modulate neurotoxicity in AD.

Method

To shed light on their concerted roles in AD pathogenesis and to discover pathways mediating Aβ42 and tau interactions, we generated transgenic flies co‐expressing human Aβ42 fused to a signal peptide along with the longest wild‐type tau isoform.

Result

Overexpression of Aβ42 or tau in Drosophila using the UAS‐Gal4 system causes mild to the moderate rough eye. In comparison, co‐expression of Aβ42 with tau causes severe roughening and reduction of the eye size. The level of neuronal cell death in eye tissues was also significantly enhanced in flies co‐expressing Aβ42 and tau. To identify pathways mediating Aβ42+tau interactions, we are currently using the Aβ42+tau eye phenotype as platform to screen 1,500 UAS lines expressing a variety of human genes.

Conclusion

We have identified few enhancers and suppressors not previously known to be involved in AD pathogenesis, which will be helpful to uncover new molecular pathways and potential therapeutic targets. This work is supported by NIH grant R21AG069050 to DERL.
Construction of the MIITRA T1‐weighted and DTI templates of the older adult brain in a common space at 0.5mm resolution
Authors: Wu Yingjuan , Ridwan Abdur Raquib , Niaz Mohammad Rakeen , Bennett David A , Arfanakis Konstantinos
Published: June 2023

Background

High resolution multimodal MRI templates of the older adult brain have the potential to facilitate template‐based studies of aging. As part of the Multichannel Illinois Institute of Technology & Rush university Aging (MIITRA) atlas, the present work developed high quality 0.5mm isotropic resolution T1‐weighted (T1w) and diffusion tensor imaging (DTI) templates in common space using data from a large, diverse, community cohort of non‐demented older adults.

Method

Data

T1w and DTI data were collected using two 3T MRI scanners on 400 non‐demented older adults (50% male;64.9‐98.9 yrs;54% white,43% black) (Bennett et al.,2018; Barnes et al.,2012).

Template construction

Step1: An unbiased initial T1w template was created by pairwise affine registration (Ridwan et al.,2021).

Step2: Spatial normalization was driven by T1w and DTI data alternatively (Wu et al., 2019). All transformations were combined to minimize interpolations and applied to both modalities. A patch‐based tissue‐guided sparse‐representation approach was employed to compute the template (Ridwan et al.,2021).

Step3: High spatial resolution templates were created based on principles of super‐resolution (Niaz et al.,2022)

The resulting templates are referred to as MIITRA_0.5mm templates.

Evaluation

T1w and DTI data from 202 ADNI3 non‐demented older adults were used for evaluation.

The MIITRA_0.5mm templates were compared to other high resolution templates and the templates including older adults in terms of image sharpness and spatial normalization accuracy of ADNI3 data when each template was used as a reference for normalization.

Result

MIITRA_0.5mm templates exhibited higher image sharpness (Fig.1,2). MIITRA_0.5mm templates allowed the highest inter‐subject spatial normalization accuracy across spatially normalized ADNI3 data and required less deformation than other high‐resolution templates (Fig.3,4). It should be noted that 1mm templates require on average less deformation than high‐resolution templates because larger voxels limit local deformations. Finally, the MIITRA_0.5mm templates allowed higher inter‐modality spatial matching of normalized older adult data (Fig.5).

Conclusion

This work developed high resolution T1w and DTI multimodal templates of the older adult brain for the MIITRA atlas. The new templates exhibited higher image quality, were more representative of the older adult brain, and allowed higher spatial normalization accuracy compared to other templates. The new templates will be available for download at www.nitrc.org/projects/miitra.
Frailty in Relation to Cognition in Community‐Dwelling Older Adults: Validating the Electronic Frailty Index based on the Comprehensive Geriatric Assessment (eFI‐CGA) in Primary Care
Authors: Song Xiaowei , Park Grace , Clarke Barry , Rockwood Kenneth
Published: June 2023

Background

Frailty can be screened using the Clinical Frailty Scale (CFS) and quantified using a Frailty Index (FI) based on deficit accumulation. Higher degrees of frailty have been associated with greater risks of adverse outcomes, including dementia. Comprehensive Geriatric Assessment (CGA, allows development of individualized care plans for older adults’) has been used to derive an FI‐CGA. To promote effective assessment of frailty outside specialized geriatric services, we developed and are validating an electronic CGA with an automated electronic FI‐CGA (eFI‐CGA). The goal is early detection and management of frailty in home‐living older adults. Here, we examined the characteristics and robustness of the eFI‐CGA assessed by primary‐care physicians and investigated the relationship between the eFI‐CGA and cognition.

Method

Data were collected as part of the collaborative effort between Fraser Health and Nova Scotia Health to validate the eFI‐CGA. Baseline assessments were conducted at primary care clinics using eFI‐CGA software tools with the eFI‐CGA created following standard procedures. Dementia diagnoses on no cognitive impairment (NCI), mild cognitive impairment (MCI), and dementia were made following DSM‐IV criteria. For robustness testing, multiple interactions of the eFI‐CGA were generated, excluding cognitive measures. Data were analyzed employing regression and descriptive statistics.

Result

The sample (n = 137; age = 79.2±7.6 years, women = 67.9%; CFS = 3.7±1.3) contained 82.5% NCI and 17.5% MCI/dementia cases. Participants with MCI/dementia were slightly older, less educated, more likely to live alone and take 7+ medications, compared to those with NCI. Sores of the various integrations of the eFI‐CGA were highly correlated. These showed consistent distributions, age relationships, and the maximum values <0.70. The NCI group showed the lowest mean eFI‐CGA scores consistently across the iterations. Close correlations of the eFI‐CGA with the CFS (p<0.001) and the mini‐cog (p<0.010) were observed.

Conclusion

The characteristics of the eFI‐CGA in primary care were consistent with those widely reported for the FI. A clear association between the eFI‐CGA and cognition was found, even when cognitive measurements were excluded from the eFI‐CGA. Ongoing work will test the generalizability of these findings, with a larger sample size and follow‐up assessments and outcomes, as well as examine how primary care CGA data compared with geriatrician assessments.
Meta‐analysis of high‐clearance anti‐amyloid immunotherapies trials in early Alzheimer’s disease: A significant clinical effect but a low benefit/risk ratio
Authors: Villain Nicolas , Planche Vincent
Published: June 2023

Background

In the last three years, three over four phase II or III clinical trials using high‐dose anti‐amyloid immunotherapies in early Alzheimer’s disease (AD) have turned out to be positive on clinical outcomes: aducanumab (one of two), donanemab, and lecanemab. These results contrast with the previous failures of anti‐amyloid immunotherapies. Despite different pharmacodynamic properties, these drugs share a new characteristic: the high clearance of amyloid load as measured with amyloid positron emission tomography. In the meantime, the Food and Drug Administration’s conditional approval of aducanumab has led to unprecedented scientific controversies.

Method

We used the data from the highest dose group (i.e., the groups used for approval application or ongoing phase III trials) versus placebo after 18 months of the lecanemab and donanemab phase II trials and of the two aducanumab phase III trials to perform a meta‐analysis. Regarding clinical efficacy, we analyzed the CDR‐SB, ADASCog, and MMSE data. Regarding safety, we analyzed the occurrence of any Amyloid‐Related Imaging Abnormalities (ARIA), of ARIA‐edema (ARIA‐E), of ARIA‐hemorrhage (ARIA‐H), and of symptomatic and serious ARIA. The analyses were performed using RevMan 5.4.1 and a random effect model.

Result

High‐clearance anti‐amyloid immunotherapies were shown to significantly slow down cognitive decline after 18 months as measured with CDR‐SB (weighted mean = ‐0.24 points; p = 0.04), and ADAS‐Cog (weighted mean = ‐1.25 points; p = 0.0003), but not with MMSE (weighted mean = +0.31 points; p = 0.23) when compared to placebo. In parallel, the drugs significantly increased the occurrence of any ARIA (risk ratio = 3.68; p<0.0001), of ARIA‐E (risk ratio = 13.39; p<0.0001), of ARIA‐H (risk ratio = 2.78; p = 0.0002), and of symptomatic and serious ARIA (7/1321 = 0.53% in the high dose groups versus 0/1446 in the placebo groups; risk ratio = 6.44; p = 0.04).

Conclusion

When pooled together, the data from high‐clearance anti‐amyloid immunotherapies trials confirm a significant clinical effect after 18 months. However, this effect remains below the established minimal clinically relevant values. Safety remains an issue with 0.5% of symptomatic and serious ARIA, significantly beyond chance, despite thorough in‐trial monitoring and management. The benefit/risk ratio of this class of drugs in early AD is thus questionable after 18‐months. Identifying subgroups of better responders and the perspective of combination therapies may help improve their clinical relevance.
Cognitive screening among older afro‐caribbean adults in rural areas of South Florida
Authors: Daniel E. Valerie , Wiese Lisa Ann Kirk , Galvin James E
Published: June 2023

Background

Alzheimer’s disease and related dementias (ADRD) disproportionately affects communities of color with older black Americans performing worse than Whites on cognitive tests and facing higher ADRD risks.1,2 Contributors to low diagnostic rates include inadequate knowledge, cultural norms, low health literacy, and an unwillingness to discuss early signs of disease. 1,3‐5 Older Afro‐Caribbeans are a growing subset of the population, particularly in rural South Florida, but best practices to screen for ADRD are unknown.6 Many instruments, including the Montreal Cognitive Assessment (MoCA) have not been assessed within this population. We report on the use of the MoCA 5‐minute test/telephone (Mini‐MoCA) as a screening tool in older, rural‐dwelling Afro‐Caribbeans.7

Method

We conducted survey interviews with 53 Afro‐Caribbean participants. Participants were assessed with the 5‐minute Mini‐MoCA, which included tests of language fluency, orientation and recall. Linear regression models were used to investigate the association between different components of the Mini‐MoCA its effects on age, sex, and education.

Result

A total of 53 Afro‐Caribbean participants (67.2 +10.8y (Mean ± SD), 68% with 10y or less of education) residing in rural South Florida within the last 20 years were included. Participants were largely from Haiti (66%) with 34% from other Caribbean countries including Cuba, Jamaica, Puerto Rico, and Barbados. About 80% of participants reported not having their memory tested prior to the study. The Mini‐MoCA demonstrated good reliability in this sample (α = 0.734). We found that 53% had a total score of 11 or lower on the Mini‐MoCA. Linear regression suggested a significant association between Mini‐MoCA score and education (p = .001).

Conclusion

While the Mini‐MoCA showed good reliability in low‐educated older Afro‐Caribbeans, scores were strongly dependent on years of education. Disparities in educational attainment may contribute to disparities in performance and affect true detection on cognitive impairment in these communities. Social and cultural factors must be considered when interpreting the Mini‐MoCA, given the high error rates on items that depend on the ability to read and write. Study results highlight the need to use a language‐neutral test to accurately measures cognitive impairment among this specific population.
Testing for acceptance of an assistive social robot for dementia and caregiving
Authors: Mitchell Kimberly M , Zhao Xiaopeng
Published: June 2023

Background

Approximately 5.8 million older adults in the U.S. are living with AD and it is estimated that by 2060, this number is projected to triple. People with AD often require high levels of care and assistance to maintain daily activities. The majority of care provided to a person living with AD or other forms of dementia is from a family caregiver, representing 18.6 billion hours of unpaid care valued at $244 billion. The long duration, time‐intensive nature of caregiving imposes high burdens on caregivers. There is a great need for assistive technologies and innovative solutions for the future of dementia care because of the increasing rise in adults with dementia.

Method

A multidisciplinary team of faculty and undergraduate and graduate students was created to design a low‐cost social robot to serve as assistive companions for people with AD. Focus group meetings with caregivers and those with beginning stages of dementia were held, where the team worked in identifying the audience’s needs and robot’s responsibilities. Initial sketches were formulated before being brought to life in Fusion 360 as 3D CAD objects and printed using a 3D printer. Several rounds of iterations of the social robot’s body and user interfaces were created and two final robot designs were tested with undergraduate students (N = 15) for general attitudes of acceptance and feelings of overall experience.

Result

Results from our user testing showed that users preferred one design more than another. Users wanted options in their interactions – having the ability to have speech conversation and touch‐screen abilities. Overall, the results from the user testing were positive, and the team is currently working on a final robot design before testing at nursing homes and assisted living facilities.

Conclusion

Estimated to be less than $300, our socially assistive robot holds promise to help address the disparity issues in the underserved.
Peripapillary retinal nerve fiber layer and macular outer retinal layers are reduced in cognitively unimpaired older adults at high risk of AD. Preliminary results from a five ‐year longitudinal study
Authors: Arthur Edmund , Alber Jessica , Thompson Louisa I , Strenger Jennifer , Montgomery Catrina , Sinoff Stuart , Salloway Stephen P. , Snyder Peter J
Published: June 2023

Background

The retina, an extension of the central nervous system, shows promise for development of non‐invasive, low cost AD risk screening biomarkers. Most studies do not answer the question of whether retinal biomarkers are useful in the pre‐symptomatic phase of AD for assessment of early disease risk. In this study1, we investigated structural changes in the retinal neural layers between low and high risk cognitively unimpaired (CU) older adults using Spectral Domain Optical Coherence tomography (SD‐OCT).

Method

These data were provided from an ongoing trial that will conclude enrolment in the summer of 2022.1 Macular (30×25‐degree) and optic disc centered (radii of 3.5, 4.1, and 4.7 mm) SD‐OCT images of 13 CU low risk (age mean: 67 years; range: 56‐75 years) and 60 CU older adults at high risk for AD (age mean: 66 years; range: 55‐81 years; no significant difference in age between the two groups, p = 0.43) were acquired using the Spectralis imaging device. Participants had MoCA score ≥ 26, and RBANS‐U DMI score ≥ 85. Vendor software was used to segment and compute average retinal thickness in the 9 ETDRS maps for the macular and 7 glaucoma fields for the optic disk. Independent sample t test was used to compare retinal layer thickness between the two groups. A p‐value < 0.05 assessed statistical significance. Cohen’s d served as effect size measure.

Result

In the macular region, there were reduced retinal volume/thickness measurements for high risk vs. low risk CU older adults (outer plexiform layer volume in the inner inferior region; 0.054 vs. 0.062 mm3, p = 0.047, d = 0.62; central outer nuclear layer, ONL thickness; 97 vs. 102 µm, p = 0.041, d = 0.64; central ONL volume; 0.076 vs. 0.16 mm3, p = 0.023, d = 0.71). In the peripapillary region, there was reduced retinal nerve fiber layer (RNFL) thickness in the temporal region for high risk vs. low risk CU older adults (3.5 mm radius; 66.7 vs. 75.6 µm, p = 0.011, d = 0.80; 4.1 mm radius; 59.7 vs. 68.3 µm, p = 0.006, d = 0.87; 4.7 mm radius; 54.2 vs. 62.2 µm, p = 0.006, d = 0.87).

Conclusion

Our initial analysis shows reduced peripapillary RNFL and macular outer retinal layers in CU high risk vs. low risk group.
Modelling the developmental trajectories of cognitive reserve in children
Authors: Irani Zubin , Sheridan Andrew , Silk Tim , Weinborn Michael , Gavett Brandon E
Published: June 2023

Background

Cognitive reserve (CR) is thought to protect cognitive ability against neurodegenerative conditions, such as Alzheimer’s disease, or other neurological insults. Because past research has studied the construct extensively in older adult populations, little is known about its development across the lifespan. The current study generated a dynamic CR index based on a modified residual approach utilised successfully in older adults (Reed et al., 2010; Bettcher et al., 2019), and examined its criterion and construct validity in a paediatric cohort comprising children both with and without ADHD.

Method

Archived longitudinal data collected across 2011‐2019 from N = 115 children (MAge = 10.48, SDAge = 0.61, n = 72 [63%] male, n = 43 [37%] with ADHD) was obtained from the Murdoch Children’s Research Institute. Static and dynamic CR were operationalised based on residual variance in (change in) fluid intellect (Matrix Reasoning) not explained by demographics (i.e., sex and age) or MRI‐based brain variables (i.e., grey matter volumes, white matter hypointensities [WMH], and hippocampal volumes). This index was subsequently used to predict relevant outcome variables (i.e., sustained attention, working memory, inhibition, word reading, and mathematical computation) to assess criterion validity at baseline and across time, while construct validity was assessed via interaction effects between CR, brain, and baseline/longitudinal outcomes.

Results

Approximately 8% of the variance in fluid intellect was predicted by selected brain and demographics at baseline, with 14% predicted in the longitudinal model. CR at baseline predicted mathematical computation (p<.001), word reading (p = .012), and working memory ability (p<.001) at baseline. CR change only predicted change in word reading ability (p<.001); it was also found to moderate relationships between WMH volume change and word reading trajectory, and between WMH volume change and change in sustained attention performance.

Conclusion

Our results suggest that CR can be modelled in children using a residual index, but with less validity than in older adults; weak criterion and construct validity were evident, although this should be tempered by the fact that there was minimal variance explained in the residualised variable. An adjusted model optimised for a paediatric cohort will form the basis of further inquiry into the study of CR in a developmental context.
Prediction of vascular injury and the impact of physical activity on the association between Primary ALdosteronism and cerebral Microbleeds (PALM)
Authors: Lee Sun Min , Jeon Ja Young , Park Sun Ah , Choi Jin Wook , Chung Seung Ah , Han Seung Jin , Moon So Young
Published: June 2023

Background

Primary aldosteronism(PA) induces hypertension and vascular injury. Cerebral microbleed(CMB) is a representative form and can cause cognitive decline over the long term. This study is to investigate vascular damage in PA. Regarding physical activity, a preventive factor for vascular damage and known to increase aldosterone itself, we evaluated difference between aldosteronism and CMB depending on level of usual physical activity.

Method

We recruited PA diagnosed patients aged 13 years or older, who visited Endocrinology clinic in the past 3 years. We excluded patients with other causes of hypertension and major brain lesion. Brain magnetic resonance imaging(MRI), and physiological tests were performed: transcranial doppler(TCD), peak wave velocity(PWV), and sonographic endothelial function test(SEFT). In addition, we performed funduscopy for detecting retinal microhemorrhage, and Korean version of Montreal Cognitive Assessment(K‐MoCA), Clinical Dementia Rating(CDR), Clinical Dementia Rating sum of boxes(CDR‐SOB) for cognitive assessment. Physical activity was investigated using global physical activity questionnaire.

Result

Total 41 participants (age, 46.0±13.4years; 46.3% of male; BMI, 25.8±3.4kg/m2; education, 13.8±2.2years) were enrolled. The mean duration of PA was 1.7±1.7years, and serum findings at diagnosis were as follows: renin (0.5±0.4ng/ml/hr), aldosterone concentration (318.6±203.3pg/mL), potassium (3.6±0.8mMol/L), aldosterone‐to‐renin ratio (91.5±73.7). In 30 of 41 patients, adrenal masses were observed on abdominal Computed Tomography(number, 1.3±0.6; size, 14.8±5.0mm). There were participants with vascular risk factors: hypertension(38, 8.1±6.4), diabetes mellitus(3, 2.5±1.8), and dyslipidemia(2, 7.7±5.8). 1 participant each had been diagnosed with myocardial infarction and cerebrovascular disease. 10 participants had a smoking history (7.8±12.3pack years), and 24 had a drinking history, with the average frequency of drinking per week was 1.2±1.4. Cognitive status was assessed by K‐MoCA(26.8±2.5), CDR(0.2±0.2) and CDRSOB(0.2±0.2). Moderate‐to‐vigorous physical activity was 192.2±246.7 minutes per week. CMB was confirmed in 10 and lacune in 7 cases. There were 9 participants who showed white matter change in Fazekas grade 1‐2. Physiological tests showed abnormality in 1 patient in TCD, 7 in PWV(baPWV, 14.1±1.9 m/s), and 6 in SEFT(flow mediated dilation, 6.6±1.3%).

Conclusion

It is expected that more data will be collected through additional participant recruitment and evaluation. It remains to be seen that the analysis with additional data will yield results to test the hypothesis.
Role of neurofilament light chain to reduce diagnosis and improve outcomes for patients in a real‐world cognitive neuropsychiatry service: A retrospective MiND study
Authors: Kang Matthew , Eratne Dhamidhu , Dobson Hannah , Keem Michael H , Li Qiao‐Xin , Loi Samantha M , Tsoukra Paraskevi , Masters Colin L. , Collins Steven J , Velakoulis Dennis
Published: June 2023

Background

It is common for patients presenting with neuropsychiatric symptoms to endure significant diagnostic odyssey. Neurofilament light chain (NfL) has shown promise in being able to differentiate between neurodegenerative and psychiatric disorders. This study aimed to assess the clinical utility of NfL in avoiding misdiagnosis.

Method

In this retrospective study, we conducted file review of patients assessed at Neuropsychiatry, Royal Melbourne Hospital between 2009 to 2020. We included all patients (n = 212) who had a CSF NfL level at their baseline assessment. Investigators blinded to NfL levels extracted clinical information including diagnoses from the initial and follow‐up assessments using documentation available. In addition, we collected follow‐up data from external services where available. Initial and follow‐up/final diagnoses were categorised as neurodegenerative disorder (ND), psychiatric disorder (PSY), mild cognitive impairment (MCI), unclear, and not‐neurodegenerative (Not‐ND). Not‐ND were individuals who did not meet the diagnosis for PSY or MCI, and did not have worsening symptoms. Based on our previous findings, we defined an NfL>582pg/mL as a positive test result for ND.

Result

So far, we have collected information from 135 patients. Of these, 14/89 (16%) patients initially diagnosed with ND were re‐diagnosed as PSY or Not‐ND. 2/30 (7%) patients initially diagnosed with PSY were re‐diagnosed as having ND. Including MCI and unclear, 32/135 (24%) had a delayed diagnosis, which could have been reduced to 14% based on baseline CSF NfL predicting ND or Not‐ND/MC/PSY. Data analysis is ongoing and full results will be presented at the conference.

Conclusion

Baseline CSF NfL could have aided clinicians in a real‐world clinical setting, to reduce misdiagnosis, and increase diagnostic accuracy from 76% to 86%. An elevated level could prompt assertive investigations for neurological and neurodegenerative causes. Conversely, a low NfL, could reassure against a neurodegenerative disorder, preventing unnecessary assessments. Timely and accurate diagnosis will improve outcomes and precision care for patients and families.
In vivo brainstem tau pathology is related to entorhinal amyloid pathology in middle‐aged healthy participants
Authors: Meyer François , Justinas Narbutas , Van Egroo Maxime , Dapnée Chylinski , Bahri Mohamed Ali , Ekaterina Koshmanova , Besson Gabriel , Vincenzo Muto , Christina Schmidt , Luxen André , Phillips Christophe , Pierre Maquet , Gilles Vandewalle , Collette Fabienne , Bastin Christine , Salmon Eric
Published: June 2023

Background

Braak’s model of Alzheimer’s disease (AD) progression suggests that the initial accumulation of hyperphosphorylated tau protein is seen in the locus coeruleus (LC). Tau pathology might be a good marker of subsequent cognitive decline in initially unimpaired participants. We capitalized on Braak’s model to assess in a sample of cognitively unimpaired late‐middle‐aged individuals, the relationship between tau and Aß accumulation in the locus cœruleus, basal forebrain (BF) and entorhinal cortex (ERC).

Method

65 participants aged 50‐70 years were enrolled in a multimodal cross‐sectional study investigating the relationship between AD neuropathology, cognitive aging and cognitive complaints, and life style.

MRI acquisitions were performed on a 3‐T scanner (MAGNETOM Prisma, Siemens). Tau and Aß‐PET were performed on an ECAT EXACT+ HR scanner (Siemens). [18F]THK5351‐PET was used as a proxy of tau accumulation and Aß‐PET radiotracer was [18F]Flutemetamol.

Masks were used for entorhinal cortex (ERC), basal forebrain (BF) and locus cœruleus (LC). We extracted Tau and Aß burden in each region of interest, for a total of ten neuroimaging AD biomarkers (LC‐Tau, LC‐Aß, BF123‐Tau, BF123‐Aß, BF4‐Tau, BF4‐Aß, right and left ERC‐Tau, right and left ERC‐Aß).

Statistical analyses. All statistical analyses were performed with SAS 9.4 for Windows (SAS Institute, Cary, NC, USA) using the GLIMIX model.

Result

We found direct correlations between LC‐tau and left ERC‐Aß (F = 6.86, p = .0112) or LC‐tau and right ERC‐Aß (F = 14.12, p = .0004), and also between LC‐Tau and BF4‐Aß. However, a model including the interactions between LC‐Tau, BF4‐Aß and ERC‐Aß, was not significant. Stepwise analysis confirmed a significant liability of the model to explain ERC‐Aß (F = 5.86, p = .0048 for left and F = 6.83, p = .0005 for right ERC, for which LC‐tau had the main contribution (F = 14.12, p = .0004).

Conclusion

Our results showed a positive and significant correlation between Tau burden in the LC and amyloid burden in the ERC. The relationship between these two AD biomarkers was observed in healthy individuals without any cognitive impairment.
Undiagnosed Alzheimer’s disease and related dementias among foreign‐born Middle Eastern and North African adults in the United States
Authors: Kindratt Tiffany B , Dallo Florence J , Zahodne Laura B. , Ajrouch Kristine J
Published: June 2023

Background

Alzheimer’s disease and related dementias (ADRD) disparities exist by race/ethnicity and nativity (Mehta & Yeo, 2017). Non‐Hispanic blacks and Hispanics are more likely to have ADRD and to be undiagnosed than non‐Hispanic whites (Amjad et al., 2018; Gianattasio et al., 2019). The prevalence of undiagnosed ADRD among Middle Eastern and North African (MENA) adults in the US remains unknown. MENA men tend to report better health than women regardless of immigrant status (Read & Reynolds, 2012). Our aims were to: 1) estimate and compare estimates of suspected undiagnosed ADRD among foreign‐born MENA adults compared to US‐ and foreign‐born non‐Hispanic whites and 2) compare estimates stratified by sex.

Method

We linked data from the 2000‐2017 National Health Interview Survey and 2001‐2018 Medical Expenditure Panel Survey (ages > = 65 years, n = 23,981). ICD‐9 (290/294/331/797) and ICD‐10 (F03/G30) codes were used to measure ADRD diagnosis. Undiagnosed ADRD was suspected if a participant reported having a cognitive limitation without a corresponding ADRD diagnosis. Bivariate and multivariable logistic regression analyses adjusted for age, sex, and potentially modifiable risk factors (education, hearing loss, hypertension, depression, social isolation, and diabetes) were conducted.

Result

The prevalence of suspected undiagnosed ADRD was highest among foreign‐born MENA adults (15.8%) compared to US‐ (8.1%) and foreign‐born (11.8%) non‐Hispanic whites. The age‐adjusted and sex‐stratified prevalence of suspected undiagnosed ADRD was higher among MENA women (22.5%) than MENA men (9.3%) and lowest among US‐born white men (7.6%). In fully adjusted logistic regression models, foreign‐born MENA adults had 1.98 times greater odds (95% CI = 1.09‐3.60) of undiagnosed ADRD compared to US‐born non‐Hispanic whites. There were no differences between foreign‐born MENA men and US‐born non‐Hispanic white men. Foreign‐born MENA women had 2.89 times greater odds (95% CI = 1.49‐5.60) of undiagnosed ADRD compared to US‐born white women.

Conclusion

This study contributes the first national estimates of suspected undiagnosed ADRD among MENA men and women. Furthermore, our study highlights that the underdiagnosis of ADRD among MENA adults may be driven by women. Results will help to facilitate policy decisions and advocate for resources to be allocated for interventions to improve the health of this underrepresented but increasingly visible minority population.
Association between the estimated 10‐year cardiovascular mortality risk and cognitive function in older adults: results from the FINGER trial
Authors: Stephen Ruth , Hall Anette , Lehtisalo Jenni , Ngandu Tiia , Laatikainen Tiina , Rusanen Minna , Strandberg Timo , Antikainen Riitta , Tuomilehto Jaakko , Lindstrom Jaana , Peltonen Markku , Hänninen Tuomo , Soininen Hilkka , Kivipelto Miia , Barbera Mariagnese , Solomon Alina
Published: June 2023

Background

Dementia risk scores could be instrumental in the implementation of multidomain lifestyle interventions for dementia prevention. However, as relatively new tools, their performance requires further validation. Given the extensive overlap between risk factors for dementia and cardiovascular disease (CVD), multidomain interventions usually have an important vascular component and better‐established cardiovascular risk scores could become useful in this context. More evidence is needed on their ability to predict the risk of cognitive decline and dementia. SCORE/SCORE‐Older People (OP) are the official tools of the European Society of Cardiology to estimate the 10‐year CVD‐mortality risk. In this study, we investigated the association between SCORE/SCORE‐OP and cognitive function within FINGER, the first large trial showing the efficacy of a multidomain lifestyle‐ and vascular‐based intervention in preventing cognitive decline.

Method

SCORE (age<65) and SCORE‐OP (age≥65) were calculated in the population of the 2‐year FINGER trial (N = 1236, baseline and 24 months). The cognitive outcomes (baseline, 12 and 24 months) were the overall z‐score from a Neuropsychological Test Battery (NTB, 14 tests, primary outcome) and the z‐scores of the NTB cognitive domains (Memory, Executive Function, and Processing Speed, secondary outcomes). The associations between (i) SCORE/SCORE‐OP and cognition, (ii) SCORE/SCORE‐OP and changes in cognition, and (iii) changes SCORE‐OP and changes in cognition were assessed using linear mixed‐models repeated‐measures with maximum likelihood estimation.

Result

Higher baseline risk of CVD‐mortality, estimated with SCORE/SCORE‐OP, was significantly and consistently associated with worse cognition, (NTB total composite: Estimate = ‐0.036; CI: ‐0.042 to ‐0.030; P‐value>0.0001; individual NTB cognitive domains: P‐values<0.0001) and yearly lower improvement in cognitive performance (NTB total composite: Estimate = ‐0.009, CI: ‐0.011 to ‐0.007, P‐value>0.0001; individual NTB cognitive domains: P‐values<0.0001). 2‐year change in SCORE‐OP was not significantly associated with changes in cognition during the FINGER study period.

Conclusion

SCORE/SCORE‐OP could be useful in predicting the risk of cognitive decline in a trial aimed at improving lifestyle and vascular‐related risk factors of dementia. However, more evidence is needed on their efficacy in predicting dementia risk and the response to multidomain lifestyle‐ and vascular‐ based interventions. Future studies on other well‐established and easy‐access cardiovascular risk scores could also provide relevant findings.
The novel visual cognitive assessment test correlates well with plasma oligomeric amyloid beta in patients with mild cognitive impairment
Authors: Sandhu Gurveen Kaur , Zailan Fatin Zahra , Vipin Ashwati , Soo See Ann , Kumar Dilip , Ng Kok Pin , Kandiah Nagaendran
Published: June 2023

Background

Oligomeric Amyloid Beta (OAβ), is representative of a soluble, neurotoxic and pathogenic form of Aβ, which has been found to function as upstream drivers of Alzheimer’s Disease pathology (Tolar et al., 2021). It serves as a contributory factor towards the formation of cortical Aβ plaques and neurofibrillary Tau tangles, and has been found to induce oxidative stress, synaptic toxicity and neuroinflammation (Tolar et al., 2021). The pathology culminates in neuronal dysfunction/death and resultant neurodegeneration which has been found to manifest clinically as symptoms of cognitive decline. OAβ has been found to correlate with the severity of cognitive performance, as well as brain volume reduction (An et al., 2017, Wang et al., 2017, Meng et al., 2019, Youn et al., 2019, Babapour Mofrad et al., 2021). Nevertheless, its effect on language neutral cognitive tests ‐ the novel Visual Cognitive Assessment Test (VCAT) developed and validated by our team of neurologist and neuropsychologists; remains to be evaluated (Kandiah et al., 2016, Lim et al., 2018, Low et al., 2020).

Methods

A cross‐sectional pilot study was conducted in a cohort of 63 patients, clinically diagnosed with mild cognitive impairment (MCI). The patients underwent cognitive evaluation tests, Multimer Detection System (MDS) based plasma OAβ analysis and MRI based cortical grey matter evaluations (Wang et al., 2017, Youn et al., 2019, Pyun et al., 2021, Vipin et al., 2021). Pearson’s correlation evaluated associations between plasma OAβ, cognitive scores [Mini‐Mental State Examination (MMSE), VCAT] and brain volume measures [Grey Matter Volume (GMV) / Intracranial Volume (ICV)].

Results

Increasing plasma OAβ expression associated with decreasing, VCAT scores (r = ‐0.291, 95% CI = ‐0.504 to ‐0.044, p = 0.022) and MMSE scores (r = ‐0.272, 95% CI = ‐0.489 to ‐0.024, p = 0.032), in MCI patients (Figure 1A, B). Additionally increasing plasma OAβ expression also associated with decreasing and GMV/ ICV ratio (r = ‐0.264, 95% CI = ‐0.489 to ‐0.007, p = 0.045), in MCI patients (Figure 1C).

Conclusion

Findings from this study, emphasise on the promising clinical utility of plasma OAβ as a biomarker. Future longitudinal studies will validate these associations across the Alzheimer’s disease spectrum.
Simplify scales for identifying AD and MCI: A machine learning study based on six years of database
Authors: Lü Wenqi , Zhang Meiwei , Kuang Weihong , Lü Yang
Published: June 2023

Background

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by cognitive functional decline accompanied with neuropsychiatric symptoms and impairment of activities of daily living (ADL). Mild Cognitive Impairment (MCI) is considered the prodromal state of AD. Early identification of MCI is a strategy to reduce the burden of caregivers and society. Neuropsychological scales are still the most used method for identification of cognitive decline. The purpose of this study was to simplify the scales by eliminating some insensitive items based on the six years of database and machine learning methods.

Method

A total of 458 patients newly diagnosed as AD or MCI were recruited in Memory Clinic, Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University from 2014 to 2019. Neuropsychological battery was used to evaluate the cognitive function, neuropsychiatric symptoms and ADL, including Mini‐mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS), Boston Naming Test (BNT), Digit Span (DS), Auditory Verbal Learning Test (AVLT), Trail Marking Test (TMT) A and B. Alzheimer’s Disease Assessment Scale (ADAS‐cog), Clinical Dementia Rating (CDR), Instrumental Activity of Daily Living Scale (IADL), Physical Self‐Maintenance Scale (PSMS). XGboost and CART regression tree were used to test all items contained in all scales and try to explore the importance of each item. Sensitivity was reflected by the AUC (Area Under Curve).

Result

Of which 236 patients were diagnosed as AD and 222 as MCI. The mean age was 72.99±9.04 years and 51.53% were male. Among all the battery items, ADAs‐cog word recognition task showed the best importance in judging AD and MCI, followed correct numbers of AVLT delay recall, ADAs‐cog orientation, MMSE recall, TMT‐B time. The overall sensitivity for predicting AD or MCI for all items was 0.83. However, in our preliminary screening also showed the 31 items, most of which were based on the ADL scale and neuropsychiatry symptoms, contributed little to distinguishing AD from MCI. After removed these items, the sensitivity became to 0.87.

Conclusion

Cognitive assessment such as recall and orientation may be a better strategy than neuropsychiatric symptoms and ADL when identifying AD from MCI.
Single vascular insult exacerbates disease pathology in APPswe Mice.
Authors: Diwakar Latha , Hussain Rehab , Ravindranath Vijayalakshmi
Published: June 2023

Background

Vascular insults, such as microinfarcts play a major role in mixed dementia including Alzheimer’s disease (AD). Neuroimaging from longitudinal studies have shown involvement of white matter hyperintensities due to blood brain barrier (BBB) breakdown. In patients with AD the combined neurotoxic effects of amyloid‐β (Aβ) converge on brain vasculature synergistically leading to neuronal and synaptic dysfunction, which in turn leads to cognitive impairment. In the present study we examined the effect of vascular insult induced by enothelin‐1 (ET‐1, a vasoconstrictor peptide) on Aβ pathology in mouse models of AD. We further studied behavioral deficits during reduced cerebral blood flow changes and structural changes in BBB components.

Method

We injected 2µg/2μl of ET‐1 bilaterally into lateral ventricles APPswe mice carrying point mutation for APP. Behavioral assays were performed to compare associative learning and spatial memory deficits, if any after 30 days of ET‐1 injection. Immunohistochemistry for markers of endothelial cells and pericytes were done to look at the structural changes in BBB. Aβ ELISA and plaque load were tested to understand the effect of vascular insult on AD pathology.

Result

Vasoconstriction following ET‐1 injection after 30 days leads to memory deficits in AD mice while wildtype mice recovered. There were structural changes in BBB showing decreased expression of endothelial and pericyte marker, however these changes were not observed in wildtype mice. Aβ levels were increased in brain lysates of APPswe mice injected with ET‐1.

Conclusion

Single vascular insult was adequate to bring about impairment in learning and memory in APPswe mice and structural changes in BBB, which were not seen in WT type mice indicating that ET‐1 induced cerebral hypoperfusion accelerated AD pathogenesis.
Investigating ADHD and ASD features in dementia patients referred to a memory clinic in Iran
Authors: Mohammadian Fatemeh , Motamed Mahtab , Zavieh Amir , Heidari Arash
Published: June 2023

Background

Dementia is a clinical syndrome characterized by a progressive cognitive decline interfering with the function of activity of daily living in patients (1). Autism spectrum disorder (ASD) and Attention deficit hyperactivity disorder (ADHD) are two prevalent neurodevelopmental disorders affecting different brain functions manifesting mostly with impaired communication and behavior (3). These disorders initiate in childhood but usually persist into adulthood (3, 4). These disorders might overlap with dementia symptoms, as they might share common genetic and environmental backgrounds (5‐7). ASD and ADHD in dementia patients may complicate the timely diagnosis of each disorder leading to more pronounced dysfunction. Hence, this study aimed to evaluate ASD and ADHD symptoms in dementia patients referred to a memory clinic in Iran.

Method

We recruited 65 dementia patients in this study. Firstly, a cognitive neurologist diagnosed dementia’s subtypes by a precise clinical examination, cognitive assessment by applying the Montreal cognitive Assessment (MoCA). The severity of dementia was determined using the Functional Assessment Staging Tool (FAST). Consequently, we instructed the participants to fill out the autism quotient (AQ) and the Conners' Adult ADHD Rating Scales (CAARS) questionnaires for investigating their ASD and ADHD symptoms.

Result

Considering the cut‐off points of AQ and CAARS questionnaires, 18.5% of participants were diagnosed with ASD, and 35.4% were diagnosed with ADHD. Besides, we found a significant positive relationship between all subscales of CAARS and the FAST score (P < 0.05). In other words, patients with more severe dementia were more likely to have increased ADHD symptoms.

Conclusion

The results indicated that ADHD and ASD symptoms might be common manifestations in patients with dementia. This finding was in line with the previous research findings regarding the high co‐occurrence of ADHD and dementia (8). This comorbidity can further prohibit function and further worsen the prognosis. Given that there is scarce evidence on the association between ADHD and dementia in Iran, the findings of this study can pave the way for future research to elaborate more precisely on the etiological backgrounds of this association.
Micro and macro‐linguistic analysis of narrative discourse in Moroccan patients with Alzheimer’s Disease
Authors: Taiebine Mohamed , Faris Mustapha El Alaoui
Published: June 2023

Background

The production of narrative discourse or connected speech implies dynamic and complex functions at different levels of neuro‐cognitive, micro (parts of speech) and macro‐linguistic processing (cohesion and coherence). Such functions are classically impaired in Alzheimer’s disease (AD). Several studies have described these impairments in European languages; however, no study has characterized them in terms of neuro‐psycholinguistic patterns in Arabic.

Method

We studied the speech sample of six patients with moderate Alzheimer’s disease from the Alzheimer’s Center in Rabat. They described orally the picture of cookies theft subtest (BDAE). They meet the clinical criteria for AD (McKhann, 2011). The average age is 69 years (SD: 5.9; 61‐77) and of education is 13.6 years (SD: 2.3; 9‐15), duration of the disease is 5 years (SD 2.09; 3‐8). The neuropsychological assessment has been carried out with MoCA (Montréal Cognitive Assessment), MIS (Memory Impairment screen), Fluency tasks and Clock drawing test. Regarding discourse analysis and psycholinguistic variables, we used the method which has been described by Croisile (1996) and Boschi et al (2017).

Result

The neurolinguistic assessment showed an impairment of macro‐linguistic variables. The effectiveness of speech was clearly one of the most impaired variables as well as the syntactic complexity in the majority of patients. Cohesion has been lower than local and global coherence. These macro‐linguistic performances revealed a pragmatic dysfunction as part of the neuropsycho‐linguistic profile of our patients depending on their disease duration. However, at a micro‐linguistic level, functional words and verbs were the most produced in oral description compared to nouns, adjectives and adverbs. Such results might evoke the hypothesis of an impairment of explicit linguistic knowledge which involved different intra and inter‐linguistic systems in AD.

Conclusion

The wide range of cognitive‐linguistic impairments which has been highlighted during the cookie theft picture description, showed the importance of assessing micro and macro‐linguistic impairments in narrative speech in Moroccan patients with AD. Such linguistic task is an added‐value to formal assessments and follow‐up of cognitive decline in AD.
Brazilian version of Northwestern university famous faces test (NUFFACE‐Br): Evidence of validity between control and clinical groups
Authors: Proença Mirela Silva , da Silva Filho Silvio R. B. , Moriguti Julio , Tumas Vitor , Foss Maria Paula
Published: June 2023

Background

NUFFACE was created to identify the locus of name‐face failure common in healthy aging and dementia. Psychometric studies are necessary for the development of the Brazilian version. Therefore, we intend to verify the evidence of predictive (or diagnostic) validity of this instrument.

Methods

a total 24 participants were included in this study and divided into 12 cognitively healthy elderly (NC) and 12 with dementia due to Alzheimer’s Disease (AD; CDR‐1). All responded to the NUFFACE‐Br, which has four tasks: 1) facial naming; 2) verbal description of the facts related to the face; 3) verbal description in response to the printed name; and 4) face‐name matching (multiple‐choice format). Different types of errors, such as Semantically Related (SR), Semantically Unrelated (SU), Phonological Similarity (Ph), “I don’t know” (DK), and Others (O), were developed as part of the correction criteria. The comparison of sociodemographic variables and NUFFACE‐Br total tasks were performed by Mann‐Whitney U test, adopting a significance level of 5%.

Results

The groups did not differ by age, education, and sex (p<0.05). The NC performed better than the AD in almost all tasks of this instrument (p<0.01), except for task 4 (p<0.266). The AD presented more difficulty in the naming faces tasks (average = 14±6.6) than the others and similar performance to the NC in the face‐name correspondence (average score = 30.7±2.1). A higher frequency of all types of errors was verified in the AD group for the first three tasks of this instrument, except for the “phonological similarity,” in which the frequency of errors was the same between the groups. Task 4 presented a higher frequency in SR, SU, and O errors.

Conclusion

Significant differences were verified between the NC and AD groups, indicating the predictive (or diagnostic) evidence of NUFFACE‐Br. The face‐name matching task was the only one that did not show differences between the groups. The AD presented a higher frequency of errors when compared to the NC, especially in the task of naming faces. Further psychometric studies are being conducted to elucidate the clinical evidence of this instrument to old Brazilian adults.