bluuebunny/crossref_metadata_2025 huggingface dataset:
Poor oral health predicts cognitive impairment in elders
Authors: Chen Jung‐Tsu , Tsai Stephanie Di‐Shan , Tseng Ching‐An , Chiou Jeng‐Min , Chen Ta‐Fu , Chen Yen‐Ching , Chen Jen‐Hau
Published: June 2023

Background

Tooth loss, periodontal disease, dementia, and Alzheimer’s disease share several risk factors in older adults. Several previous studies have reported positive associations between these dental problems and global cognitive defects. However, limited is known about the relationships among multiple dental/periodontal statuses and different cognitive domains.

Method

This six‐year (2011‐2017) cohort study includes 515 older adults (65+). Global cognition was assessed by Montreal cognitive assessment‐Taiwan version (MoCA‐T). For cognitive domains, we used logical memory tests (immediate and delayed theme and free recall) in Wechsler Memory Scale‐Third Edition (WMS‐III) to assess memory. Trail Making Test A and B was used to assess attention and executive function, respectively. Digit span‐forward and backward was used to evaluate attention and working memory/short‐term memory, respectively. Verbal fluency tests were used to assess category/semantic fluency. A Z‐score was calculated for each cognitive domain‐specific test according to baseline mean and standard deviation. Oral health status includes tooth defect (dental caries, tooth wear, cervical abrasion, retained root or crown fracture), periodontal health (disease severity from healthy periodontal status, gingivitis to periodontitis), and arch integrity (no tooth loss nor retained root or crown fracture). Generalized linear mixed models were used to assess the associations above adjust important covariates.

Result

At baseline, periodontitis was associated with poor performance in executive function [Trail Making Test A: b = ‐0.14, 95% confidence interval (CI) = ‐0.27 to ‐0.01]. The association between baseline severity of tooth defect and poor memory decreased (logical memory‐immediate theme recall: b = ‐0.05, 95% CI = ‐0.10 to ‐0.01); similarly finding was found for attention domain (digit span‐forward: b = ‐0.04, 95% CI = ‐0.07 to ‐0.001). At baseline, loss of arch integrity was associated with a better working memory/short‐term memory (digit span‐backward: β = 0.18, 95% CI = 0.01 to 0.36); as follow‐up time increased, this association decreased over six years (β = ‐0.04, 95% CI = ‐0.07 to ‐0.003).

Conclusion

Periodontitis, tooth defects, or arch integrity was associated with poor performance of cognitive domains (memory, attention, and executive function) over time. A oral health evaluation may serve as predictors of the preclinical phase of dementia in its upcoming years.
Functional hyperconnectivity is associated with higher levels of sPDGFRβ, a marker of blood brain barrier breakdown, in older adults
Authors: Contreras Joey A , Fujisaki Kimiko , Ortega Nancy E , Barisano Giuseppe , Sagare Abhay P , Zlokovic Berislav V , Toga Arthur W. , Pa Judy
Published: June 2023

Background

Apolipoprotein E4 (APOE4) has toxic effects on the cerebrovascular system, neuronal function, and functional connectivity of brain networks (e.g., default‐mode, frontal‐attention, and salience networks). The thalamus, a vital structure that acts as a relay station between many networks, has become of interest in AD research with studies showing atrophy among those with early AD and diminished cortical‐thalamic connections among those with vascular impairment. Additionally, CSF soluble platelet‐derived growth factor receptor‐β (sPDGFRβ), a marker of blood‐brain barrier breakdown, has been associated with AD risk, especially in APOE4 carriers. The present study investigated the relationship between CSF sPDGFRβ and functional connectivity in APOE4 carriers and non‐carriers.

Method

One hundred sixty‐six older adults from the Los Angeles area were selected from a larger cohort (96 females, mean age±SD = 67.4±10.7, 68 APOE4 carriers) based on availability of rsfMRI data. Image data was processed using CONN‐toolbox v19c. Grey matter was parcellated using Harvard/Oxford brain atlas, excluding cerebellum. ROI‐to‐ROI analyses were conducted selecting the thalamus as seed region averaging mean connectivity between the left and right structure of other parcellated brain regions. Linear regression models evaluated significant associations between blood oxygen level‐dependent (BOLD) and network connectivity among seed‐target regions and CSF sPDGFRβvalues, while covarying for age and sex. Comparison of averaged functional connectivity values between seed and all target regions among APOE4 carriers and non‐carriers was also examined.

Result

Higher functional connectivity between the thalamus and resting state network hub regions were associated with higher CSF sPDGFRβ (Fig 1A, 1C). Cortical regions within the networks included posterior cingulate gyrus, anterior cingulate gyrus, and frontal eye field. Averaged functional connectivity between these areas was significantly higher in APOE4 carriers compared to non‐carriers (Fig 1B).

Conclusion

The thalamus is a key subcortical structure for relaying signals across the brain for memory, attention and sleep/wakefulness cycles, and more recently with relevance to AD. These findings suggest a link between early BBB breakdown and elevated functional connectivity in brain regions known to have high synaptic activity and early pathology among non‐demented older adults at risk for AD.
A single baseline amyloid PET could be sufficient for predicting Alzheimer’s disease conversion in mild cognitive impairment
Authors: Choo Il Han , Chung Ji Yeon , Chong Ari , Ha Jung‐Min , Choi Yu Yong , Kim Hoo Won
Published: June 2023

Background

Baseline amyloid burden in mild cognitive impairment (MCI) has been linked to conversion to Alzheimer’s disease (AD), but the comparison of baseline and longitudinal changes in amyloid burden for predicting AD remains unresolved. The objectives of this study aimed to compare the prognostic ability of baseline and longitudinal changes in amyloid burden in MCI patients.

Method

Seventy‐five individuals with MCI were recruited and examined annually by clinical interviews for a mean follow‐up of 24 months (Range 11.6 – 42.0). [18F]Florbetaben positron emission tomography (PET) scans were performed. T1‐weighted 3D volumes were acquired for co‐registration, and to define regions of interest (ROIs). We examined whether baseline and longitudinal amyloid burden changes can improve AD conversion by Cox proportional hazard model analysis and receiver operating characteristic (ROC) curve analysis.

Result

Cox proportional hazards model analysis showed that baseline amyloid burden was significantly associated with increased risk of conversion to AD (hazard ratio [HR] = 10.0; 95% confidence interval [CI], 1.15 – 85.39; p = 0.04), but longitudinal amyloid burden changes was not (HR = 0.2; 95% CI, 0.04 – 1.51; p = 0.13). When predicting AD, longitudinal amyloid burden changes had better ROC accuracy of 65.2% (95% CI, 48.4 – 82.0%) than baseline amyloid burden of 59.6% (95% CI, 40.3 – 79.0%), without statistical significance in pairwise comparison.

Conclusion

A single baseline amyloid PET could be sufficient in the prediction of AD conversion in MCI.
Association of anosmia with mild cognitive impairment and biomarkers of brain aging
Authors: Dong Yi , Li Yuanjing , Liu Keke , Cong Lin , Zhang Qinghua , Hou Tingting , Song Lin , Tang Shi , Wang Yongxiang , Du Yifeng , Qiu Chengxuan
Published: June 2023

Background

Olfactory impairment has been associated with neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease (AD). We seek to investigate the relationships of impaired olfaction with mild cognitive impairment (MCI), plasma biomarkers of AD and neurodegeneration, and neuroimaging markers of microvascular lesions and neurodegeneration among Chinese older adults.

Method

This population‐based cross‐sectional study included 4214 participants (age ≥65 years; 56.0% women) from MIND‐China who were free of dementia and examined in March‐September 2018. Olfactory function was assessed using the 16‐item Sniffin’ Sticks identification test (SSIT). In the subsamples, we measured plasma concentrations of amyloid‐β40 (Aβ40), Aβ42, total‐tau, and neurofilament light chain (NfL) using the Simoa technology (n = 1054); and quantified hippocampal volume, entorhinal cortex volume, Alzheimer’s disease‐signature cortical thickness, and white matter hyperintensities (WMHs) volume on MRI scans (n = 917). The neuropsychological test battery was used to assess memory, verbal fluence, attention, and executive function. MCI and subtypes of MCI were defined according to the Petersen’s criteria that integrated clinical judgement by neurologists and neuropsychological tests. Data were analyzed with logistic and general linear regression models.

Result

Of the 4214 participants, MCI was diagnosed in 1102 persons (26.2%), including 931 with amnestic MCI (aMCI) and 171 with non‐amnestic MCI (naMCI). Olfactory impairment (SSIT score 0‐10) was associated with an increased likelihood of MCI, aMCI, and naMCI in a dose‐response manner (p for trend<.001). In the plasma biomarker or MRI subsample, anosmia (SSIT score 0‐7) was significantly associated with plasma total‐tau (demographic‐adjusted β = 0.26; 95% CI = 0.12‐0.41), NfL (0.12; 0.04‐0.19) and MRI biomarkers of hippocampal volume (‐0.13; ‐0.22‐ ‐0.04), entorhinal cortex volume (‐0.08; ‐0.13‐ ‐0.02), and WMHs volume (0.19; 0.08‐0.30), and marginally associated with Alzheimer‐signature cortical thickness (‐0.02; ‐0.05‐0.00, p = 0.08), but not with plasma Aβ concentrations (P>0.05).

Conclusion

Anosmia may be a clinical marker for preclinical dementia and neurodegeneration among older adults. Microvascular and neurodegenerative lesions in the brain may be the common neuropathological pathways linking anosmia with cognitive impairment.
Teleconsultation by a nurse as preliminary approach to home visits in older patients affected with dementia
Authors: Gareri Pietro , Pagano Lucia , Nisticò Michelangelo , Armeli Carmela
Published: June 2023

Introduction

Telehealth uses video calling and other technologies to support patients and their caregivers at home. Teleconsultation by a nurse provides advantages for collecting information about older people’s health. The present study was aimed to assess the benefits of teleconsultation by a nurse in older home patients affected with dementia.

Patients and Methods

In the time range between January 1st and December 31th 2021, 851 requests for geriatric home multidimensional assessments were addressed to the Center for Cognitive Disorders and Dementia, Catanzaro Lido, ASP Catanzaro, Italy. Teleconsultation by a nurse was used as preliminary approach to patients affected with dementia when the request for having a home consultation by a geriatrician was not performed yet, due to the great overload even in time of pandemics, or for the difficulties of reaching people living in rural and mountain areas. The call was made to patient’s caregiver who gave an informal and verbal consent to the interview. Tests administered included functional abilities in the activities of daily living (ADL and IADL); main disease and comorbidities, drugs taken by every patient were collected too. A simple questionnaire investigated the extent patient’s caregiver appreciated this way of preliminary contact, according to the following scale: 0 = no appreciation; 1 = poor; 2 = sufficient; 3 = moderate; 4 = good; 5 = very good appreciation.

Results

130 older patients, 69 women and 61 men, mean age 79.2 ± 4.5 years old were tele‐consulted; mean ADL was 3.45 ± 0.91; IADL 0.96 ± 0.4. People were affected with Alzheimer’s dementia in 39% out of the cases, vascular dementia 34%, mixed dementia 21%, other types of dementia 6%. Teleconsultation was overall appreciated, mean score 4.07 ± 0.23.

Discussion and conclusions

Teleconsultation performed by a nurse is a fast and valuable opportunity for helping doctors in a preliminary assessment of older patients suffering from dementia. The opportunity of being monitored remotely may be particularly helpful for older adults with limited mobility and those living in rural areas. This modality of approach represents a new frontier in care and assistance to old frail people with dementia.
Cross‐sectional associations between use of time and cognition in healthy older adults
Authors: Mellow Maddison L , Smith Ashleigh E , Dumuid Dorothea , Stanford Ty , Keage Hannah , Wade Alexandra , Olds Timothy , Hunter Montana , Karayanidis Frini , Dorrian Jillian , Goldsworthy Mitchell R
Published: June 2023

Background

Physical activity, sedentary behaviour and sleep are independently associated with cognition in older adults. These time‐use behaviours are not independent, rather, co‐dependent parts of the 24‐hour day. As such, spending more time in one leaves less time for the others. The balance of the three time‐use behaviours in the 24‐hour day (or time‐use composition) should be considered to inform 24‐hour movement guidelines for cognition and dementia risk reduction in older populations. Using a compositional data analysis approach, we investigated the associations between time use and cognition in a sample of healthy older adults.

Method

347 participants (age 60‐70 years; 68% female) took part in this study. 7 days of 24‐hour time use (time spent in sleep, sedentary behaviour, light and moderate‐vigorous physical activity) were captured using accelerometry. Cognition was measured using Addenbrooke’s Cognitive Examination III (global cognition) and computerized CANTAB tests measuring memory, executive function, fluid reasoning and processing speed.

Cognitive outcomes were regressed on isometric log ratios (ilrs) of the time‐use compositions, while adjusting for age and sex demographics, to explore potential associations between cognition and time‐use behaviours. For each outcome, four sets of ilr‐coordinate systems were constructed, each with a different time‐use behaviour as the numerator of a log ratio to the mean of remaining time‐use behaviours. The regression coefficient of the first ilr‐coordinate in each of the four ilr systems therefore represented the association between increasing time in the first behaviour relative to all remaining behaviours.

Result

Age was negatively associated with performance on memory, executive function, fluid reasoning and processing speed tests. More time in SB at the equal expense of all other behaviours was associated with better memory (β = 0.65, p<.01), whilst spending more time in sleep was associated with poorer memory (β = ‐0.63, p = .02). Spending more time in moderate‐vigorous physical activity was associated with better processing speed (β = 0.25, p = .01).

Conclusion

How older adults use their time is associated with cognition. Findings suggest that moving towards a holistic understanding of time use is important to inform future dementia prevention strategies.
Pro‐inflammatory IL‐1α signaling alters cellular homeostasis of NF‐kB: the AI evaluation study
Authors: Mitrasinovic Olivera M.
Published: June 2023

Background

Increased CSF levels of interleukin‐1α (IL‐1α) in Alzheimer’s Disease (AD) have been attributed to sustained inflammation, hallmark accompanying two main disease pathologies, Αβ and p‐τ, and leading to behavioral disturbances and progressive memory loss. Disease‐repair mechanisms elicited by neurons, astrocytes or microglia have been long‐term interest of pharmaceutical companies, however, NSAIDs anti‐inflammatory therapies showed limited benefit. Aside from inducing pro‐inflammation, extracellularly membrane bound IL‐1α:IL1R activates intracellular anti‐apoptotic neuroprotective transduction pathways, affecting cell growth, differentiation, and clearance of Αβ. Distinguishing beneficial vs. cytotoxic inflammation has importance in the design and improvement of AD medications.

Method

Based on our previous findings on [IL‐1α] → [ NF‐kB] interactions, also our laboratory data, and cumulative literature data for IL‐1α, we have applied a computational AI approach to identify downstream components of the pathway affected by inflammatory response and signal transducing interactions. High‐throughput algorithmic calculations (AAIC2020 abstract #39142) were performed in the MATLAB® platform, and output data graphed in Excel as 2D or 3D connectivity diagrams, allowing monitoring kinetics of interactions and cytokine dose‐dependence. Data were validated by comparative traditional laboratory assays.

Result

Extracellular‐membrane IL‐1α :IL1R receptor binding, shown in MATLAB (MathWorks) as disappearance of free, and accumulation of complex bound IL‐1α correlates with cytoplasmic transport of NF‐kB to cell nucleus. Pro‐inflammatory inducer LPS, did not produce the same outcome, in agreement with our previous laboratory studies that showed unique pattern of synergistic IL‐1α ←→ M‐CSF growth factor induced pro‐inflammation that activates neurotrophins. Exploration of signaling connectivities showed that IKK, ΙκΒ components in NF‐kB anti‐apoptotic pathway are affected by IL‐1α in [time] and [concentration] dependent manner, demonstrating further ability of algorithm to sequentially map order of interactions. 3D connectivity graphs show NF‐kBn and ΙκB co‐regulated expressions in responds to specific, narrow [IL‐1α] → [IKK] concentration interval, allowed identification of the inflection point among variables that distinguish neuroprotection and cytotoxicity.

Conclusion

Our optimized MATLAB® methodology appears to be a useful assisted collaborative tool in pre‐clinical evaluations, and screening interacting connections among proteins altered during disease mechanism, and identification of new AD pathogenesis‐linked, enabling higher accuracy and lowering overall laboratory costs in search for disease biomarkers.
Bioinformatics pipeline to identify candidate regulatory variants in late‐onset Alzheimer’s disease (LOAD) associated regions
Authors: Lutz Michael W , Chiba‐Falek Ornit
Published: June 2023

Background

Small insertions and deletions (indels) in the human genome are substantial contributors to genetic variation and impact human traits and diseases. The role of indels in late onset Alzheimer’s disease has been understudied. Few examples, such as the intronic poly‐T variant in the TOMM40 gene, suggest that systematic exploration of indels within LOAD risk regions will advance the understanding of the genetic architecture of LOAD. Previously we developed a bioinformatics pipeline that characterizes and prioritizes candidate regulatory SNPs in enhancers located in LOAD‐GWAS regions. Here we extend the pipeline to the analysis of indels. The proposed bioinformatics pipeline progresses from indels located in LOAD‐GWAS regions to a filtered set of regulatory variants that have a predicted strong effect on transcription factor (TFs) binding.

Method

The pipeline utilized publicly available functional genomics data sources. Primarily, candidate cis‐regulatory elements (cCREs) from ENCODE and single‐cell RNA‐seq data from LOAD patient samples (synapse: syn22079621). For TF binding analysis we employed motifs from MotifDb. In addition, we used various bioinformatics software including motifbreakR.

Result

We catalogued 1230 proximal CTCF‐bound candidate cis‐regulatory elements in LOAD‐GWAS regions, 912 showed epigenetic evidence in relevant brain tissue. We catalogued 426 indels in these cCREs. These indels disrupted 391 TFs, 362 of these had snRNA‐seq data from LOAD samples. Of note, TF motifs within the APOE‐TOMM40, SPI1 and MS4A2 regions were significantly disrupted by the candidate regulatory indels. Amongst these TFs are RUNX3, SPI1 and SMAD3. Interestingly, these significant findings with the APOE‐TOMM40, SPI1 and MS4A2 regions are consistent with our prior results for SNPs.

Conclusion

This study provides an analytical framework to catalogue noncoding indel variation in cis‐regulatory elements located in LOAD‐GWAS loci and characterize their likelihood to perturb TF binding. The approach integrates multiple data types to prioritize genes and variants for validation experiments using disease models and gene editing technologies.
Neuroprotective activity of Hibiscus vitifolius L. against Colchicine induced Alzheimer’s disease in rat model
Authors: Teli Shubham
Published: June 2023

Background

Traditionally, the plant was used for various diseases, including neuronal disorders. To evaluate the neuroprotective activity of Hibiscus vitifolius L. against Colchicine induced Alzheimer’s disease in rat model.

Method

Neuroprotective activity was carried out by Alzheimer’s disease on Sprague‐Dawley rats. Alzheimer’s disease was induced by cerebrum colchicine lesion. The behavioural assessments such as locomotor activity, spatial navigation task, open field were studied along with histopathological studies.

Result

Methanolic extract of Hibiscus vitifolius L, showed neuroprotective activity by increase in behavioural activity and spatial navigation task and significant decrease in lipid peroxidation (LPO) and increase in superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), total thiol and acetylcholinesterase (AChE) Activity levels in extract treated groups as compared to Control group in anti‐alzheimer’s activity.

Conclusion

The methanolic extract of Hibiscus vitifolius L, showed neuroprotective activity against Alzheimer’s disease in rat model.
Metformin Exerted Neuroprotective Effects on Cognition in Rats with Trastuzumap‐Induced Brain Toxicity
Authors: Pintana Hiranya , Chunchai Titikorn , Arinno Apiwan , Ongnok Benjamin , Pantiya Patcharapong , Khuanjing Thawatchai , Prathumsap Nanthip , Maneechote Chayadom , Chattipakorn Nipon , Chattipakorn Siriporn C
Published: June 2023

Background

Trastuzumap (Trz) is effectively used for breast cancer patients to improve health status and reduce mortality rate. Nevertheless, several studies reported its adverse effect on brain toxicity. To date, the mechanisms of Trz‐induced brain toxicity are not fully understood. Metformin is a generic prescribed drug for type 2 diabetes mellitus, while in the past decade it also used for attenuating the adverse effects of chemotherapy. However, the effects of metformin on brain mitochondrial function, hippocampal microglial function, hippocampal synaptic plasticity, and cognitive function in Trz‐induced brain toxicity have never been investigated.

Method

Eighteen male Wistar rats were randomly divided into two groups; control group (0.9% NSS, intraperitoneal (i.p.) injection, n = 8) and Trz‐treated group (4 mg/kg for 7 days, i.p. injection, n = 16). Then, Trz‐treated rats were divided into two subgroups (n = 6/ subgroup) to receive either vehicle (0.9% NSS, daily via oral gavage) or metformin (250 mg/kg/day for 7 days, daily via oral gavage). At the end of experiment protocol, cognitive function was measured, and brains were obtained for further molecular investigation.

Result

Trz‐treated rats demonstrated an increase of mitochondrial ROS production, increased mean fluorescence intensity of ionized calcium binding adaptor molecule 1 (Iba1), decreased hippocampal dendritic spine density, decreased preferent index in novel object location (NOL) and novel object recognition (NOR) test (p<0.05, Figure 1A‐F). Metformin‐treated in Trz‐rats reversed the adverse effect of Trz by attenuated mitochondrial ROS production, decreased mean fluorescence intensity of Iba1, increased hippocampal dendritic spine density, as well as increased preferent index in NOL and NOR test (p<0.05, Figure 1A‐F).

Conclusion

Trz‐induced brain toxicity as indicated by brain mitochondrial dysfunction, decreased hippocampal microglial function, impaired hippocampal synaptic plasticity, and cognitive dysfunction, while metformin alleviated those deleterious effects. The findings in this study emphasize the roles of metformin against Trz‐induced brain toxicity and strengthen
An exploratory study on the role of occupational therapists in home‐based rehabilitation team
Authors: Lim Young‐Myoung , Lee Jae Shin , Kim Su Kyoung , Cha Tae Hyun , Yoo Doo Han , Kim Hee
Published: June 2023

Background

Cooperation among rehabilitation team member is essential in home‐based rehabilitation setting. Q‐methodology that can quantitatively analyze the subjectivity of members of the rehabilitation team was used to explore the role of occupational therapists (OTs) in home‐based rehabilitation.

Method

A five‐step implementation procedure was constructed and applied to categorize the subjectivity of the rehabilitation team members. Representative statements about the role of OTs consisted of 7 areas (52 statements). A total of 34 rehabilitation team members categorized the statements according to their subjective viewpoints, and factor analysis was conducted based on the correlation between people.

Result

The roles of OTs perceived by members of the home‐based rehabilitation team were formed into five factor. In all factor, views on the role of OTs in helping clients participate in their roles and activities at home were included. These factors included issues and directions addressed in prior literature on the development of occupational therapy.

Conclusion

In home‐based rehabilitation, OTs must play a professional role in ensuring clients to live fully at home, and cooperate with team members for an effective rehabilitation approach.
CSF markers of inflammation help identify tau pathology but not amyloid in a heterogenous clinical population
Authors: Michopoulou Sofia , Prosser Angus , Kipps Christopher , Dickson John , Guy Matt J , Teeling Jessica
Published: June 2023

Background

Neuroinflammation and activation of the immune system is an integral part of Alzheimer’s Dementia (AD) pathology. Inflammatory mediators exacerbate the production of amyloid‐β, the propagation of tau pathology and neuronal loss. This study evaluates whether CSF markers of inflammation can help evaluate changes in amyloid and tau pathology in a heterogenous clinical population.

Methods

CSF samples from 105 patients referred to the Wessex Neurology Clinic due to cognitive complaints were analysed. Measurements of AD biomarkers were used to classify the samples based on previously published thresholds (Ab42<680pg/ml for an amyloid positive test, pTau>56pg/ml for a Tau positive test and Total Tau>355pg/ml for a test positive for neurodegeneration). Based on these biomarker results, the likelihood of AD was evaluated using the Paris Lille Montpellier (PLM) scale. 102 markers of inflammation were measured on CSF using the Mesoscale and OLINK platforms. Receiver Operator Characteristic (ROC) curves were used to evaluate if inflammation markers can accurately identify patients with amyloid and tau pathology.

Results

56 patients were amyloid positive, 43 were tau positive and 44 were positive for neurodegeneration. 52 different inflammation markers were detected in over 90% of samples. From these, 26 markers correlate significantly with pTau and Total Tau measurements, while no markers correlate with Ab42 measurements. Adenosine Deaminase (ADA), an enzyme of purine metabolism and marker of cellular immunity, most strongly correlates with pTau and Total Tau (Spearman’s Rho 0.62 and 0.60 respectively, p<0.001). Analysis of Variance indicates significantly higher levels of ADA in patients with higher PLM scores and thus higher likelihood of AD (p<0.001). Finally, ROC analysis indicates that ADA can identify Tau positive patients (pTau>56pg/ml) with an Area Under the Curve (AUC) of 0.76 and Neurodegeneration positive patients (Total Tau>355pg/ml) with an AUC of 0.82.

Conclusion

In this clinical patient cohort, inflammation levels increase with tau pathology but do not change with amyloid. ADA, a marker of cellular immunity, provides a sensitive and specific marker of Tau and Neurodegeneration in AD. Further work is required to assess the prognostic capabilities of ADA in larger patient cohorts and when used in conjunction with established AD biomarkers.
Cognitive impairment in clinical hypothyroidism
Authors: Deschle Florencia , Berrios Waleska , Povedano Guillermo , Moldes Maria Sofia
Published: June 2023

Background

Hypothyroidism is a highly prevalent disease and has been associated with deficits in cognitive performance. It is generally accepted that these could be related to psychiatric symptoms. Hormone replacement therapy is the gold standard treatment for primary hypothyroidism, and it appears to be effective in correcting serum thyrotropin (TSH) values and the thyroid hormone profile. Despite the correction of the hormonal profile, some patients continue to manifest cognitive and psychiatric symptoms. The possibility of restitution of cognitive performance after achieving euthyroidism is still a matter of controversy, without having reports making any comparisons of the patient himself before and after hormonal treatment.

Method

Prospective, experimental study, own individual as control.

All subjects over 18 years of age who consult the Endocrinology Service of the Churruca Visca Hospital and in whom a diagnosis of clinical hypothyroidism is made, defined by a TSH greater than 10 mIU/L, will be included until a sample size is completed. (N) of 78 patients, calculated for an estimated prevalence of cognitive failure of 40%, including patients who meet criteria for cognitive impairment and those who, even without meeting criteria, show a detriment to their best performance, with an alpha error of 0.05 and a beta error of 0.2, assuming a 50% improvement after treatment.

These patients will be referred to the Cognitive Neurology Section of the same Hospital for a complete cognitive evaluation and depression and axiety scales.

12 months after the first evaluation, euthyroidism achieved, the same cognitive evaluation will be repeated. The comparison will be made with the subject’s own performance, evaluating the remission of cognitive impairment after the hormonal treatment is installed, and the differences in their performance even without a diagnosis of cognitive impairment, comparing the performance of the subject himself before and after treatment.

Result

We expect to find cognitive impairment, with improvements between the same patient evaluation, before and after hypothyroidsm treatment.

Conclusion

Clinical hypothyroidism is a treatable cause of cognitive failure. Although patients usually present improvements after the start of treatment, some subjects continue to present different cognitive failures once euthyroidism has been achieved.
Cognitive impairment after ICU: Comparative study of severe post‐COVID19 patients with other causes of ICU admission
Authors: Deschle Florencia , Tabernero Maria Eugenia , Cancino Jorge Jose
Published: June 2023

Background

It has been reported that some post‐COVID patients develop cognitive impairment once they overcome the acute condition.

Method

Severe post‐COVID 19 patients admitted to hospitalization for rehabilitation between October 2020 and July 2021 were included, and the performance of a control group that had no history of COVID 19 was compared. Patients with central neurological history, disorders of consciousness, or psychiatric history were excluded. An abbreviated cognitive assessment was performed. The T test was used for continuous variables with normal distribution, and the Mann Whitney test otherwise. For dichotomous variables, the Chi test was used. Significant: p<0.05.

Result

A total of 196 severe post‐COVID 19 (SCA) patients were included, 41 did not present exclusion criteria and were able to carry out the complete evaluation. The control group (C) was made up of 25 patients with similar characteristics. The median age of the PCG group was 60 years (IQ 47‐69), 56.10% male. Group C had a median age of 63 (IQ 56‐69), 80% male. The mean years of schooling was 13 years for both groups. Cognitive performance: 63.4% of the patients in the PCG group and 56% in the C group failed the initial screening test (OR 1.36; 95% CI 0.5‐3.7; p ns); 51% of the PCG group and 52% of the C group had alterations in at least 2 executive function tests (OR 0.96; 95% CI 0.35‐2.62; p ns); 46.34% of the PCG group and 56% of the C group in at least 2 memory tests (OR 0.68 CI; 95% 0.25‐1.84; p ns); 34.14% of the PCG group and 40% of the C group failed in more than one domain (OR 0.78; 95% CI 0.28‐2.17; p ns); 26.8% of the PCG group and 16% of the C group obtained results within normal limits (OR 1.92; 95% CI 0.5‐6.8; p ns). 7% of the PCG group had symptoms consistent with depression.

Conclusion

In the groups of patients evaluated, a history of severe COVID 19 was not associated with an increase in cognitive impairment compared to the control group with other reasons for ICU admission.
Cognitive profiles in severe post‐COVID 19 patients in a rehabilitation center
Authors: Deschle Florencia , Tabernero Maria Eugenia , Cancino Jorge Jose
Published: June 2023

Background

After the start of the COVID‐19 pandemic, it has been described that many patients evolve with neurological alterations, including cognitive deficits.

Method

All severe post‐COVID patients admitted to hospitalization for rehabilitation between October 1, 2020 and July 30, 2021 were included. Those with central neurological pathology, altered state of consciousness, or psychiatric history were excluded. An abbreviated cognitive assessment was performed, including MoCa, CVLT, logical memory, forward and reverse digit span, IFS, TMT, Beck Depression Inventory.

Result

196 severe post‐COVID patients were included, of which 76 did not present exclusion criteria and were able to perform the complete cognitive evaluation. The mean age was 60.8 years, 65% male. The average schooling in years was 12. 67% showed poor performance in the initial screening test; 6.58% presented an amnesic profile; 7.89% a dysexecutive profile; 34.21% showed multidomain failures; 21% presented a performance within normality. The remaining patients presented isolated cognitive failures, without being able to characterize a type of profile. 5.26% had a Beck score compatible with depression.

Conclusion

In our sample, 79% of the patients showed some type of cognitive alteration. We found a low percentage of patients with depression, contrary to what is described in the literature. We consider that the investigation of cognitive alterations and the possibility of defining a type of profile is extremely useful in order to be able to optimize all the rehabilitation work with the possibility of improving the results, social reinclusion and quality of life of patients.
Depression symptoms and risk for delirium during hospitalization and after surgery
Authors: Gaba Arlen , Li Peng , Gao Chenglu , Zheng Xi , Ulsa Ma Cherrysse , Wong Patricia M , Johnson‐Akeju Oluwaseun , Gao Lei , Hu Kun
Published: June 2023

Background

Delirium is an acute neuropsychiatric disorder associated with increased risks of Alzheimer’s disease (AD) and death; it is characterized by acute confusion commonly after stressors during hospitalization and after surgery. The long‐term relationship between depressive symptoms and risk for delirium during hospitalization and after surgery remains unclear.

Method

372,893 UK biobank participants between 2006‐2010 (mean 57.9y [SD = 8.0], 54.0% female) reported frequency (never‐0, occasional‐1, often‐2, always‐3) of four depressive symptoms (mood, disinterest, tenseness, or lethargy) in the preceding 2 weeks, followed by at least one hospitalization or surgical event during follow‐up until 2020. A depression score (0‐12) was generated as the sum of the four symptoms. This was further categorized into none (0), mild (1‐2), modest (3‐5), and severe (≥6) symptoms. Delirium was determined using ICD‐10 coding from hospitalization records. Cox proportional hazards models were used to assess the predictive value of the depression score/categories for delirium risk.

Result

5,919 (16 per 1000) newly developed delirium (median 12 years follow‐up). Increased risk for delirium during hospitalization was seen for mild (HR = 1.14, 95% CI: 0.98–1.41, p<0.001), modest (HR = 1.25, 95%CI: 1.14–1.37, p<0.001) and severe (HR = 1.29, 95%CI 1.15–1.45, p<0.001) depressive symptoms, compared to those with none, after controlling for demographics, lifestyle factors, cardiovascular risk, morbidity burden, and cognition. These findings were consistent for postoperative delirium. In sensitivity analysis, the risk of delirium in the modest/severe groups was significantly stronger in those ≥65y (HR 1.70, 95% CI: 1.56 – 1.86) than in those <65y (1.36, 95% CI: 1.24 –1.48) compared to none/mild groups (p for interaction <0.0001). A follow‐up cohort (n = 225) were reassessed for depressive symptoms 4 years later. A worsening depression score (>1 point increase), compared to no change/improved score, was associated with a 39% increased risk (HR 1.39, 95%CI: 1.03–1.99, p = 0.03) independent of baseline depression scores.

Conclusion

Greater depression symptoms predicted delirium risk during hospitalization. A more recent cohort showed that worsening trajectory of depression conferred additional risk compared to those with no change/improved score. Increased awareness for subclinical depression/anxiety symptoms may be warranted for better design of therapies/strategies to identify those at increased risk for delirium.
Low hourly wages in middle‐age are associated with faster memory decline in older age: Evidence from the health and retirement study
Authors: Kezios Katrina L , Zhang Adina , Kim Soohyun , Lu Peiyi , Glymour M. Maria , Elfassy Tali , Hazzouri Adina Zeki Al
Published: June 2023

Background

Little research has investigated the long‐term relationship between low wages and memory decline, despite the growing share of low‐wage workers in the US labor market. We examined whether cumulative exposure to low wages over 12 years in midlife is associated with memory decline in later life.

Method

We used 1992‐2016 data from the Health and Retirement Study, a biennial longitudinal survey of nationally representative samples of Americans aged 50+. We analyzed data from 3,803 individuals born 1936‐1941 using confounder‐adjusted linear mixed‐effects models. Low‐wage was defined as hourly wage lower than two‐thirds of the federal median wage for the corresponding year. Low‐wage exposure history was categorized into ‘never’, ‘intermittent’, and ‘sustained’ based on wages earned from 1992 to 2004. Memory function was measured at each visit from 2004 to 2016 by a memory composite score; on average, participants completed 4.8 memory assessments from 2004‐2016. Estimates were obtained in the total sample and within strata of sex (Nmales = 1,913, Nfemales = 1,890).

Result

At the beginning of cognitive follow‐up (2004) our sample was on average 65 years old with a mean memory score of 1.15 standard units. The confounder‐adjusted annual rate of memory decline among workers who never earned low wages was ‐0.12 standard units, 95% CI: [‐0.14, ‐0.10]. Compared with this, memory decline among workers with sustained earning of low midlife wages was significantly faster (βtime*sustained:‐0.012, 95% CI: [‐0.02, ‐0.01]), corresponding to an annual rate of ‐0.13 standard units for this group. Put into terms of “excess cognitive aging”, the cognitive aging experienced by workers with sustained exposure to low midlife wages over a 10‐year period is what workers never earning low‐wages would experience in 11 years. Similar associations were found among males and females. No significant association between intermittent earning of low wages and memory decline was observed.

Conclusion

Sustained earning of low wages in midlife was significantly associated with a downward trajectory of memory performance in older age. Enhancing social policies to protect low‐wage workers (e.g., increasing minimum wage) may be especially beneficial for the cognitive health of individuals with sustained low‐wage employment in midlife.
Blood‐brain barrier permeable antibodies for Alzheimer’s potential therapeutic and diagnostic applications
Authors: Bhatt Ram , Ramos Oscar
Published: June 2023

Background

Alzheimer’s disease (AD), the most common cause of dementia, is a slowly progressing neurodegenerative disorder that has become an escalating global epidemic with an unbearable emotional and physical strain on patients, loved ones, and their caretakers. So far, there is no cure or treatment to alter its progression or improve cognition. The reasons for such a failure to develop disease modifying therapy for AD can probably be best described, in our opinion, as to the lack of understanding of what the real disease trigger is and the inability of most of the potentially disease modifying agents to cross the blood‐brain barrier ((BBB) in therapeutically effective doses. Mouse monoclonal antibodies (mAbs) against amyloid‐beta (Aβ) and Tau proteins have been employed to normalize the levels of these proteins in the brain despite their low (0.1%) reported brain uptake. Though Aβ levels have been reduced, either through direct target engagement in the brain or most likely due to the so called “Sink Hypothesis” in multiple clinical trials, cognition improvement has not been observed so far. It appears that memory deficit may be related to early events such as mitochondria and lysosomal dysfunction, axonal demyelination, and neuroinflammation, etc. that take place long before symptoms and protein aggregation are observed.

Method

To demonstrate BBB permeability proof‐of‐principle we developed heavy‐chain only antibody for amyloid‐beta (1‐42) by immunizing animals with a synthetic antigen. Blood from the immunized animals was collected and processed using standard published methods to obtain heavy‐chain only antibody, referred to as the SMART* Molecule (SM). [SMART* is an acronym that stands for Specific Molecular Architecture for Recognition and Therapy].

Result

Low dose (1.5 mg/Kg) tail‐vein injection of Aβ‐SM in transgenic AD mice exquisitely decorated amyloid‐plaque as shown by tissue histology of brain slices demonstrating potential diagnostic application of Aβ‐SM. One weekly tail‐vein injection with the same low dose for 12 weeks in AD transgenic mice cleared amyloid plaque, oligomeric and fibrillar, by about 60% compared to the untreated mice, thus demonstrating therapeutic potential of Aβ‐SM.

Conclusion

SMART Molecules, heavy‐chain only antibodies, appear to have therapeutic and diagnostic potential for neurodegenerative diseases of the central nervous system.
Effects of physical activity and the combination with a multidisciplinary rehabilitation program on physical capacities, neuromotor components and depressive symptoms in patients with Alzheimer’s disease
Authors: Antunes Mariana S , Souza Maira S , Takeda Osvaldo H , Ueno‐Pardi Linda M
Published: June 2023

Background

Alzheimer’s disease (AD) is one of the most prevalent dementias in the elderly and is associated with a high rate of morbidity and mortality. AD is also accompanied by functional changes and psychiatric disorders in older adults with AD. In addition to drug treatment, non‐pharmacological interventions can contribute to attenuating cognitive and functional decline, improving well‐being and psychiatric symptoms. The aim of the present study was to analyze the effects of interventions with isolated physical activity program and multidisciplinary rehabilitation program (including physical activity sessions, physiotherapy, occupational therapy, speech therapy, art therapy, games, cognitive and computer stimulation) on physical capacities, neuromotor components and depressive symptoms in elderly with AD.

Method

Third four elderly patients with previous diagnosis of AD were include in control group (CG = 8), intervention group with isolated physical activity (PAG = 12), and the multidisciplinary rehabilitation group (MG = 14). All participants underwent neuropsychological and neuropsychiatric evaluation, physical activity level questionnaire and functional tests (including muscular endurance, aerobic capacity, flexibility and agility/dynamic balance) at the beginning and the end of the study. The physical activity program included aerobic exercises, motor coordination, strength, flexibility, and cool down for 3 months, twice a week, with 75 min each session. The MG group participated in physical activity sessions, physiotherapy, occupational therapy, speech therapy, art therapy, games, cognitive and computer stimulation. The duration of these workshops was 60 to 90 min each (totaling 6 hours a day), 2 days a week, for 3 months.

Result

There was a significant improvement in the physical capacities, neuromotor components, and total physical activity levels of the PAG and MG in relation to the CG. In addition, MG intervention was also able to reduce depressive symptoms in patients with AD.

Conclusion

Interventions with isolated physical activity program and in a multidisciplinary team were effective for improvement of the physical capacities and neuromotor components of the elderly with AD.
Effects of multimodal physical activity program in the cognive functions and functional fitness test in elderly with and without Alzheimer Disease
Authors: Souza Maira S , Antunes Mariana S , Takeda Osvaldo H , Ueno‐Pardi Linda M
Published: June 2023

Background

Alzheimer’s Disease (AD) is the most prevalent disease among all dementias, and is characterized by progressive deficits in cognitive function and activities of daily living.The aim of this study was compare effects of multimodal physical activity program in functional capacity, memory, and attention in elderly with and without AD.

Method

Eighteen elderly with AD were ramdomized into the control (AD‐C) or multimodal physical activity program (AD‐T) groups. Also twenty without AD were divided in the control (NAD‐C) or physical activity program (NAD‐T) groups. All participants performed the international physical activity questionnaire, neuropsicological evaluation using Mini Mental State Examination, Syndrom Kurztest (SKT), clinical dementia rating. The functional fitness test was evaluated by the muscular resistance (30‐second chair stand and arm curl), aerobic capacity (2‐minute step in the place), lower and upper body flexbility (chair sit‐and‐reach, and back scratch tests) and agility/dynamic balance (8‐foot up and go). The shoulder and ankle amplitude were measured using a Fleximeter. The multimodal physical activity program included warm up, aerobic exercises, strength, flexibility, and cool down for 3 months, twice a week, with 75 min each session for NAD‐T and AD‐T groups.

Result

The physical activity program significantly increased the leisure‐time physical activity level, upper body muscular strength, aerobic capacity, upper and lower body flexibility, shoulder and ankle extension range in the NAD‐T and AD‐T (P<0.05). Also increased agility/dinamic balance compared to the AD‐C group (P<0.05). Concerning the cognition, the multimodal training improved SKT‐memory in both groups NAD‐T and AD‐T (P<0.05). SKT‐atention improved in the NAD‐T group (P<0.05).

Conclusion

The multimodal physical activity program was effective in increasing the level of leisure‐time physical activity, aerobic capacity, muscle strength, lower limb flexibility, shoulder extension, and memory, independent of the AD. Additionaly, the program attenuated the decline in agility/dinamic balance compared to the AD‐C group. Attentional function improved in the NAD‐T group. These benefits may contribute to a better performance in activities of daily living, reduction of falls and attenuation of the decline of cognitive functions in elderly people with and without AD.