The latest medical research on Alzheimers

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about alzheimers gathered by our medical AI research bot.

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Effect of reduction in brain amyloid levels on change in cognitive and functional decline in randomized clinical trials: An instrumental variable meta-analysis.

Alzheimers & Dementia

Whether the reduction in brain amyloid beta (Aβ) plaque alone may substantially slow cognitive and functional decline in patients with dementia or mild cognitive impairment due to Alzheimer's disease (AD) remains debated.

An instrumental variable meta-analysis was performed to infer the effect of change in positron emission tomography (PET)-measured Aβ standardized uptake value ratio (SUVR) on cognitive and functional decline.

Pooling data from 16 randomized trials demonstrates that each 0.1-unit decrease in PET Aβ SUVR is associated with a reduction (95% confidence interval) by 0.09 (0.034-0.15), 0.33 (0.12-0.55), and 0.13 (0.017-0.24) point in the average change of the Clinical Dementia Rating-Sum of Boxes, the Alzheimer's Disease Assessment Scale-Cognitive Subscale, and the Mini-Mental State Examination, respectively.

A widely cited meta-analysis article concluded amyloid beta reduction does not substantially improve cognition. We identified data inconsistencies in the initial publication and found new trial data. We repeated the meta-analysis after correcting data inconsistencies and adding new trial data. Updated results suggested statistically significant clinical benefit of amyloid beta reduction. Amyloid beta is a viable biological target for the treatment and prevention of AD.

Global, regional, and national trends of dementia incidence and risk factors, 1990-2019: A Global Burden of Disease study.

Alzheimers & Dementia

An ample literature documents the growing prevalence of dementia and associated costs. Less attention has been paid to decreased dementia incidence in some countries.

We analyzed trends in age-standardized dementia, stroke, and ischemic heart disease (the triple threat) incidence rates and population attributable fraction of death and disability attributable to 12 risk factors in 204 countries and territories and 51 regions using Global Burden of Disease 2019 data.

During 1990 to 2019, dementia incidence declined in 71 countries; 18 showed statistically significant declines, ranging from -12.1% (95% uncertainty intervals -16.9 to -6.8) to -2.4% (-4.6 to -0.5). During 2010 to 2019, 16 countries showed non-significant declines. Globally, the burden of the triple threat attributable to air pollution, dietary risks, non-optimal temperature, lead exposure, and tobacco use decreased from 1990 to 2019.

The declining incidence of dementia in some countries, despite growing prevalence, is encouraging and urges further investigation.

Implications of preclinical Alzheimer's disease biomarker disclosure for US policy and society.

Alzheimers Dementia Amsterdam

Disclosure of Alzheimer's disease (AD) biomarkers to cognitively unimpaired adults are currently conducted only in research settings. Yet, US Food ...

TREM2 Gene Compound Heterozygosity in Neurodegenerative Disorders.

Journal of Alzheimer's Disease

Homozygous variants of the TREM2 and TYROBP genes have been shown to be causative for multiple bone cysts and neurodegeneration leading to progressive dementia (NHD, Nasu-Hakola disease).

To determine if biallelic variants of these genes and/or oligogenic inheritance could be responsible for a wider spectrum of neurodegenerative conditions.

We analyzed 52 genes associated with neurodegenerative disorders using targeted next generation sequencing in a selected group of 29 patients (n = 14 Alzheimer's disease, n = 8 frontotemporal dementia, n = 7 amyotrophic lateral sclerosis) carrying diverse already determined rare variants in exon 2 of TREM2. Molecular modeling was used to get an insight into the potential effects of the mutation.

We identified a novel mutation c.401_406delinsTCTAT; p.(Asp134Valfs*55) in exon 3 of TREM2 in an Alzheimer's disease patient also carrying the p.Arg62His TREM2 variant. Molecular modeling revealed that the identified mutation prevents anchoring of the TREM2 protein in the membrane, leaving the core of the Ig-like domain intact.

Our results expand the spectrum of neurodegenerative diseases, where the carriers of biallelic mutations in TREM2 have been described for Alzheimer's disease, and highlight the impact of variant burden in other genes on phenotypic heterogeneity.

Acceptability and Preliminary Effectiveness of a Remote Dementia Educational Training Among Primary Care Providers and Health Navigators.

Journal of Alzheimer's Disease

Optimal care can improve lives of families with dementia but remains under-implemented. Most healthcare professional training is in person, time-intensive, and does not focus on key aspects such as early detection, and cultural competency.

We explored the acceptability and preliminary effectiveness of a training, The Dementia Update Course, which addressed these issues. We hypothesized that the training would lead to increased levels of perceived dementia care competency among key healthcare workers, namely primary care providers (PCPs) and health navigators (HNs).

We conducted pre-post training assessments among 22 PCPs and 32 HNs. The 6.5-h training was remote, and included didactic lectures, case discussion techniques, and materials on dementia detection and care. Outcomes included two 5-point Likert scales on acceptability, eleven on perceived dementia care competency, and the three subscales of the General Practitioners Confidence and Attitude Scale for Dementia. We used paired samples t-tests to assess the mean differences in all preliminary effectiveness outcomes.

The training included 28.6% of PCPs and 15.6% of HNs that self-identified as non-White or Latino and 45.5% of PCPs and 21.9% of HNs who served in rural areas. PCPs (84.2%) and HNs (91.7%) reported a high likelihood to recommend the training and high satisfaction. Most preliminary effectiveness outcomes analyzed among PCPs (11/14) and all among HNs (8/8) experienced an improvement from pre- to post-training (p <  0.05).

A relatively brief, remote, and inclusive dementia training was associated with high levels of acceptability and improvements in perceived dementia care competency among PCPs and HNs.

Neuropathological and Clinical Correlates of Lewy Body Disease Survival by Race and Ethnicity in the National Alzheimer's Coordinating Center.

Journal of Alzheimer's Disease

Survival and associated clinical and pathological characteristics in Lewy body disease (LBD)-related dementias are understudied. Available studies focus primarily on white non-Hispanic samples.

We investigated demographic, clinical, and pathological correlates of survival by race and ethnicity in an autopsy-confirmed cohort of LBD cases.

Using National Alzheimer's Coordinating Center data, we selected participants who self-identified as Black, Hispanic, or white who had neuropathological assessments showing transitional or diffuse LBD pathology. We used Kruskal-Wallis and Pearson χ2 analyses to investigate group differences in demographic and presenting clinical and pathological characteristics. We used linear regressions to identify predictors of survival with sex, age at symptom onset, education, ethnoracial status, LBD pathology type, and Braak tangle stage included in the model.

Data from 1,441 white, 60 Black, and 54 Hispanic participants were available for analysis. Hispanics were more likely to have transitional LBD pathology and had a longer survival than white and Black participants. After controlling for demographic and pathological variables, length of survival did not differ between Hispanics and Black or white participants. Additional key findings demonstrated discrepancies between clinical diagnoses received at last visit and pathological findings, particularly among Black participants.

LBD survival differences by race and ethnicity can be accounted for by LBD pathology type and co-occurring Alzheimer's disease pathology. The discrepancies between clinical diagnoses and pathological findings raise concern that dementia with Lewy bodies is underdiagnosed in NACC, especially for Black older adults.

Circulating Cell-Free Genomic DNA Is Associated with an Increased Risk of Dementia and with Change in Cognitive and Physical Function.

Journal of Alzheimer's Disease

Altered cell homeostasis, seen in cognitive decline and frailty, leads to cell death and turnover, releasing circulating cell-free DNA (ccf-DNA).

The goal of this study is to determine if serum genomic cell-free DNA (ccf-gDNA) is associated with physical and cognitive decline in older adults.

We used serum from 631 community-dwelling individuals from the Religious Orders Study or Rush Memory and Aging Project who were without cognitive impairment at baseline. ccf-gDNA fragments in serum were quantified using digital PCR. An array of cognitive and physical traits, risk of dementia, global cognition, and frailty at or nearest the time of blood draw were regressed on ccf-DNA, with adjustment for age, sex, race, and education.

Cross-sectionally, higher ccf-gDNA levels were associated with lower global cognition score and slower gait speed at the evaluation nearest to blood draw. Higher ccf-gDNA levels were associated with increased odds of incident dementia (OR 1.27, 95% CI 1.05, 1.54). Longitudinally, higher levels of ccf-gDNA were associated with steeper general cognitive decline and worsening frailty over eight years of follow up.

This study demonstrates that ccf-gDNA fragments have utility for identifying persons at higher risk of developing dementia and worsening cognition and frailty.

Hypnosis Intervention for Couples Confronted with Alzheimer's Disease: Promising Results of a First Exploratory Study.

Journal of Alzheimer's Disease

Dementia has a negative impact on the quality of life of the person with dementia and their spouse caregivers, as well as on the couple's relationship, which can lead to high levels of distress for both partners. Hypnosis has been shown to be effective in managing distress and increasing the quality of the relationship.

The aim was to develop a standardized hypnosis intervention for couples confronted with Alzheimer's disease and evaluate its feasibility, acceptability, and helpfulness in managing the distress of both partners and increasing the quality of the relationship.

In a single-arm study, sixteen couples received the 8-week intervention. Qualitative and quantitative assessments were conducted pre- and post-intervention as well as three months after.

88.9% of couples (n = 16) of the final sample (n = 18) completed the intervention. Despite the negative representations of hypnosis, several factors led couples to accept to participate in this study: positive expectations, professional endorsement, medical application, non-drug approach, home-based, free, flexible, and couple-based intervention. The results showed a significant decrease in distress for both partners. These effects were maintained three months after the intervention. Couples felt more relaxed, had fewer negative emotions, accepted difficulties more easily, were more patient, and reported better communication and more affection in the relationship.

Overall, this pilot study shows the feasibility and acceptability of hypnosis with couples confronted with Alzheimer's disease. Although measures of the preliminary pre- and post-intervention effects are encouraging, confirmatory testing with a randomized controlled trial is needed.

Antimicrobial, Polarizing Light, and Paired Helical Filament Properties of Fragmented Tau Peptides of Selected Putative Gingipains.

Journal of Alzheimer's Disease

Tau is an established substrate for gingipains secreted by Porphyromonas gingivalis. Hyperphosphorylation of tau and neurofibrillary tangle (NFT) formation is a defining lesion of Alzheimer's disease (AD) where NFT distribution is related to Braak stage and disease severity.

To assess gingipains'-fragmented tau peptides for their antimicrobial properties and for the likelihood of paired helical/straight filament (PHF/SF) formation with implications for the NFT lesion.

Seven non-phosphorylated (A-G) and three phosphorylated (A-C) tau peptides, were tested for antimicrobial properties against P. gingivalis. Polarizing light properties were determined using Congo Red staining. Secondary and tertiary structures of peptides B-F were determined using transmission electron microscopy (TEM) and circular dichroism (CD) was undertaken for the soluble peptides A in phosphorylated and non-phosphorylated states.

Phosphorylated tau peptide A displayed a significant effect against planktonic P. gingivalis. The CD results demonstrated that both peptides A, in phosphorylated and non-phosphorylated states, in aqueous solution, adopted mainly β-type structures. Non-phosphorylated peptides B-F and phosphorylated peptides B-C were insoluble and fibrillar under the TEM. The secondary and tertiary structures of the non-phosphorylated peptide B demonstrated fewer helical twists, whereas peptide C displayed significantly more helical twists along the whole fiber(s) length following its phosphorylation.

Phosphorylated peptide A reduced P. gingivalis viability. CD spectroscopy demonstrated the phosphorylated and the non-phosphorylated peptide A predominantly formed from β-sheet structures in aqueous solution with potential antimicrobial activity. Phosphorylation of tau peptides physically changed their tertiary structure into PHFs with potential for self-aggregation and binding to the NFT lesion.

Glucometabolic Changes Are Associated with Structural Gray Matter Alterations in Prodromal Dementia.

Journal of Alzheimer's Disease

Glucometabolic changes, such as high glycemic load (GL) diet and insulin resistance (IR), are potential risk factor of Alzheimer's disease (AD). Yet, the effect of these factors on brain alterations that contribute to AD pathology has not been clearly demonstrated.

We aimed to assess the relationship of GL and IR with gray matter volumes involved in prodromal dementia.

GL and Triglyceride-Glucose (TyG) index, an IR surrogate marker, were calculated in 497 participants who underwent magnetic resonance imaging (MRI). The gray matter volumes most related to prodromal dementia/mild cognitive impairment (diagnosed in 18/158 participants during the 7-year follow-up) were identified using a data-driven machine learning algorithm.

Higher GL diet was associated with reduced amygdala volume. The TyG index was negatively associated with the hippocampus, amygdala, and putamen volumes.

These results suggest that GL and IR are associated with lower gray matter volumes in brain regions involved in AD pathology.

Neurotoxicity of Diesel Exhaust Particles.

Journal of Alzheimer's Disease

Air pollution particulate matter (PM) is strongly associated with risks of accelerated cognitive decline, dementia and Alzheimer's disease. Ambient PM batches have variable neurotoxicity by collection site and season, which limits replicability of findings within and between research groups for analysis of mechanisms and interventions. Diesel exhaust particles (DEP) offer a replicable model that we define in further detail.

Define dose- and time course neurotoxic responses of mice to DEP from the National Institute of Science and Technology (NIST) for neurotoxic responses shared by DEP and ambient PM.

For dose-response, adult C57BL/6 male mice were exposed to 0, 25, 50, and 100μg/m3 of re-aerosolized DEP (NIST SRM 2975) for 5 h. Then, mice were exposed to 100μg/m3 DEP for 5, 100, and 200 h and assayed for amyloid-β peptides, inflammation, oxidative damage, and microglial activity and morphology.

DEP exposure at 100μg/m3 for 5 h, but not lower doses, caused oxidative damage, complement and microglia activation in cerebral cortex and corpus callosum. Longer DEP exposure for 8 weeks/200 h caused further oxidative damage, increased soluble Aβ, white matter injury, and microglial soma enlargement that differed by cortical layer.

Exposure to 100μg/m3 DEP NIST SRM 2975 caused robust neurotoxic responses that are shared with prior studies using DEP or ambient PM0.2. DEP provides a replicable model to study neurotoxic mechanisms of ambient PM and interventions relevant to cognitive decline and dementia.

Evaluating the Bidirectional Causal Association Between Daytime Napping and Alzheimer's Disease Using Mendelian Randomization.

Journal of Alzheimer's Disease

Until now, both cross-sectional and longitudinal studies have identified controversial findings about the association between daytime napping and Alzheimer's disease (AD) or cognitive decline. Therefore, it remains unclear about the causal association between daytime napping and AD or cognitive decline.

We aim to investigate the causal association between daytime napping and AD.

Here, we conduct a bidirectional Mendelian randomization (MR) analysis to investigate the causal association between daytime napping and AD using large-scale GWAS datasets from daytime napping including 452,633 individuals of European ancestry and AD including 35,274 AD and 59,163 controls of European ancestry. A total of five MR methods are selected including inverse-variance weighted (IVW), weighted median, MR-Egger, MR-PRESSO, and contamination mixture method.

MR analysis highlights significant causal association of AD with daytime napping using IVW (beta = -0.006, 95% CI [-0.009, -0.002], p = 2.00E-03), but no significant causal association of daytime napping with AD using IVW (OR = 0.76, 95% CI 0.53-1.10, p = 1.40E-01).

Our bidirectional MR analysis demonstrates the causal effect of AD on daytime napping. However, there is no causal effect of daytime napping on AD. Our current findings are consistent with recent evidence from other MR studies that highlight little evidence supporting a causal effect of sleep traits on AD and support the causal effect of AD on sleep traits.