bluuebunny/crossref_metadata_2025 huggingface dataset:
The association of physical activity and cognitive decline has become important with the increase in dementia prevalence. These systematic review and meta‐analysis of longitudinal studies demonstrate that association
Authors: Eissa Elissa Abou
Published: June 2023

Background

Dementia is increasing in prevalence across our globally ageing population. In absence of disease modifying therapy, the need to assess the effectiveness of preventative measures becomes important. It is becoming clear that intervention before disease manifests is crucial. Physical activity (PA) is the most influential risk factor for dementia, examining impact on cognitive decline is important to discern.

Method

Our search criteria involved conducting a database search through MEDLINE (Ovid) as well as examining two prior reviews, with protocol registered with PROSPERO (registration number: CRD42019129449). Longitudinal studies on population ≥18 years of age with cognition measured at both baseline and follow‐up were included. Included studies were assessed for their methodological quality.

Result

Overall, 42 studies were included, with literature showing evidence of an association between increase PA and reduced cognitive decline. Components of PA were reported on as follows: frequency in 37 studies, intensity in 28 studies, duration in 25 studies, and type in 22 studies. Meta‐analysis showed PA of greater frequency and duration, and more vigorous intensity, was significantly associated with reduced cognitive decline (relative risk 0.72, 95% confidence interval 0.62, 0.82; p<0.001).

Conclusion

Data available to date suggests that a wide range of different types of activity may be important on influencing preventive impact. In addition frequency, duration and intensity of PA are each significantly associated with reduced cognitive decline where greater frequency and duration of PA are associated with reduced cognitive decline, as is increased average intensity. PA recommendations are required to increase adherence in order to delay the onset of cognitive decline. It is important that future studies examine these details as this review revealed a paucity of research on key components to guide adherence to recommendations.
Trail Making for electronic touchscreen self‐administration (eTrails) as used in the remote iPACES neuro‐exergaming trial for Mild Cognitive Impairment (MCI): An initial validation report
Authors: Roque Nelson A , Ferguson Irelee , Saulnier Emilie T , Anderson‐Hanley Cay
Published: June 2023

Background

To enable brief and integrated serial assessment across a national sample, we developed an electronic version of the Trail Making test (eTrails) for remote self‐administration on digital devices. eTrails, a digital, web‐based assessment, mimicking the traditional paper version of Trails B (see demo: https://bit.ly/33DCPGP), in which participants draw a line from a number to a letter in alternating, ascending order, was integrated into the iPACES app. Herein we report on initial validation of eTrails, as compared with the paper Trail Making Test.

Method

This initial validation report examined digital trail making data (n = 34 sessions) serially collected from ten MCI and caregiver participants in the iPACES v3 clinical trial (mean age = 70.2, mean years of education = 16.9). Included in analyses were eTrails data for traditional metrics (i.e., overall completion time) and novel digital biomarkers extracted from event‐level data (e.g., # of lifts and pause time). After a baseline tele‐neuropsychological evaluation in which paper Trail Making was administered (Forms A&B), at predetermined study intervals (typically weekly), participants were automatically prompted to complete the eTrails on their iPACES tablet. In the eTrails, participants were presented with one of four randomly selected alternate forms of trail making stimuli (i.e., different spatial configurations of Form B).

Result

Overall completion time from eTrails was moderately correlated with both forms of paper‐based trail making completed at baseline (correlation with Paper Trails A: r = .37, p = .030; correlation with Paper Trails B: r = .41, p = .017). Novel digital biomarkers (i.e., # lifts, pause time) were moderately correlated (r’s = 0.59‐0.6, p’s < .001) with the traditional scoring of the eTrails (i.e., assessment completion time in seconds), and though non‐significant, weakly correlated with completion time of paper Trails A (r = 0.20, p = 0.25).

Conclusion

These preliminary data provide initial evidence of validity, that eTrails as a serial assessment of subtle cognitive decline can serve as a remote self‐administered digital test for serial assessment of executive function and will be further evaluated in our ongoing iPACES study. Future research may explore the sensitivity of novel digital biomarkers extractable from event‐level data.
Stroop for electronic touchscreen self‐administration (eStroop) as used in the remote iPACES neuro‐exergaming trial for Mild Cognitive Impairment (MCI): An initial validation report
Authors: Roque Nelson A , Ferguson Irelee , Saulnier Emilie T , Anderson‐Hanley Cay
Published: June 2023

Background

In collaboration with the Mobile Monitoring of Cognitive Change (M2C2; 1‐U2C‐AG060408‐01) Project, our team developed a tablet‐based electronic Stroop (eStroop) task. Initial development explored direct translation of the paper‐Stroop (pStroop) often used in clinical settings, and found that this resulted in ceiling effects. Herein we report on initial validation of the eStroop task from the iPACES v3 clinical trial.

Method

Initial validation examined eStroop data (n = 59 sessions) serially collected from ten MCI and caregiver participants in the iPACES v3 clinical trial (mean age = 70.2, mean years of education = 16.9). Included in analyses were eStroop data for both traditional metrics (i.e., overall accuracy by block condition), response time, as well as typically constructed difference/ratio scores (i.e., AC ratio). After a baseline tele‐neuropsychological evaluation in which paper Stroop was administered, at predetermined study intervals (typically weekly), participants were automatically prompted to complete the eStroop on their iPACES Android tablet. In the eStroop, participants were presented with four blocks of 40 trials: (1) color words in black font, (2) congruent word and font color; (3) incongruent words with font color; (4) mixed congruent and incongruent trials.

Result

The paper Stroop AC Ratio (total seconds to complete paper A, divided by time to complete paper C), was moderately negatively correlated (r = ‐0.52, p < .001) with average response time on block three of eStroop (incongruent words with font color). The pStroop AC Ratio was also significantly negatively correlated with number of errors on block one (r = ‐0.42, p < .001), two (r = ‐0.26, p = 0.04), three (r = ‐0.39, p = 0.002), and four (r = ‐0.26, p = .049). A weak, significant positive correlation (r = 0.44, p < .001) was observed between the AC ratio from pStroop and eStroop. Very weak non‐significant correlations between paper Stroop AC Ratio and average response time on blocks one, two, and four of eStroop were observed.

Conclusion

These pilot data provide preliminary evidence that the eStroop can serve as a remotely and self‐administered digital test for serial assessment of executive function and will be further evaluated in our current iPACES study.
Prevalence of anti‐egg albumin antibodies in cerebrospinal fluid of patients with mild and severe Alzheimer’s Disease. Correlation with gender and incidence of anti‐casein antibodies and AGEs.
Authors: Amanatidou Dionysia , Tsolaki Magda , Fili Maria , Anastasiou Anna , Papageorgiou Athanasia , Bourmas George‐Marios , Eleftheriou Phaedra
Published: June 2023

Background

Alzheimer’s Disease (A.D.) is a multifactorial process. Advanced glycation end products (AGEs) have been correlated with disease development1. Additionally, high concentrations of antibodies against the food derived antigens egg‐albumin and bovine casein, have been detected in patients with Alzheimer’s disease in preliminary research presented by our team, previously (AAIC 2018).

In the present study, antibodies against egg‐albumin and bovine casein as well as AGEs were detected in the cerebrospinal fluid of 36 patients with mild and 35 patients with severe Alzheimer’s Disease and 13 healthy individuals and a correlation between the measured parameters and sample properties was attempted.

Method

ELISA plates pre‐treated with highly hydrophilic microlon resin were used for the purpose of this study2. Egg‐albumin or bovine casein antigens were attached at the ELISA plates for the measurement of antibodies. Additionally, polyclonal antibodies against multiple AGE products were used to detect attached sample CSF AGEs.

Result

According to the results, 48,6% of of the samples of patients with severe AD had anti‐egg albumin concentration higher than mean concentration of healthy idividuals+2SD (characterized as positive) compared to 8.3% of positive samples in patients with mild disease. An overall 265% increase in mean concentration was observed in severe compared to mild patients, indicating association with severity. The observed difference was significant at p = 0.01 according to mann witney U test. Lower anti‐egg albumin concentrations were observed in female samples of either mild or severe disease (Figure 1). Much lower incidence of anti‐casein antibody positive samples was found in in severe AD (5.7% positive in severe versus 0% in mild AD). A slight, not statisticaly significant, increase in mean anti‐casein antibodies concentration (23.7%) and AGEs (16.2%) was observed in severe compared to mild disease with the higher concentrations also detected in the most positive to anti‐egg albumin samples.

Conclusion

The results indicated a potential correlation of antibodies against egg‐albumin with the severity of Alzheimer’s disease with increased incidence in male patients. A lower correlation was observed in case of anti‐casein antibodies and AGEs.

References:

1. Takeuchi et al., Current Pharmaceutical Design, 14(10), 2008, 973‐978.

2. P. Eleftheriou, etal. Biomed. Res. Int., 2014.
The niacin receptor HCAR2 induces a protective response of microglia to amyloid pathology.
Authors: Moutinho Miguel , Puntambekar Shweta S , Tsai Andy Po‐Yi , Coronel Isarel , Lin Peter Bor‐Chian , Casali Brad T , Martínez Pablo , Oblak Adrian L , Reeves Cristian A Lasagna , Lamb Bruce T , Landreth Gary E
Published: June 2023

Background

Dietary intake of niacin correlates with reduced risk of Alzheimer´s disease (AD). Niacin is a ligand for the niacin receptor HCAR2, which, in the brain, is expressed by microglia. HCAR2 ligands have been shown to modulate microglia functions and exert neuroprotective effects in different models of neuronal injury. Therefore, we hypothesized that HCAR2 modulates a protective microglial phenotype in AD, which can be stimulated by HCAR2 agonists.

Method

To assess the role of HCAR2 in amyloid pathology, the brains of the AD animal model 5xFAD and 5xFAD mice lacking Hcar2 gene (5xFAD‐KO) were subjected to transcriptomic, immunohistochemistry and biochemical analysis. Furthermore, to activate HCAR2, 5 month‐old 5xFAD mice were treated with a FDA‐approved formulation of niacin (Niaspan®) daily, by oral gavage for 30 days with 100 mg niacin/kg. Treated animals were sacrificed and the brains were collected for immunohistochemistry and biochemical analysis. To validate that Niaspan® effects were dependent on HCAR2, we performed the same treatment paradigm and analysis using 5xFAD‐KO mice.

Result

Our results indicate that microglia significantly induce HCAR2 expression in the AD brain. Lack of Hcar2 in the 5xFAD mice leads to a deficient response of microglia to amyloid pathology, which is accompanied by an increase in plaque load and exacerbation of the amyloid‐associated neuropathology. Niaspan® treatment increased the response of microglia to amyloid pathology, decreased plaque burden in 5xFAD, and exerted a neuroprotective effect evidenced by reduced neuronal loss in the subiculum, accompanied by a rescue of working memory deficits. Niaspan® did not induce these beneficial effects in 5xFAD‐KO mice.

Conclusion

These data suggest that HCAR2 induces a protective microglial phenotype in AD. Furthermore, activation of HCAR2 by Niaspan® treatment has neuroprotective effects in AD, even after the onset of severe amyloid pathology, possibly through the stimulation of a protective microglia response. Niaspan® is a FDA‐approved drug, thus there is a translational potential of this strategy into clinical practice, supporting further study of this therapeutic approach.
Music as a trigger for specific memories
Authors: Pillay Jayendran
Published: June 2023

Background

This study uses the expertise of an ethnomusicologist who uses preexisting music in the brain music as the cue to trigger the autobiographical memories of her own mother struggling with dementia.

Method

By adapting a methodology in Ethnomusicology involving the autobiography of one’s music history, I set up the experiment for another ethnomusicologist to conduct. Dividing the study into discrete music time periods (infancy, childhood, teenager, young adult, older adult), I delineated specific songs or pieces of music with powerful meanings to the patient in those time periods to be played. The responses of the patient on video was then recorded.

Result

Each of those pieces of music had some level of recognition by the Alzheimer’s patient, some stronger than others. Other attendant contextual memories surfaced during the experiment, suggesting autobiographical recall, despite a weakened sense of time and space after the onset of Alzheimer’s.

Conclusion

This single case study needs to be broadened into a larger scale experiment involving many participants to assess the efficacy of this ethnomusicological‐derived approach to improve autobiographical recall abilities among the Alzheimer’s patients. This approach also makes it possible for families to engage in the autobiographical recall process using the preexisting music in the patients’ neural pathways. This study also offers collaborative efforts between Ethnomusicology and Neurology in running clinical trials to develop autobiographical memory recall processes for therapy.
TREM2‐H157Y Increases Soluble TREM2 Production and Reduces Amyloid Pathology
Authors: Qiao Wenhui
Published: June 2023

Background

The p.H157Y variant of TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) has been reported to increase Alzheimer’s disease (AD) risk. This mutation in the extracellular domain of TREM2 localizes at the cleavage site and was shown to enhance shedding and impair phagocytosis in vitro by ectopic expression of TREM2‐H157Y in HEK293 cells. However, the physiological and AD‐related outcomes of TREM2 H157Y mutation in vivo remain unknown.

Method

We generated a novel Trem2 H157Y knock‐in mouse model through CRISPR‐Cas9 technology and investigated how Trem2 H157Y mutation impacts TREM2 proteolytic processing, synaptic function, and AD‐related amyloid pathology by conducting biochemical assays, immunofluorescent staining, hippocampal electrophysiology, and in vivo micro‐dialysis in awake, free‐moving animals.

Result

Consistent with previous in vitro findings, TREM2‐H157Y increases the amount of soluble TREM2 (sTREM2) in the cortex and serum of mutant mice compared to the wild type controls. Interestingly, the Trem2 H157Y variant enhances synaptic plasticity without affecting microglial density and morphology. In the presence of amyloid pathology, TREM2‐H157Y surprisingly accelerates Aβ clearance and reduces amyloid burden and microgliosis.

Conclusion

Taken together, our findings support a beneficial effect of the Trem2 H157Y mutation in synaptic function and in mitigating amyloid pathology. Considering the genetic association of TREM2 p.H157Y with AD, we speculate TREM2‐H157Y might increase AD risk through an amyloid‐independent pathway, as such its effects on tauopathy and neurodegeneration merit further investigation.
The role of FUT8‐catalyzed core fucosylation in Alzheimer’s amyloid‐β oligomer‐induced activation of human microglia
Authors: Jin Lee‐Way , Lucente Jacopo Di , Schindler Ryan , Tena Jennyfer , Mendiola Ulises R , Tang Xinyu , Zivkovic Angela M. , Lebrilla Carlito B. , Maezawa Izumi
Published: June 2023

Background

A previous RNA‐seq study of human Alzheimer’s disease (AD) brain samples revealed significant upregulation of FUT8 coding for α1‐6 fucosyltransferase in parahippocampal gyrus, suggesting a role of FUT8 and the core fucosylation it catalyzes in early AD. Despite the well‐recognized roles of core fucosylation in immune regulation, its significance in microglial function, especially in neurodegenerative conditions such as AD, has rarely been studied.

Method

Human microglia derived from induced pluripotent stem cells (iMG) were used as the model system. To simulate microglia in the early stage of AD, we stimulated iMG derived from a subject of APOE3/3 genotype with amyloid‐β oligomer (AβO, 3 μM). The degree of microglia activation was determined by cytokine induction and MAPK phosphorylation. Lectins were used in flow cytometry, cytochemical staining, and lectin blotting to determine the changes in core fucosylation. Fucosylation was also examined by MS/MS‐based N‐glycan analysis. FUT8 expression in brain or cell samples was determined by quantitative PCR and Western blotting. FUT8 inhibition was induced by siRNA‐mediated gene silencing. The transcriptional regulation of FUT8 was investigated by ChIP‐PCR using p53 antibodies.

Result

Human iMG responded to AβO with a pattern of pro‐inflammatory activation within 24 hours. Using two lectins specifically recognizing α1,6 core fucose, AAL and LCA, in flow cytometry and fluorescence staining, we showed that such an activation was associated with increased core fucosylation. This observation will be further verified by N‐glycomic analysis. Inhibition of fucosylation by two inhibitors, 2FF and 6‐Alk‐Fuc, as well as FUT8 knockdown by specific siRNAs suppressed AβO‐induced iMG activation. AβO‐activated iMG also showed increased protein levels of FUT8 and p53. Because p53 was previously shown to be a direct transcriptional activator of FUT8 in tumor cells, we will test whether p53 is responsible for FUT8 upregulation by ChIP‐PCR. The in vivo relevance of our results is supported by qPCR results showing increased levels of FUT8 transcript in human temporal cortex, 5xFAD mouse cortex, and microglia isolated from 5xFAD mice.

Conclusion

Our data suggests that FUT8‐catalyzed α1‐6 core fucosylation is required for AβO‐induced microglia activation and may play a role in the pathogenesis of AD.
The decline of verbal memory after stroke is associated with decreased functional connectivity of hippocampal subregions
Authors: Li Rui , Khlif Mohamed Salah , Egorova Natalia , Restrepo Carolina , Ebaid Deena , Brodtmann Amy
Published: June 2023

Background

The hippocampus plays an important role in learning and integrating events to form episodic memory. Many ischemic stroke survivors experience memory impairments, and some report decline in memory function. We examined changes in functional connectivity (FC) of the hippocampus and its subregions in stroke survivors over 3 years compared to age‐matched stroke‐free healthy controls (HC), and the associations between hippocampal FC and verbal memory performance.

Method

Participants from the Cognition And Neocortical Volume After Stroke Study were analysed at 3‐months, 1‐year and 3‐years post‐stroke. Verbal memory performance at each timepoint was evaluated with delayed recall of the Hopkins Verbal Learning Test‐Revised that was standardized using appropriate age stratified normative data. Evaluable resting‐state functional magnetic resonance imaging sequences were compared with age‐matched healthy controls (see Table 1 for demographics) following pre‐processing. The hippocampus was parcellated into whole hippocampus and four subregions (body, head‐medial, head‐lateral and tail) and bilateral seed‐based FC analyses were conducted for each region using CONN toolbox (V20.b). Longitudinal changes of FC between two timepoints were computed by the direct subtraction.

Result

Groups were age‐ and sex‐matched but HC had significantly greater years of education (see Table 1). Greater FC change was seen in stroke survivors between 3‐months to 1‐year in left hippocampal head‐medial (right lateral occipital; p‐FDR = 0.012) with years of education adjusted. Stroke patients displayed significant decline in verbal memory between the 1‐ and 3‐year timepoints. Significantly decreased FC of left hippocampal head‐medial (precuneus; p‐FDR = 0.011) correlated with verbal memory decline between 3‐months and 3 years after adjusting years of education and gender. There was no significant decline or change of verbal memory observed in HC, and the correlated hippocampal FC changes were not present in HC group either.

Conclusion

Change in left hippocampal subregional FC is different in stroke survivors compared to HC. Subregional hippocampal FC changes correlate with verbal memory decline. Subfield FC analyses may shed new light into mechanisms of post‐stroke memory impairment.
The “COGS CLUB” : A psychosocial intervention for people with Alzhiemer’s disease
Authors: Fabbo Andrea , Bevilacqua Petra , Garzetta Glenda , Zavatta Elenza , Bergamini Lucia
Published: June 2023

Background

The “Cogs Club” is a multi‐modal intervention based on the Cognitive Stimulation Therapy (CST, Spector A.).CST is cost‐effective for people with mild‐to‐moderate dementia and is recommended in the UK by NICE. CST, in our adaptative model, is related to other psycho‐social activities (OT, music, physical activity). Cogs Club changes a traditional session of about an hour into 4 hours of activities.Objectives: the aim of this study is to verify the efficacy of this muldimodal psychosocial intervention

Method

the project is promoted by the local Alzhemer’s associations situated in Modena (Italy) and conducted by 3 professionals (a psychologist, an OT and a fisioterapist) who provide scheduled interventions ad : cognitive stimulation therapy (CST), occupational therapy and physical activities with music. Partecipants who took part in the study (n° 26 people with mild‐ moderate Alzheimer’s dementia, M9: F17, mean age 78.23 ±5.11 years, education: 7.2 ± 3.86 years) were submitted at T0 (basal evaluation) and T1 (after 3 months) to an assessment composed by ACE‐R, GDS‐15, DAD, QoL‐AD and ZBI. People with sensorial deficit, motor or behaviour disorder was excluded.

Result

at T1 all indicators (cognitive: MMSE 22,6 vs 23,4, p 0,096; ACE – R 63,54 vs 65,96 p 0,066; functional: DAD 0,68 vs 0,69, p 0,103; emotional‐affective : GDS 5,35 vs 4,12 p 0,039 and quality of life : QoL AD pz 31,5 vs 33,38, p 0.129; Qol AD cg: 29,04 vs 30,96, p 0,459) of the PWD have improved even if only the depression is of clinical relevance. Regarding the caregiver we found an improvement in their quality of life even with an increase in perceived care stress (Zarit 34,09 vs 36,65, p 0,098).

Conclusion

the purpose of the project is also to create a context for the socialisation and a net of formal and informal connection to people with mild‐ moderate dementia who traditionally don’t ask to access health services. The main goal is to delay as much as possible the development of the disability but further studies are necessary to encourage this preliminary results.
Relating attention related activities of daily living with cognitive performance on attentional network task in patients with Dementia of Alzheimer’s Type
Authors: Rai Pooja , Singh Indramani L. , Singh Tara , Tiwari Trayambak , Joshi Deepika
Published: June 2023

Background

Attentional functioning plays a crucial role in task performance in the daily facets of life, and impairments in attention are present in a multitude of psychiatric disorders such as Alzheimer’s, Parkinson’s, stroke, and schizophrenia. The assessment of attention has been achieved by Attention Network Test (ANT) in various research which is a computerized testing measure that was developed to measure these three networks of attention viz. alerting, orienting and executive control.

Method

The attentional network task consists of alerting, orienting and executive control. In the present study the relationship between performance on attention network system and activities of daily living was analyzed on 15 mild dementia of Alzheimer’s type. The activities of daily living has been measured through Everyday Activities Scale in India (EASI). Further, correlation has been calculated in alerting, orienting and executive control and scores on EASI.

Result

The result found that alerting has been significantly positive correlated with items on EASI related to understand events, deliver message. The orienting network has been significantly positive correlated with items on EASI related to toilet location, shirt buttoned, lose way in village. The executive control network is significantly positive correlated with items on EASI related to complete task, dress properly.

Conclusion

The result showed a relation between attention network and activities of daily living which showed that attention is the prerequisites for various of the daily functioning.
PROTECT Norge: Online assessment of potentially modifiable risk factors for dementia on cognitive performance in a Norwegian ageing cohort
Authors: Testad Ingelin , Aakre Jon Arild , Ushakova Anastasia , Corbett Anne , Gjestsen Martha Therese , Aarsland Dag , Ballard Clive G
Published: June 2023

Background

PROTECT Norge, a fully digital platform, aims to help determine the role of defined genetic, lifestyle and environmental factors on cognition, health and wellbeing in people 50+. Annual questionnaires on demographics, medical conditions and medication use, mental health and lifestyle are completed online. The current study aims to assess whether potentially modifiable risk factors for dementia as presented by the Lancet Commission by Livingston and colleagues (2020) are related to cognitive performance in cognitively healthy people aged 50 and above.

Method

A total of 2349 participants completed the PROTECT Cognitive Test System, an online cognitive battery containing six tasks which assess visual episodic memory, spatial and working memory, verbal reasoning, visual attention and task switching. The following risk factors were included in our analysis: physical activity, alcohol use, smoking, social isolation, age, BMI, education, depression, high blood pressure, head trauma and hearing loss. Multiple hierarchical regression analysis was performed. Separate analyses were conducted with the average performance across three sessions for each of the six cognitive measures as the dependent variable. Independent variables were included into the model in a hierarchy based on known risk factors for dementia.

Result

Results show that age was associated with reduced cognitive performance for all tasks (p<0.001). In addition, for the digit span test, the risk factors were found to influence the test score were: smoking and previously diagnosed stroke. For the paired associate learning task, the only additional significant risk factor appeared to be gender, with male gender associated with poorer performance. For the grammatical reasoning task, the risk factors associated with lower scores were lower education, older age and smoking. For the switching Stroop test, the risk factors of lower scores were older age, smoking and previously diagnosed depression. For Trail‐making B test, the risk factors of lower scores were age, stroke and the history of heart disease.

Conclusion

These preliminary results may improve our understanding of potentially modifiable risk factors for dementia and could inform the design and delivery of interventional trials as a mean to protect cognition in later life and to prevent or slow progression of cognitive decline.
A literature review on the beneficial effects of music on aging auditory cortex and memory
Authors: Alatta Lina , Elomeiri Leina , Mohamed Suzan , Joda Malaz , Elsayed Sarah , Patel Krupa , Elshaikh Abeer , Dahab Lubaba , Ibrahim Mohammed B. , Obeid Tamadur , Abdelrahman Nadir G
Published: June 2023

Background

Recent studies examining the impact of music on long‐ and short‐term memory, as well as cognitive function, have emerged with contradictory findings. This study investigates the positive impact of music on memory and the auditory cortex in people of all ages.

Method

In the PubMed database, we searched for studies that have examined the impact of music on memory and auditory function. From January 2011 to June 2021, we searched for studies on the adult population that were “clinical trials, case control cohort and cross‐sectional studies, systematic reviews and meta analyses” in English. In our search, we used a combination of the keywords “Music, Aging, Memory, Auditory Cortex.” Four reviewers independently extracted and assessed the studies based on predetermined criteria. To eliminate bias, the results were double‐checked by six people (fellows, researchers, etc.).

Result

We chose eight studies from a total of 108. Two studies linked music exposure to improved executive function in the aging brain, four studies examined the correlation between music exposure and improved auditory memory, one study compared the aging brains of musicians and non‐musicians, and two studies pointed at music in dementia and Alzheimer’s patients. The total number of participants in the study was 409, with an average age of 54 years and a range of 17 to 91 years. The duration of exposure to music varies between less than five and eleven years, with an average of eight and a half years. The primary finding is that music has a positive influence on aging brains' auditory cortex, memory, and executive skills. The impact of music on specific parts of the aging brain is a secondary outcome.

Conclusion

Music has a positive influence on the auditory cortex, memory, and several brain executive functions, according to our findings. Adults should participate in music‐related activities to promote a healthy auditory cortex and memory aging. The absence of prior research on this topic was one of the study’s limitations. More research is needed to better understand the impact of music on the aging brain.
The Total CES‐D score from the 14‐item version as a predictor of cognitive decline
Authors: Zinkunegi Ainara Jauregi , Koscik Rebecca Langhough , Johnson Sterling C. , Mueller Kimberly D , Bruno Davide
Published: June 2023

Background

Depressive symptomatology is associated with cognitive decline and greater risk for dementia. Studies have examined this association using self‐report measures such as the Centre for Epidemiologic Studies‐Depression Scale (CES‐D; Radloff, 1991). Although the CES‐D was originally designed as a 20‐item scale, certain items have been reported to misrepresent depressive symptoms due to sex and cultural differences, which are addressed in the 14‐item version of this measure (Carleton et al., 2013). The aim of this study was to examine how the CES‐D total score from the 14‐item version compared to the 20‐item version in predicting progression to cognitive decline from a cognitively unimpaired baseline, across genders.

Method

Data were extracted from the Wisconsin Registry for Alzheimer’s Prevention. A total of 1,055 participants were included who were cognitively unimpaired and stable at baseline and had at least one follow‐up assessment. Bivariate logistic regression analyses were conducted using follow‐up consensus diagnosis as outcome (cognitively unimpaired stable vs. cognitive unimpaired declining, mild cognitive impairment or dementia); baseline total CES‐D scores from either the 14‐item or 20‐item version were used as predictors in separate analyses; age at last follow‐up assessment, age difference between baseline and last follow‐up assessment, years of education, and polygenic risk score were covariates (see Table 1).

Result

In female participants, we observed that the logistic regression model with the total CES‐D score from the 14‐item version was statistically significant (χ2(5) = 54.674, p = .001) and explained 15.2% (Nagelkerke R2) of the variance in predicting cognitive decline; this result was comparable to that with the 20‐item version, which was also statistically significant (χ2(5) = 53.276, p = .001) and explained 14.8% of the variance. In male participants, the model with the total score from the 14‐item version was statistically significant (χ2(5) = 14.846, p = .011) and explained 9.9% of the variance, whereas the model with the total score from the 20‐item version was statistically significant (χ2(5) = 14.070, p = .015) and explained 9.4% of the variance.

Conclusion

Our findings suggest that the total CES‐D score from the 14‐item version is comparable to, if not slightly better than, the score from the 20‐item version in predicting progression to a clinical level of cognitive decline in both males and females.
Plasma levels of soluble ADAM10 are increased in persons with Alzheimer’s disease and Mild Cognitive Impairment
Authors: Grigoli Marina Mantellatto , Manzine Patricia Regina , Cominetti Marcia Regina
Published: June 2023

Background

Active ADAM10 is a transmembrane protein with α‐secretase function that inhibits β‐amyloid (Aβ) peptide formation, an important neuropathological agent of Alzheimer’s disease (AD). In addition, persons with cognitive decline, such as Mild Cognitive Impairment (MCI), have a high conversion rate to AD. Previous studies show that the levels of active platelet ADAM10 are reduced in persons with AD dementia, compared with cognitively healthy individuals. In blood plasma the inactive and soluble form of ADAM10 is found. In this study we investigated the levels of inactive ADAM10 in plasma in order to corroborate with previous results found in platelets.

Method

This study was approved by the UFSCar’s Research Ethics Committee (CAAE: 02763012.0.0000.5504). Altogether, samples from 88 participants (n = 28 MCI, n = 31 AD and n = 29 controls) were analysed in this study. Blood samples were collected, plasma was separated and total protein content (15µg) was run on gel electrophoresis (SDS‐PAGE). Soluble ADAM10 (50‐55kDa) was identified by western blotting, using the anti‐ADAM10 antibody (Abcam, Ab39180) followed by the secondary antibody (Abcam, Ab97051). The serum albumin protein (66kDa) and a “young control” performed with plasma samples from a young donnor were used as endogen controls to avoid interassay biases in the densitometry analyses. Bands were measured by volume adjusted in Image Lab software and statistical analysis were performed in GraphPad Prism software.

Result

Plasma levels of soluble ADAM10 are increased in persons with MCI (p = 0.0325) and AD (p = 0.0129), compared with cognitively healthy older adults.

Conclusion

Plasma‐soluble ADAM10 has potential as a biomarker molecule for AD. Analyses in plasma are advantageous as they represent an easily accessible and low‐cost tool that can be used in the future by health services to aid in the early diagnosis of AD.
Cognitive function and hearing loss: A longitudinal investigation of the effect of hearing aid use on cognitive performance in older adults
Authors: Sarant Julia Z , Harris David , Maruff Paul , Schembri Adrian , Busby Peter , Phillips Jocelyn , Nixon Grace , Davine Ella , Anderson Charlotte
Published: June 2023

Background

Hearing loss is highly prevalent in older adults and has been identified as the largest single potentially modifiable risk factor for dementia. Although hearing aids are a successful treatment for hearing loss, it is unknown whether their use can delay the onset of cognitive decline or improve cognitive function. Less than 20% of adults who would benefit from hearing aids actually using them. Results at 18‐ and 36‐months post‐hearing aid fitting in this prospective Australian longitudinal study will be presented.

Method

Participants were assessed before and every 18 months after hearing aid fitting. Results were compared with those of a control group of participants of a cohort study of aging in older adults (AIBL) and also with a large normative group using the cognitive assessment tool. Assessments included cognitive function (visually presented computerized assessment battery), hearing, speech perception, quality of life, activity, diet, loneliness and isolation, anxiety, depression, medical health, and genetic risk

Result

After 18 months of hearing aid use there was no significant cognitive decline for hearing aid participants, and group mean scores for executive function significantly improved, with stability or improvement for 92%. Comparative group results showed no improvement at 18 months. At 36‐month follow‐up, after almost 18 months of repeated COVID lockdowns, hearing aid use had decreased, and loneliness had increased. The previously observed improvement in executive function was no longer evident, but performance on 4/5 subtests remained stable.

Conclusion

This is the first study to follow participants for this length of time. After 36 months of hearing aid use, most participants had remained stable, and a subset had improved cognitive function. These results suggest that hearing aid use may not only delay cognitive decline but could improve cognitive function. This study will continue to investigate whether cognitive function could continue to improve for some participants, and the longer‐term trajectory of effects of hearing aid use.
Visual mental imagery in Lewy Body Dementia patients with visual hallucinations: preliminary results
Authors: D'Antonio Fabrizia , Vita Antonella Di , Margiotta Roberta , Panigutti Massimiliano , Boccia Maddalena , Sepe‐Monti Micaela , Canevelli Marco , Ferracuti Stefano , de Lena Carlo , Guariglia Cecilia , Bruno Giuseppe
Published: June 2023

Background

Lewy body dementia (LBD) is characterized by the presence of visual hallucinations (VH), however mechanisms underpinning these phenomena are still unknown. Visual mental imagery (VMI) is defined as the ability to see with the mind’s eye, in the absence of adequate sensory input (Kosslyn, 1987). Hallucinations are defined as percepts in the absence of an appropriate stimulus from the external world. Both visual mental images and VH consist of a “stimulus‐independent” image production, however the association between VH and VMI has not yet been investigated in LBD. The aim of the study was to investigate VMI processes in patients LBD with VH.

Method

Nineteen LBD patients (mean age = 75.4, SD = 6.9; mean education = 10.2, SD = 4) attending the “Sapienza” University Hospital in Rome and 13 Healthy controls (HC) (mean age = 71.9,DS = 7.9; mean education = 12.8, SD = 4.9) matched for age and education were enrolled. VMI was assessed in patients and HC by means of an adapted version of The Complete Visual Mental Imagery Battery (CVMIB; Palermo et al., 2016), including tasks probing the generation of different visual mental images (i.e. object; building and face), maintenance, inspection and transformation processes, and through the O’Clock test (Grossi et al.,1994) including a perceptual and imaginative tasks.

Result

Non‐parametric analyses revealed that LBD performed worse than HC in all CVMIB tasks. Furthermore LBD performed worse than HC in both O’clock tests, imaginative and perceptual ones, suggesting a role of the visuoperceptual deficits in VMI alterations. It is worth noting LBD and HC did not differ in response time.

Conclusion

LBD patients with VH show alterations of VMI compared to HC. Alterations of VMI process might influence VH occurrence. Thus, it is possible that VH and VMI share neural mechanisms and are placed on a continuum along the perceptual processes. Future studies are needed to disentangle the possible role of perceptual difficulties in VMI alterations in LBD and to clarify how VMI alterations are related to VH occurrence. Furthermore, investigating VMI and its relationship with visuoperceptual skills in LBD patients could help to better characterize their neuropsychological profile.
Multi‐omics characterization of brain‐based pseudotime estimates for Alzheimer’s disease progression
Authors: Wörheide Maria A. , Batra Richa , Krumsiek Jan , Kaddurah‐Daouk Rima F. , Kastenmuller Gabi , Arnold Matthias
Published: June 2023

Background

The cascade of molecular changes that leads to Alzheimer’s disease (AD) onset and progression remains incompletely understood. Recently, researchers have utilized manifold learning techniques to construct pseudo‐temporal models of the disease using brain transcriptomics data and quantify the progression of individuals along this trajectory using pseudotime (Mukherjee et al. Nat Commun 2020;11:5781). Downstream analyses provided insights into potentially disease‐driving pathways, including links to mitochondrial dysfunction. Here, we embedded these models into a multi‐omics context to enable a more comprehensive molecular characterization of disease progression.

Method

The AD Atlas (https://adatlas.org/) integrates multi‐scale molecular data from different studies and cohorts, including omics QTLs, correlation networks, differential expression data, as well as omics associations with AD and endophenotypes. Here, we used the AD Atlas to annotate metabolites that were significantly associated with brain‐based pseudotime estimates. Metabolite (n = 667) levels were measured in brain tissue samples (dorsolateral prefrontal cortex) from 154 female ROS/MAP participants using untargeted metabolomics and tested for association using linear regression. We used the resulting set of significant metabolites as input for the AD Atlas to extract a multi‐omics context network augmented with associations to AD. Subsequently, we applied pathway enrichment analysis to derive overrepresented biological processes potentially involved in disease progression.

Result

In total, 89 of the 667 metabolites showed a significant association with pseudotime after Bonferroni adjustment, 34 of which could be mapped to the AD Atlas database. The resulting multi‐omics network contained a total of 619 genes, 197 metabolites and links to 12 AD‐related phenotypes, including CSF amyloid pathology, brain glucose uptake measured by FDG‐PET and cognitive measures. Five of the 34 metabolites and nearly one‐third of the genes contained in the network showed significant associations with AD, with transcriptional changes most pronounced in the temporal cortex (n = 193). Enrichment analysis revealed functional links to neurotransmission and bioenergetics, pathways previously implicated in the pathogenesis of AD.

Conclusion

By using metabolites as proxies for transcriptome‐derived pseudotime, we were able to investigate the molecular underpinnings of AD progression in a multi‐omics context. Our analysis provides further molecular evidence for pathways implicated in AD and emphasizes the potential of such an approach for future studies.
Implications of decreasing incidence of dementia in some countries during 1990‐2019: A global burden of disease study
Authors: Avan Abolfazl , Hachinski Vladimir
Published: June 2023

Background

Stroke and dementia share the same risk and protective factors and pose risks for each other, consequently they are considered together. Their prevalence is rising, making them the most burdensome neurological diseases worldwide. However, their incidence is falling in some countries. It becomes imperative to find out what is happening or being done right in these countries and help apply the lessons widely.

Method

We analyzed systematically trends of changes in age‐standardized dementia and stroke incidence rate per 100,000 population in 204 countries from 1990 to 2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. We also calculated the changes in the age‐standardized population attributable fraction (PAF) of dementia and stroke burden, measured by disability‐adjusted life years (DALYs), and deaths attributed to 12 risk factors with 95% uncertainty intervals (UIs).

Result

From 1990 to 2019, dementia incidence declined in 71 countries, of which 18 showed statistically significant declines, ranging from ‐12.1% (95% UI ‐16.9 to ‐6.8) to ‐2.4% (‐4.6 to ‐0.5). However, from 2010 to 2019, only 16 countries showed declines, although non‐statistically significant. The PAF of global dementia DALYs attributable to metabolic risk factors increased by 25.3% (16.9 to 38.9) from 1990 to 2019, while it decreased for behavioral risk factors by ‐17.3% (‐22.8 to ‐13.0). In particular, 163 countries showed declines in the PAF of dementia DALYs attributable to tobacco use, and 160 countries in dementia mortality attributable to high fasting plasma glucose.

Conclusion

The declining incidence of dementia in some countries, despite the growing and aging population is encouraging and urges further investigation. This approach would complement and enhance the search for a drug against Alzheimer’s disease pathology. Finding out what accounts for the decline of dementia in some countries and scaling up the lessons could begin having an impact in the near future.
Theme trends and knowledge‐relationship in frail older adults and quality of life research: A bibliometric analysis
Authors: Lee Jiyeon , Park Ji‐Hyuk
Published: June 2023

Background

Frailty is a multidimensional construct that represents an age‐related reduction in physiologic reserve and resistance to stressors. Health‐related quality of life was found to be significantly low for the frail older adults.

Method

VOS viewer is a program that graphically represents them through bibliometric analysis. Using the Web of Science data and VOS viewer program, we analyzed frail older adults and quality of life. We identified and incorporated 194 publications. We searched all years the data from 2012 to 2021 using the keywords: TITLE ((frail OR frailty OR feeble) AND (qol OR “quality of life” OR “life satisfaction” OR satisfaction OR “well‐being” OR “subjective life”)) AND DOCTYPE (ar) AND PUBYEAR 2012‐2021 LANGUAGE (English).

Result

Looking at the trend of changes in the number of published documents from 2012 to 2021, it showed an increase of 337.5% (Figure 1). The most research was included 74 and 27 cases in Geriatrics Gerontology (Figure 2). A total of 188 papers on the QoL for the frail older adults were published in 110 journals (Table 1). Australia and the United States published the largest number of papers with 29 (15.10%) (Figure 3). Studies on the quality of life of the frail older adults were conducted by researchers belonging to 434 institutions. Maastricht University, University Groningen, and Erasmus University published the largest number of papers with 6 each (Figure 4). A total of 909 keywords were searched in 188 papers, and the top 100 keywords were selected based on the frequency. There were 6 clusters and Based on the TLS and the top 5 keywords were health (49 times), mobility (41 times), disability (37 times), prevalence (37 times), and adults (33 times) (Figure 5).

Conclusion

Research on the QoL and the frail older adults is increasing. For preventive treatment for the frail older adults, which determines the quality of life, it is necessary to focus on research topics on this.