bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Helianthus annuus Flower Extract on Biomarkers of Alzheimer’s Disease
Authors: Joshi Ankur , Malviya Dr Neelesh
Published: December 2023

Background

Alzheimer’s disease (AD) is a slowly progressive disease of the brain that is characterized by the impairment of memory and eventually by disturbances in reasoning, planning, language, and perception. Amyloid β‐peptide (Aβ) is main source of oxidative stress in AD because it can acquire a free‐radical state that contributes to its toxic effects. Aβ‐induced cytotoxicity is caused by intracellular accumulation ofreactive oxygen species, which leads to lipid peroxidation and cell death. Helianthus annuus flower is known for its nutritional value and having many medicinal benefits as well. Helianthus annuus flower contain many medicinally essential phytoconstituents, such as phenol, flavonoid, and carotenoid.

Method

STZ administration through route such as intracebroventricular or intraperitoneal injection produces reduced cognition and increased cerebral aggregated Aβ fragments, total tau protein, and Aβ deposits. These changes were accompanied with decreased glycogen synthase kinase (GSK‐3) alpha/beta ratio (phosphorylated/total) in the brain. Administration of STZ in a rodent’s brain has been shown to produce neuroinflammation, oxidative stress and biochemical alterations, which is considered to be a valid experimental model of the early pathophysiological changes in neurodegenerative disease.

Result

Two doses (100 and 200 mg/kg) of the flower extract from Helianthus annuus were given over the course of seven days. The standard agent utilised was piracetam (120 mg/kg). Oral administration of Helianthus annuus flower extract resulted in a considerable reduction in A1‐40 58 0.21 (100mg/kg) and 53 0.79 (200mg/kg) and A1‐42 17 0.89 (100mg/kg) and 15 1.02 (200mg/kg). Helianthus annuus flower extract increased the levels of the following brain antioxidant enzymes at 100 mg/kg and 200 mg/kg, respectively: CAT (15.5 2.8** and 14.0 1.12**), SOD (13.5 1.4** and 18.3 1.7**, GSH (203.3 15.3** and 218.0 13.5**), TBARS (200.3 7.3** and 208.0 11.0**). AChE activity was significantly decreased when Helianthus annuus flower extract was taken orally at doses of 100 mg/kg and 200 mg/kg, respectively.

Conclusion

Data of the present study revealed that Helianthus annuus flower significantly decreased the brain Amyloid β 1‐42 and AChE activity in rats. Data revealed that administration of both Helianthus annuus flower (100mg/kg) and Helianthus annuus flower (200mg/kg) increased the activity of SOD and CAT.
Identification of novel drug targets for Alzheimer’s disease by integrating genetics and proteomes from brain and blood
Authors: Ou Ya‐nan
Published: December 2023

Background

Genome‐wide association studies (GWASs) have discovered numerous risk genes for Alzheimer’s disease (AD), but how these genes confer AD risk is challenging to decipher.

Method

To efficiently transform genetic associations into drug targets for AD, we employed an integrative analytical pipeline using proteomes in brain and blood by systematically applying proteome‐wide association study (PWAS), Mendelian randomization (MR) and Bayesian colocalization.

Result

Collectively, we identified the brain protein abundance of 7 genes (ACE, ICA1L, TOM1L2, SNX32, EPHX2, CTSH, and RTFDC1) are causal in AD (P<0.05/proteins identified for PWAS and MR; PPH4>80% for Bayesian colocalization). The proteins encoded by these genes were mainly expressed on the surface of glutamatergic neurons and astrocytes. Of them, ACE with its protein abundance was also identified in significant association with AD on the blood‐based studies and showed significance at the transcriptomic level. SNX32 was also found to be associated with AD at the blood transcriptomic level.

Conclusion

Our current study results on genetic, proteomic and transcriptomic approaches has identified compelling genes, which may provide important leads to design future functional studies and potential drug targets for AD.
Caspase‐dependent Apoptosis Inhibition Improves Cognitive Function in Myocardial Infarction Rats
Authors: Jinawong Kewarin , Apaijai Nattayaporn , Piamsiri Chanon , Maneechote Chayadom , Pintana Hiranya , Chattipakorn Nipon , Chattipakorn Siriporn C
Published: December 2023

Background

Cognitive impairment was frequently found following myocardial infarction (MI). Apoptosis, particularly in the hippocampal area, has been proposed as a mechanism involving in the cognitive impairment through the initiation of brain cell death and subsequently dendritic spine loss. The hypothesis of this study is that the inhibition of apoptosis using a pan‐caspase inhibitor (Z‐VAD‐FMK) improves hippocampal dependent cognitive function in MI rats via attenuating brain apoptosis and dendritic spine loss

Method

Male Wistar rats were divided into sham operation or permanent left anterior descending coronary artery ligation‐induced MI. After one week, MI rats with LVEF less than 50% were randomly assigned to one of three interventions: (1) MI‐vehicle (DMSO), (2) Enalapril as a positive control (10 mg/kg/day, PO), and (3) A pan‐caspase inhibitor (Z‐VAD‐FMK, 1 mg/kg/day, IP). All rats received the intervention for 4 weeks, then cardiac function and hippocampal‐dependent cognitive function were assessed before they were sacrificed. Hippocampal dendritic spine density and apoptotic protein expression were determined.

Result

MI‐vehicle rats exhibited cardiac dysfunction (as shown by a decrease in %LVEF), cognitive impairment (as shown by decreased %preference of novel object recognition), and hippocampal dendritic spine loss. Furthermore, our data showed that apoptosis was significantly increased (as shown by increased cleaved‐caspase 3/Pro‐caspase 3 levels) in MI‐vehicle rats, compared with the sham rats (as shown in Figure). Treatment with Z‐VAD‐FMK and enalapril equally improved cardiac function, cognitive function, and increased hippocampal dendritic spine density, compared with the MI‐vehicle rats. Z‐VAD‐FMK demonstrated a greater benefit in reducing apoptosis than enalapril in the brain of MI rats.

Conclusion

Apoptosis inhibitor shared similar efficacy with enalapril in improving cognitive function through suppressing brain apoptosis and restoring hippocampal dendritic spine density in MI rats.
Are noradrenergic and orexinergic systems contributing to sleep‐wake patterns in early and late‐onset Alzheimer’s Disease?
Authors: Falgàs Martínez Neus , Muñoz‐Moreno Emma , Mayà Gerard , Muñoz‐Lopetegui Amaia , Marrero‐González Paula , Val‐Guardiola Andrea , Guillén Núria , Sarto Jordi , Bosch Beatriz , Balasa Mircea , Fernandez‐Villullas Guadalupe , Antonell Anna , Walsh Christine M , Ruoff Leslie , Joan Santamaria , Bargalló Núria , Lladó Albert , Morales‐Ruiz Manuel , Iranzo Álex , Grinberg Lea T. , Sanchez‐Valle Raquel
Published: December 2023

Background

Neuropsychiatric symptoms, including sleep‐wake disturbances, are more common in Early‐onset Alzheimer’s disease (EOAD) than in Late‐onset AD (LOAD)(Falgàs, EurJNeurol2022). The pattern of tau‐related degeneration of wake and sleep‐promoting neurons determine sleep‐wake profiles in neurodegenerative disorders (Oh, JAMANeurol2022). We hypothesize that distinct patterns of noradrenergic (locus coeruleus‐LC) and orexigenic (hypothalamus‐HT) degeneration contribute for the differential sleep‐wake patterns between EOAD and LOAD.

Method

A group of 21 participants (7 EOAD, 18 LOAD) with a diagnosis of AD confirmed by cerebrospinal fluid biomarkers (CSF) were recruited from Hospital Clínic de Barcelona. Participants underwent sleep questionnaires (Pittsburg Sleep Quality Inventory‐PSQI and Epworth Sleepiness Scale‐ESS), 2‐week actigraphy (MotionWatch8, CamnTech) and 3T‐neuromelanin‐sensitive MRI to measure locus coeruleus (LC) and hypothalamus (HT) volumes. Sleep, napping, and circadian parameters were obtained (MotionWare).

Result

The preliminary results showed no differences in sex (71vs.61% women) or disease stage (CDR 0.5: 85% vs.72%). The amnestic phenotype was prevalent (100 vs.78%). EOAD had longer daytime napping (93.2±74 vs. 58.2±28min, p<0.05), later fell asleep times (0:42am vs. 11:30pm, p<0.05) and higher central phase measure (4.4±0.5 vs. 3.5±1 h, p<0.05, midpoint between fell asleep and wake‐up) than LOAD. Daytime napping correlated with ESS (r = 0.53, p<0.01). Other parameters such as actual sleep time, sleep efficiency, sleep latency, or fragmentation index showed no differences. PSQI did not correlate to any measures. LC‐volumes were lower in EOAD than in LOAD (24.4±7mm3 vs. 33.3±6 p<0.01). In contrast, HT‐ trended towards higher volumes in EOAD (416.8±38 vs. 392.9±36, p = 0.09), being inversely correlated to the age at onset (r = ‐0.47, p<0.05). The central phase measure was inversely correlated to LC‐volumes (r = ‐0.47, p<0.05) but not to HT. Further analyses with increased sample size, CSF noradrenaline and orexin will be performed.

Conclusion

Greater daytime sleepiness and circadian dysfunction could be main differing traits regarding sleep‐wake patterns between EOAD and LOAD. An opposite pattern of degeneration within wake‐promoting systems consisting of higher degeneration of the LC‐noradrenergic system and relative preservation of the HT‐orexigenic in EOAD in contrast to LOAD might underlie differing sleep‐wake phenotypes. Age‐related hypothalamic volume loss can be adding to AD driven loss resulting in higher volumes in EOAD.
Factors associated with dementia attitudes in an adolescent cohort: structural equation modelling
Authors: Hassan Esra , Hicks Ben , Tabet Naji , Farina Nicolas
Published: December 2023

Background

Dementia related stigma is a key barrier to people living well with dementia. The global action plan on the public health response to dementia outlines the need to tackle the stigma towards dementia among the general population (WHO, 2017). Adolescents represent an under researched group among the general population but may already have experience of dementia and will become future carers or healthcare workers. Adolescents are ideal targets for anti‐stigma initiatives since the adolescence period has a key role in attitude formation. Understanding the factors involved in dementia attitude formation is useful when developing anti‐stigma initiatives. This study aims to identify predictors of dementia attitudes in adolescents.

Method

This is a cross‐sectional study using secondary data analysis. 470 participants aged 12‐15 years old from secondary schools in the Southeast of England, United Kingdom completed validated questionnaires relating to dementia attitudes (KIDS and Brief A‐ADS) as well as demographic information. A path analysis via a structural equation model was used to test for direct and mediatory effects between dementia attitudes, contact, career interest, empathy and sex.

Result

The overall fit of the model was very good, χ2(16) = 16.913, p = .15, CFI = .99, GFI = .99, AGFI = .97, TLI = .98, RMSEA = .03, Pclose = .82. There was a significant direct effect observed between the following paths; sex to dementia attitudes (p = .001), attitudes to willingness to work with people with dementia, (p < 0.001), empathy to dementia attitudes (p = .01), contact to empathy (p = .01), and empathy to contact (p < 0.001). Within the final structural equation model, empathy was a key mediator between contact and dementia attitudes.

Conclusion

This study highlights the pivotal role that contact with dementia can have in influencing dementia attitudes in adolescents with empathy a key mediator between contact and dementia attitudes. The translational significance of this work is that it provides organizations with the knowledge needed to create effective policy and interventions. Interventions that use contact should consider stimulating empathetic responses to shape dementia attitudes.
Proteomic comparison between CSF samples and CSF‐derived EVs from patients with Alzheimer’s disease, Parkinson’s disease and Lewy Body dementia
Authors: Hirschberg Yael , Boonen Kurt , Engelborgs Sebastiaan , Vermeiren Yannick , Mertens Inge
Published: December 2023

Background

Extracellular vesicles (EVs) have recently been considered as a potential biomarker source for a variety of diseases, including neurodegenerative disorders. EVs are important mediators of intercellular communication due to their capacity to transfer genetic material, lipids and proteins. By means of their communication role, interesting biomarkers are often enriched in EVs compared to total biofluid. In this study, this hypothesis is tested as untargeted proteomics is performed on both CSF samples and CSF‐derived EV samples from the same cohort with different dementia diseases.

Method

CSF samples were collected from 297 patients (with Alzheimer’s disease (AD), Parkinson’s disease (PD), PD with cognitive deficit (PDCD), PD with dementia (PDD), Lewy Body dementia (LBD)) and healthy controls (HC). Furthermore, EVs were obtained from 500µL of the same CSF samples, isolated by SmartSEC HT. Total protein quantification was measured using absorbance at 280nm for CSF samples, and by fluorescence (NanoOrangeTM) for CSF‐derived EV samples. For both types of sample, LC‐MS/MS based proteomics analyses were performed.

Result

Total protein quantification showed multiple significant differences between all groups, both in CSF samples and in CSF‐derived EV samples. In both types of sample, PDCD group showed the highest protein concentration after normalization. In regard to LC‐MS/MS results, a first analysis resulted in a total of 3036 identified proteins (1564 protein groups) for the CSF samples, and 6627 proteins (3360 protein groups) for the CSF‐derived EV samples. The current analyses show four statistically differentially expressed proteins between CSF‐derived EV samples from HC and AD, AD and PD, LBD and PDCD. By the time of AAIC2023, also CSF samples will be analysed and a comparison will be drawn between both types of sample.

Conclusion

As more in‐depth proteomic analyses will be performed by AAIC2023, a definite conclusion will be given at the conference. For now, already differences in total protein concentration were observed between the different disease groups and LC‐MS/MS of CSF‐derived EV samples resulted in four statistically differentially expressed proteins.
Can german discharge management by law support people with cognitive impairments across sectors
Authors: Schumacher‐Schönert Fanny , Boekholt Melanie , Nikelski Angela , Kracht Friederike , Vollmar Horst Christian , Hoffmann Wolfgang , Kreisel Stefan , Thyrian Jochen René
Published: December 2023

Around 1.8 million people in Germany live with dementia. Ascending trend. Discharging people with cognitive impairment from the hospital and transitioning them to outpatient care brings special challenges and presents the health care system with a new and increasingly important task. In Germany there are legal efforts (§39 paragraph 1a, SGB V) to close gaps, wich are supposed to develop the discharge and transfer process. A relevant Cochrane review provided further impressions of the effectiveness of individualized discharge planning.

The analysis is part of the intersec‐CM study; a multi‐centered, randomized controlled study to analyze the effectiveness of an intersectoral intervention and care management system. Discharge documents of all documents available at the time of discharge could be recorded by n = 382 subjects. This corresponds to a sample size of 95.02% of the total study population.

Aim of the presentation is to provide an overview of the documentation process for discharge and transfer management in everyday clinical practice after the discharge management law came into force in accordance with §39 paragraph 1a, SGB V. It answers the research question „What form does documentation take within the framework of statutory discharge management for people with cognitive impairments?“ It highlights further characteristics of the discharge documents for vulnerable patient groups and shows which contents in the discharge documentation play a role in order to be able to provide cross‐sectoral support for people with cognitive impairment.

There can be shown three findings; formal, content‐related and translational results. Even formal results show, that there is no standardization for discharge documents. Further content‐related results confirm, that the documentation process according to §39 paragraph 1a, SGB V has large documentation gaps. The documentation appears to be heterogeneous and communication for follow‐up treatment needs improvement. The greatest learning objective is to create awareness for standardization in the discharge documentation for people with cognitive impairment.
Machine‐learning derived white matter signatures and the risk of dementia, stroke and mortality: the Rotterdam Study
Authors: Rosbergen Mathijs T. , Wolters Frank J. , Vinke Elisabeth J. , Ikram M. Arfan , Vernooij Meike W
Published: December 2023

Background

White matter hyperintensities (WMH), loss of white matter (WM) volume and WM microstructural integrity are important risk indicators of stroke and dementia, albeit of heterogeneous nature. Use of machine learning techniques may unravel different patterns of white matter injury, with distinct underlying pathologies and disease risk.

Method

We measured WMH volume, WM volume, global fractional anisotropy (FA) and global mean diffusivity (MD) in 5205 participants (mean age 64.9 years, 56.0% women) of the population‐based Rotterdam study with brain MRI between 2005 and 2016. We performed hierarchical clustering on age‐standardized imaging parameters to identify separate clusters of white matter injury, and compare determinants across clusters. We then determined the association between clusters and risk of dementia, stroke and mortality, using Cox proportional hazard models adjusted for sex, education, APOE‐ε4 and cardiovascular risk factors.

Result

We identified four distinct white matter signatures: (i) cluster with above‐average microstructural integrity and little WM atrophy and WMH, (ii) cluster with above‐average microstructural integrity and little WMH, yet substantial WM atrophy, (iii) cluster with poor microstructural integrity and substantial WMH, yet little WM atrophy, and (iv) cluster with poor microstructural integrity, substantial WM atrophy, and average WMH load. There were no clear differences between clusters in APOE genotype and cardiometabolic risk factors, except for higher prevalence of hypertension in cluster (iv). Cluster (iii) contained more women, and participants in clusters (iii) and (iv) had more microbleeds and lacunes. During a median 10.7 years of follow‐up, 272, 210, and 844 cases of dementia, stroke, death occurred, respectively. In fully adjusted models, dementia risk was increased for clusters (ii) (HR 1.57 [95%CI:1.04‐2.37]), (iii) (HR 2.43 [95%CI:1.68‐3.52]) and (iv) (HR 1.78 [95%CI:1.22‐2.62], compared to cluster (i). Moderate associations of clusters (iii) and (iv) with incidence stroke attenuated and were no longer statistically significant after adjustment for cardiovascular risk factors, while only cluster (iii) was associated with a small increase in mortality (HR 1.30 [95%CI:1.07‐1.58]).

Conclusion

Machine‐learning derived white matter signatures are differentially associated with dementia, stroke and mortality. Further research is needed to pinpoint differences in underlying pathology, and assess potential benefit of clusters for risk stratification.
Delineating amyloid peptide signatures among heterogenous plaque population in Alzheimer’s Disease
Authors: Koutarapu Srinivas
Published: December 2023

Background

Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting nearly 12% of individuals older than 65 years. The disease poses an immense societal challenge and personal suffering, particularly as there were still no curative treatments as the pathogenic mechanisms of AD remain elusive. One of the main challenge would be to understand the chemical basis of heterogeneity involved in the formation of variety of plaque polymorphs. These plaques are known to be extracellular deposits of amyloid beta (AB) peptide. In this study we aim to investigate the chemical nature of structuraly diverse plaque polymorphs in patient samples with sporadic AD, familial AD and Cognitively unimpaired pathological ageing.

Method

We employed a novel chemical imaging strategy combining microscopy with matrix assisted laser desorption/ioninsation ‐ mass spectrometry imaging (MALDI‐MSI) to delineate AB signatures of heterogenous plaque polymorphs. These plaques are then grouped into sAD‐diffused plaques (DP), sAD‐cored plaques (CP), sAD coarse grain plaques (sAD‐CG), CU‐AP diffused plaques(DP of CU‐AP), fAD cored plaques (fAD‐CP) and fAD coarse grain plaques (fAD‐CG) along with amyloid vasculature from sAD and fAD based on the high resolution hyperspectral microscopy images combined with multivariate image analysis performed on MALDI‐MSI data. These plaques are then investigated for differences in the AB signatures.

Result

Aβ1‐40 is more abundant in more compact plaques like CG and CP in comparison to DP and DP of CU‐AP. Aβ3pE‐40 in less aggregated diffused plaques of CU‐AP than cored plaques of sAD.

Conclusion

This study provides neurochemical information of the amyloid plaque polymorphs crucial for the development of a biomarker . Our data suggests Aβ1‐40 and 3pE depositions are critical in plaque maturation . fAD plaques are more compact than in sAD, larger extend of Aβ1‐40/1‐42. We also present the chemical characterization of coarse grain plaques for the first time. Similarities of CG to CAA point towards vascular involvement in the formation of coarse grain plaques
Does rTMS improve cognitive function in age‐related neurodegenerative diseases? A systematic review and meta‐analysis
Authors: Miller Amy , Allen Richard J. , Juma Alisha A. , Chowdhury Rumana , Burke Melanie Rose
Published: December 2023

Background

High‐frequency, repetitive transcranial magnetic stimulation (rTMS) targeted over the dorsolateral prefrontal cortex (DLPFC) is widely used in research to promote neuroplasticity and cognitive enhancement. RTMS is a promising intervention to tackle cognitive decline in people living with age‐related neurodegenerative diseases. However, there is currently no systematic evidence examining the effects of DLPFC‐targeted, high‐frequency rTMS on cognitive function in this population. The aim of this systematic review was to evaluate the efficacy and moderators of this treatment intervention.

Method

A comprehensive literature search of five electronic databases was performed to identify articles published before October, 2022. Following PRISMA guidelines, the identified articles were screened, data was extracted, and the methodological quality was assessed using the Cochrane tool, Risk of Bias 2 (ROB2). Meta‐analyses were performed using R Studio (v4.1.2).

Result

Sixteen studies involving 474 participants met the inclusion criteria, of which 8 studies measured global cognitive function. The results from the random‐effects meta‐analysis showed rTMS significantly improved global cognitive function relative to control groups shown by a large, significant effect size (g = 1.39, 95% CI, 0.34‐2.43; p = .017). No significant effects were found between subgroups or for individual cognitive domains.

Conclusion

High‐frequency rTMS, targeted over the DLPFC, appears to improve global cognitive function in people living with age‐related neurodegenerative diseases. However, these results should be interpreted with caution due to the small number of studies included, and high between‐study heterogeneity.
Effects of mindfulness training and exercise on cognitive function in healthy older adults without dementia: the MEDEX clinical trial
Authors: Lenze Eric J.
Published: December 2023

Background

A 2×2 factorial multi‐site randomized clinical trial was conducted to determine whether Mindfulness Based Stress Reduction (MBSR), exercise, or their combination improve cognitive function in older adults..

Method

585 older adults (aged 65‐84; mean age 71.5, 72.5% women) with subjective cognitive concerns but no dementia were randomized to MBSR, exercise with aerobic, strength and functional components, combined MBSR and exercise, or a health education control group. Interventions lasted 18 months and consisted of group‐based classes and home practice.

Result

Neither MBSR, exercise, nor their combination significantly improved either primary outcome of memory or cognitive control (composites of neuropsychological tests), or secondary outcomes of hippocampal volume, DLPFC thickness and surface area, functional cognitive capacity or self‐reported cognitive concerns.

Conclusion

Among older adults with subjective cognitive concerns but without dementia, mindfulness training, exercise, or both did not significantly improve cognitive or brain structural outcomes.
Transitioning from dementia‐related stigma to a Community Level Dementia Screening Program in Rural Kenya (DEM‐SKY)
Authors: Musyimi Christine W. , Ndetei David , Farina Nicolas , Masila Joe , Muyela Levi A. , Mutunga Elizabeth Kasimu
Published: December 2023

Background

Primary health care providers face the challenge of making timely dementia diagnosis due to limited time available to interact with patients resulting in stigma, neglect and abuse. With training, these providers can collaborate with Community Health Workers (CHWs) to improve dementia detection and articulate the needs of communities whilst mobilizing resources that are salient in decision‐making, care coordination and service delivery processes. In this study, we outline the process that led to integration of a Community Level Dementia Screening Program in Rural Kenya (DEM‐SKY).

Method

As part of the Strengthening Responses to Dementia in Developing Countries (STRiDE) project, ten CHWs were trained to deliver a dementia anti‐stigma intervention to 59 members of the general public in rural Kenya, through four bi‐weekly psycho‐education sessions. This led to increased number of people turning up for dementia screening at a county referral hospital. However, due to lack of knowledge and busy waiting lines at the hospital, discussions on how to integrate dementia screening within the hospital began.

Result

Findings from the STRiDE project formed the basis of integrating a community‐level dementia screening programme in Makueni County Referral Hospital in Kenya, a program that has seen more than 600 adults aged 60 and above screened for dementia by CHWs in a period of one month. Through partnership and collaboration with the hospital, a recording and reporting system for people living with dementia was established to provide an indication of the number of dementia cases and individuals referred from the community. This was made possible through: (i) training formal and informal providers on importance of dementia screening, (ii) continued awareness in communities to change existing negative dementia perceptions and (iii) motivating CHWs through project visibility materials and recognizing them in community events.

Conclusion

Public awareness and stigma reduction using CHWs can be a precursor to strengthening health care systems through routine dementia screening for older people in community settings. This integration process also requires using task‐sharing approaches in order to promote timely detection and improve care coordination at all levels of care, thus forming a basis for formulation, implementation of policy and service planning.
Using a newly validated algorithm to estimate prevalence and incidence of Alzheimer’s Disease and related dementias in Medicare claims
Authors: Afonso Ana Sofia , Schroeder Krista Marie , Wang Huabo , Grace Sarah , Phipps Adam , Sims John R.
Published: December 2023

Background

Few published studies have estimated the prevalence and incidence of Alzheimer’s disease (AD) and AD related dementias (ADRD) in the US Medicare population using fit‐for‐purpose claims algorithms. This study utilized a newly validated administrative claims algorithm for identifying ADRD, the “1‐year Bynum‐Standard ADRD algorithm”, adjusted for positive predictive value (PPV) and sensitivity, to estimate the 2019 annual prevalence and annual incidence of ADRD in US Medicare patients 65+ years of age.

Methods

This study utilized Medicare Part A and B claims (Fee‐For‐Service and Medicare Advantage) limited to patients with at least one 2019 medical encounter. The study’s source population was limited to those 65+ years of age with Medicare Part D coverage and 1‐year pre‐encounter continuous enrollment. Utilizing the 1‐year Bynum‐Standard ADRD claims algorithm, patients with ADRD were compiled. As the Brynum‐Standard algorithm includes AD as well as related dementias, a second AD cohort was built adapting the algorithm’s code list to include only specific AD diagnoses. Prevalence was calculated as a percent of the source population after adjustment for PPV and sensitivity of the algorithm. Incidence calculations required a 1‐year pre‐diagnosis exclusion period.

Results

From 53.9 million Medicare patients with at least one 2019 medical encounter, 33.3 million patients qualified for the source population. Of these patients, 2.7 million (8.0%) qualified as having ADRD using the 1‐year Bynum‐Standard algorithm and 0.86 million of these patients (32.2%) were newly diagnosed (incident). After adjusting for 31.3% sensitivity and 70.3% PPV of the algorithm the estimated 2019 annual prevalence and incidence of ADRD in the Medicare population aged 65 or older was 18% and 5.8% respectively. When limited to patients with specific AD diagnoses only, 1.0 million prevalent and 0.37 million incident patients were identified resulting in an annual adjusted prevalence and incidence of 6.9% and 2.5% respectively. Prevalence and incidence calculations including adjustments are provided in figure 1.

Conclusion

Using a fit‐for‐purpose validated algorithm, the 2019 annual prevalence and incidence of ADRD in the Medicare population aged 65+ with Part D enrollment was estimated to be 18% and 5.8% respectively.
Stimulation of Cerebral Angiogenesis and Neurogenesis with Transcatheter Intracerebral Laser Photobiomodulation Therapy in Alzheimer’s Disease and Vascular Parkinsonism Aggravated by Dementia
Authors: Maksimovich Ivan V
Published: December 2023

Background

The research is focused on the stimulation of cerebral angiogenesis and neurogenesis using Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT) in patients with dementia in Alzheimer’s disease (AD) and patients with vascular parkinsonism (VP).

Method

The examination of 155 patients included assessment of CDR, The Tomography Dementia Rating scale (TDR), MMSE, cerebral CT, MRI, SG, rheoencephalography (REG) and cerebral MUGA.

85 patients were selected, of whom:

• 48 (30.97%) people suffering from AD, aged 34‐80 (mean age 67.5), men ‐ 17 (35.42%), women ‐ 31 (54.58%). According to dementia severity, patients were subdivided: preclinical stage (TDR‐0) ‐ 4, mild stage (TDR‐1) ‐ 16, moderately severe stage (TDR‐2) ‐ 21, severe stage (TDR‐3) ‐ 7 patients.

• 37 (23.87%) people suffering from VP, aged 58‐80 (mean age 77), men 28 (75.68%), women ‐ 9 (24.32%). 19 (51.35%) had a mild dementia stage (CDR‐1).

In hospital conditions, in a specialized cath lab, all patients underwent Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT) (wavelength 632.8 nanometers).

Result

All 48 (100%) patients with AD underwent angiogenesis stimulation resulting in cerebral collateral capillary revascularization and closure of atreriovenous shunts.

Simultaneously, patients showed a 10‐20% increase in cerebral temporal lobes volume, which indicates cerebral neurogenesis development and tissue regeneration. The process was accompanied by dementia level decrease and cognitive functions restoration. Consequently, patients were transferred to a milder TDR group. Depending on the initial dementia severity, the resulting positive effect was observed from 2 to 15 years.

All 37 (100%) patients with VP underwent angiogenesis stimulation resulting in cerebral microcirculation improvement and cerebral involutive changes decrease, which indicates the neurogenesis development and tissue regeneration. The process was accompanied by decreased dementia and cognitive functions restoration. The resulting positive effect was observed over 10 years.

Conclusion

Despite the differences in AD and VP etiology, Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT) is an effective treatment for dementia in these diseases. The method stimulates angiogenesis and improves blood supply to the brain, it stimulates neurogenesis and the restoration of normal tissue structures, which leads to improved mental and cognitive functions. The resulting effect persists for a long time.
Individuals from Memory Clinic were Associated with Severer Amyloid Deposition in the Chinese Population in Urban Cities
Authors: he kun , Li Binyin , Huang Lin , Zhao Jun , Hua Fengchun , Wang Tao , Li Junpeng , Wang Jie , Wang Mengjie , Huang Qi , Xu Shasha , Chen Ke‐Liang , Ren Shuhua , Cai Huawei , Jiang Donglang , Hu Jingchao , Han xinmin , Guan Yihui , Guo Qihao , Xie Fang
Published: December 2023

Background

Amyloid deposition is considered the initial pathology in Alzheimer’s disease (AD), investigation of amyloid pathology and the risk factor for amyloid pathology and cognitive declines in the Chinese population is critical for personalized management. However, the prevalence of amyloid deposition and the risk factors for amyloid pathology are unknown in the Chinese population.

Method

Participants were recruited from urban communities and memory clinics in Shanghai and Zhengzhou, China. A total of 246 AD individuals, 274 Mild cognitive impairment (MCI) individuals, and 506 Normal cognition (NC) individuals were identified: 106 AD, 156 MCI and 506 NC from the Community‐based cohort (COMC) as well as 140 AD and 118 MCI from the Clinic‐based cohort (CLIC). Amyloid positivity and deposition were analyzed based on amyloid positron emission tomography (PET) scans. We also performed a partial least squares (PLS) analysis to evaluate the associations of cohort, age, sex, education level, and ApoE genotype with amyloid qualification, quantification results and global cognition in all 1026 participants.

Result

Across the two cohorts, the AD group displayed the significantly highest rate of amyloid positivity (211/246, 85.8%), followed by the MCI (122/274, 44.5%) and NC groups (136/506, 26.9%, all P < 0.001). Participants from the CLIC displayed a higher rate of amyloid positivity than those from the COMC in the MCI (68/118, 57.6% vs. 54/156, 34.6%, P < 0.001) and AD groups (128/140, 91.4% vs. 83/106, 78.3%, P = 0.006). MCI (SUVr: 1.37 ± 0.25 vs. 1.25 ± 0.18, P < 0.001), Aβ+ MCI (SUVr: 1.48 ± 0.27 vs. 1.37 ± 0.24, P = 0.03) and AD individuals (SUVr: 1.47 ± 0.23 vs. 1.39 ± 0.23, P = 0.01) in the CLIC displayed significantly greater amyloid deposition than those in the COMC. According to the PLS model, we found that the CLIC was significantly associated with positive amyloid deposition and severer amyloid deposition.

Conclusion

We found that individuals from CLIC displayed a higher amyloid positive rate and severer amyloid deposition. Specifically, in a PLS model, The CLIC, was strongly associated with amyloid pathology.
Longitudinal declines in locus coeruleus integrity are related to worse episodic memory
Authors: Dahl Martin J , Bachman Shelby L , Dutt Shubir , Düzel Sandra , Bodammer Nils C. , Lindenberger Ulman , Kühn Simone , Werkle‐Bergner Markus , Mather Mara
Published: December 2023

Background

Abnormally phosphorylated tau, an indicator of Alzheimer’s disease, starts accumulating in the locus coeruleus (LC), the brain’s major noradrenaline supply, during the first decades of life. Facilitated by technical advances, recent evidence shows that age‐related deficits in noradrenergic neuromodulation impinge on late‐life memory. However, investigations assessing longitudinal locus coeruleus changes and their association with senescent memory are scarce. Moreover, comparisons to other neuromodulatory systems that decline with age are lacking, questioning the specificity of noradrenergic effects.

Method

We collected high‐resolution magnetic resonance imaging (MRI) data of the dopaminergic substantia nigra–ventral tegmental area (SN–VTA) and the noradrenergic locus coeruleus (LC) of 320 younger and older participants of the Berlin Aging Study‐II at two time points (TP1, TP2; ∼1.9 years apart). The imaging protocol included three dedicated scans sensitive to the SN–VTA and LC. We aggregated the information shared across imaging modalities by estimating multimodal latent factors expressing dopaminergic and noradrenergic integrity.

Participants also completed a comprehensive cognitive battery at three time points (TP1–TP3), including tests of fluid intelligence, episodic memory, and working memory. We used structural equation modeling to evaluate cross‐sectional associations of SN–VTA and LC integrity with late‐life cognition. In a second set of models, we probed longitudinal changes in SN–VTA and LC integrity (TP1–TP2) and used them to predict participants’ future cognitive performance (TP3).

Result

Cross‐sectionally, we found differential associations of dopaminergic and noradrenergic nuclei with late‐life cognition. While LC integrity was positively related to better episodic memory across several memory tasks, SN–VTA integrity was positively related to working memory performance. Moreover, consistent with a largely shared biosynthesis of the neuromodulators, dopaminergic and noradrenergic nuclei correlated positively. Longitudinally, we found that older age was associated with more negative change in SN–VTA and LC integrity (TP1–TP2). Importantly, more negative changes in LC integrity reliably predicted worse future episodic memory (at TP3).

Conclusion

These findings support the feasibility of in‐vivo indices for catecholaminergic integrity with potential clinical utility, given the degeneration of both neuromodulatory systems in several age‐associated diseases. Moreover, they highlight differential roles of dopaminergic and noradrenergic neuromodulatory nuclei in late‐life cognitive decline.
Locus coeruleus metabolic changes as a predictor of tau accumulation and cognitive decline
Authors: Koops Elouise A. , Dutta Joyita , Becker Alex , Van Egroo Maxime , Riphagen Joost M. , Hanseeuw Bernard J , Sperling Reisa A. , Fakhri Georges El , Johnson Keith A. , Jacobs Heidi I.L.
Published: December 2023

Background

The locus coeruleus (LC), the primary noradrenergic nucleus in the brainstem, is among the earliest brain structures to accumulate tau pathology, one of the neuropathologic hallmarks of Alzheimer’s disease (AD). Tau pathology in the earlier stages and significant cell loss in the disease’s later stages can affect the metabolic turnover of the LC. In addition, alterations in the LC’s metabolic turnover have been associated with tau formation and propagation. We investigated differences in LC glucose metabolism across AD clinical diagnostic and biomarker groups and its association with longitudinal tau, beta‐amyloid, and cognitive measurements.

Method

We investigated LC FDG‐PET signal of 295 participants from the ADNI‐1 and ADNI‐2/GO cohorts, who were equally distributed across the CSF beta‐amyloid (A) and phosphorylated‐tau (T) biomarker groups (Table 1). An in‐house developed joint‐entropy‐penalized image deblurring algorithm was used to quantify Positron Emission Tomography (PET) signal within small brain regions (Figure 2A). ANCOVA was used to investigate diagnostic and biomarker‐based group differences in LC metabolism. Post‐hoc Tukey contrasts corrected for multiple comparisons in subsequent pairwise analyses. Linear mixed‐effects models investigated the predictive value of LC metabolism on the rate of change in CSF‐based p‐tau, beta‐amyloid and cognitive scores.

Result

Low LC FDG‐PET signal was observed in the amyloid and tau‐positive group compared to the other groups (p<0.0001). Pair‐wise differences between the diagnostic groups did not survive correction for multiple comparisons. Combining biomarker and diagnostic status, we observed lower LC metabolism in A+T+ MCI and AD groups compared to CN and MCI A+T‐ and A‐T‐ groups (p<0.001; Figure 1B). Lower LC metabolism predicted accumulation of p‐tau (t(127) = ‐2.65, p = 0.009) and PACC decline (t(128) = 2.2, p = 0.029; Figure 2). LC metabolism did not significantly predict changes in beta‐amyloid levels or MMSE scores.

Conclusion

This is the first study relating in‐vivo spatially specific measures of LC metabolism to AD‐related biomarker status. Low LC metabolism was most pronounced in those with evidence of underlying AD pathologic change and cognitive impairment. Furthermore, lower LC metabolism predicted greater CSF‐based p‐tau accumulation and declining cognition over time, providing an early marker of AD progression.
Bowel movement frequency, the gut microbiome, and cognitive function in women and men
Authors: Ma Chaoran , Mei Zhendong , Mehta Raaj S , Yuan Changzheng , Kang Jae Hee , Grodstein Francine , Ascherio Alberto , Willett Walter , Chan Andrew T , Huttenhower Curtis , Stampfer Meir J. , Wang Dong D.
Published: December 2023

Background

Bowel movement frequency and the gut microbiome may be associated with the risk of dementia.

Method

We examined the association between bowel movement frequency and cognitive function in 112,753 women and men from Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), and Health Professionals Follow‐Up Study (HPFS) and explored the role of the gut microbiome in explaining these associations in a sub‐cohort of 515 NHSII and HPFS participants. We collected data on bowel movement frequency in 2012/13 and subjective cognitive function from 2014 to 2017 in all participants and objective cognitive function using a neuropsychological battery between 2014 and 2018 in 12,696 NHSII participants. We profiled the gut microbiome using shotgun metagenomics.

Result

Bowel movement frequency was associated with overall objective cognitive function and learning and working memory in an inverse J‐shape dose‐response manner (both Pnon‐linearity<0.05). Compared to those with once daily bowel movements, participants with bowel movement frequency of every 3+ days had significantly worse cognition, equivalent to 3.0 (95% confidence interval (CI),1.2, 4.7) years of additional aging. We observed similar J‐shape dose‐response relationships of bowel movement frequency with the odds of subjective cognitive decline and the likelihood of having more subjective cognitive complaints over time. Bowel movement frequencies of every 3+ days and ≥twice /day, compared to once daily bowel movement, were associated with odds ratios of subjective cognitive decline of 1.73 (95% CI, 1.60, 1.86) and 1.37 (95% CI, 1.33, 1.44), respectively. These relationships were generally consistent across three cohorts and subgroups. Bowel movement frequency and subjective cognition were significantly associated with the overall variation of the gut microbiome (both P <0.005) and specific microbial species. Butyrate producers were depleted in those with less frequent bowel movements and worse cognitive function, while a higher abundance of dysbiosis‐related, pro‐inflammatory species was associated with bowel movement frequency of ≥twice/day and worse cognitive function.

Conclusion

Less frequent bowel movements were associated with worse cognitive function. The gut microbiome may be a mechanistic link underlying the association between intestinal motility patterns and cognitive function.
The impact of modifiable risk factor reduction on future dementia burden: a microsimulation modeling study
Authors: Brück Chiara C. , Wolters Frank J. , Ikram M. Arfan , de Kok Inge M.C.M.
Published: December 2023

Background

Forty percent of dementia cases could potentially be prevented through modifiable risk factors. However, the effect of risk factor reductions might be partially offset by individuals living longer and developing dementia later. Using a microsimulation model, we determined the effect of reductions in smoking and hypertension prevalence on the future dementia burden.

Method

The microsimulation model ‘MISCAN‐Dementia’ was used to simulate life histories and dementia development of 10 million individuals. We modelled mid‐life (40‐59 years) hypertension and late‐life (65+ years) smoking as risk factors (Figure 1), simulating four risk groups: (1) neither risk factor, (2) smoking only, (3) hypertension only, and (4) both risk factors. Sex‐specific population data were used to determine risk factor prevalence. Based on prior literature, smoking and hypertension were each set to a 1.6‐fold increase in dementia risk, and a loss of life expectancy of 4 and 2 years, respectively. Reductions in risk factor prevalence of 100% (i.e. elimination), 50%, 25% and 10% were modeled and evaluated in terms of life years (LYs) without dementia gained, LYs with dementia averted and incident dementia cases averted.

Result

Compared to no reduction, for the lifetime of 1000 individuals, elimination of hypertension results in 360 LYs without dementia gained, 40 LYs with dementia averted and 4 incident cases averted. Although smoking elimination results in 600 LYs without dementia gained, it also causes 75 more dementia LYs and 10 more incident cases. These additional LYs with dementia occur primarily at older ages, due to relatively high life expectancy gains compared to moderate reductions in dementia risk (Figure 2). Reductions of 50%, 25% and 10% result in similar findings at lower magnitudes.

Conclusion

Reductions in prevalence of hypertension and smoking result in a gain in life years free of dementia. However, for smoking this coincides with a (smaller) increase in life years with dementia at older ages. These findings suggest that treatment or prevention of dementia risk factors will generally result in a larger number of cognitively healthy life years, but potentially at the cost of minor increases in years with dementia for risk factors with large effects on survival.