The latest medical research on Dementia

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 dementia gathered by our medical AI research bot.

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Patterns and implications of neurological examination findings in autosomal dominant Alzheimer disease.

Alzheimers & Dementia

As knowledge about neurological examination findings in autosomal dominant Alzheimer disease (ADAD) is incomplete, we aimed to determine the frequency and significance of neurological examination findings in ADAD.

Frequencies of neurological examination findings were compared between symptomatic mutation carriers and non mutation carriers from the Dominantly Inherited Alzheimer Network (DIAN) to define AD neurological examination findings. AD neurological examination findings were analyzed regarding frequency, association with and predictive value regarding cognitive decline, and association with brain atrophy in symptomatic mutation carriers.

AD neurological examination findings included abnormal deep tendon reflexes, gait disturbance, pathological cranial nerve examination findings, tremor, abnormal finger to nose and heel to shin testing, and compromised motor strength. The frequency of AD neurological examination findings was 65.1%. Cross-sectionally, mutation carriers with AD neurological examination findings showed a more than two-fold faster cognitive decline and had greater parieto-temporal atrophy, including hippocampal atrophy. Longitudinally, AD neurological examination findings predicted a significantly greater decline over time.

ADAD features a distinct pattern of neurological examination findings that is useful to estimate prognosis and may inform clinical care and therapeutic trial designs.

Dynamic functional connectivity patterns associated with dementia risk.

Journal Alzheimers Research Therapy

This study assesses the relationships between dynamic functional network connectivity (DFNC) and dementia risk.

DFNC of the default mode (DMN), salience (SN), and executive control networks was assessed in 127 cognitively unimpaired older adults. Stepwise regressions were performed with dementia risk and protective factors and biomarkers as predictors of DFNC.

Associations were found between times spent in (i) a "weakly connected" state and lower self-reported engagement in early- and mid-life cognitive activity and higher LDL cholesterol; (ii) a "SN-negatively connected" state and higher blood pressure, higher depression score, and lower body mass index (BMI); (iii) a "strongly connected" state and higher self-reported engagement in early-life cognitive activity, Preclinical Alzheimer's cognitive composite-5 score, and BMI; and (iv) a "DMN-negatively connected" state and higher self-reported engagement in early- and mid-life stimulating activities and lower LDL cholesterol and blood pressure. The lower number of state transitions was associated with lower brain perfusion.

DFNC states are differentially associated with dementia risk and could underlie reserve.

Plasma neuregulin 1 as a synaptic biomarker in Alzheimer's disease: a discovery cohort study.

Journal Alzheimers Research Therapy

Synaptic dysfunction is an early core feature of Alzheimer's disease (AD), closely associated with cognitive symptoms. Neuregulin 1 (NRG1) is a growth and differentiation factor with a key role in the development and maintenance of synaptic transmission. Previous reports have shown that changes in cerebrospinal fluid (CSF) NRG1 concentration are associated with cognitive status and biomarker evidence of AD pathology. Plasma biomarkers reflecting synaptic impairment would be of great clinical interest.

To measure plasma NRG1 concentration in AD patients in comparison with other neurodegenerative disorders and neurological controls (NC) and to study its association with cerebrospinal fluid (CSF) core AD and synaptic biomarkers.

This retrospective study enrolled 127 participants including patients with AD at mild cognitive impairment stage (AD-MCI, n = 27) and at dementia stage (n = 35), non-AD dementia (n = 26, Aβ-negative), non-AD MCI (n = 19), and neurological controls (n=20). Plasma and CSF NRG1, as well as CSF core AD biomarkers (Aβ 42/Aβ 40 ratio, phospho-tau, and total tau), were measured using ELISA. CSF synaptic markers were measured using ELISA for GAP-43 and neurogranin and through immunoprecipitation mass spectrometry for SNAP-25.

Plasma NRG1 concentration was higher in AD-MCI and AD dementia patients compared with neurological controls (respectively P = 0.005 and P < 0.001). Plasma NRG1 differentiated AD MCI patients from neurological controls with an area under the curve of 88.3%, and AD dementia patients from NC with an area under the curve of 87.3%. Plasma NRG1 correlated with CSF NRG1 (β = 0.372, P = 0.0056, adjusted on age and sex). Plasma NRG1 was associated with AD CSF core biomarkers in the whole cohort and in Aβ-positive patients (β = -0.197-0.423). Plasma NRG1 correlated with CSF GAP-43, neurogranin, and SNAP-25 (β = 0.278-0.355). Plasma NRG1 concentration correlated inversely with MMSE in the whole cohort and in Aβ-positive patients (all, β = -0.188, P = 0.038; Aβ+: β = -0.255, P = 0.038).

Plasma NRG1 concentration is increased in AD patients and correlates with CSF core AD and synaptic biomarkers and cognitive status. Thus, plasma NRG1 is a promising non-invasive biomarker to monitor synaptic impairment in AD.

Differential diagnostic performance of a panel of plasma biomarkers for different types of dementia.

Alzheimers Dementia Amsterdam

We explored what combination of blood-based biomarkers (amyloid beta [Aβ]1-42/1-40, phosphorylated tau [p-tau]181, neurofilament light [NfL], glial fibrillary acidic protein [GFAP]) differentiates Alzheimer's disease (AD) dementia, frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB).

We measured the biomarkers with Simoa in two separate cohorts (n = 160 and n = 152). In one cohort, Aβ1-42/1-40 was also measured with mass spectrometry (MS). We assessed the differential diagnostic value of the markers, by logistic regression with Wald's backward selection.

MS and Simoa Aβ1-42/1-40 similarly differentiated AD from controls. The Simoa panel that optimally differentiated AD from FTD consisted of NfL and p-tau181 (area under the curve [AUC] = 0.94; cohort 1) or NfL, GFAP, and p-tau181 (AUC = 0.90; cohort 2). For AD from DLB, the panel consisted of NfL, p-tau181, and GFAP (AUC = 0.88; cohort 1), and only p-tau181 (AUC = 0.81; cohort 2).

A combination of plasma p-tau181, NfL, and GFAP, but not Aβ1-42/1-40, might be useful to discriminate AD, FTD, and DLB.

Night-to-night variation in sleep associates with day-to-day variation in vigilance, cognition, memory, and behavioral problems in Alzheimer's disease.

Alzheimers Dementia Amsterdam

Sleep disturbances are commonly reported in people living with Alzheimer's disease (AD), but it is currently unknown whether night-to-night variation in sleep predicts day-to-day variation in vigilance, cognition, mood, and behavior (daytime measures).

Subjective and objective sleep and daytime measures were collected daily for 2 weeks in 15 participants with mild AD, eight participants with mild cognitive impairment (MCI), and 22 participants with no cognitive impairment (NCI). Associations between daytime measures and four principal components of sleep (duration, quality, continuity, and latency) were quantified using mixed-model regression.

Sleepiness, alertness, contentedness, everyday memory errors, serial subtraction, and behavioral problems were predicted by at least one of the components of sleep, and in particular sleep duration and continuity. Associations between variations in sleep and daytime measures were linear or quadratic and often different between participants with AD and those with NCI.

These findings imply that daytime functioning in people with AD may be improved by interventions that target sleep continuity.

Subjective cognitive decline and self-reported sleep problems: The SCIENCe project.

Alzheimers Dementia Amsterdam

We aim to investigate the frequency and type of sleep problems in memory clinic patients with subjective cognitive decline (SCD) and their associat...

ADataViewer: exploring semantically harmonized Alzheimer's disease cohort datasets.

Journal Alzheimers Research Therapy

Currently, Alzheimer's disease (AD) cohort datasets are difficult to find and lack across-cohort interoperability, and the actual content of publicly available datasets often only becomes clear to third-party researchers once data access has been granted. These aspects severely hinder the advancement of AD research through emerging data-driven approaches such as machine learning and artificial intelligence and bias current data-driven findings towards the few commonly used, well-explored AD cohorts. To achieve robust and generalizable results, validation across multiple datasets is crucial.

We accessed and systematically investigated the content of 20 major AD cohort datasets at the data level. Both, a medical professional and a data specialist, manually curated and semantically harmonized the acquired datasets. Finally, we developed a platform that displays vital information about the available datasets.

Here, we present ADataViewer, an interactive platform that facilitates the exploration of 20 cohort datasets with respect to longitudinal follow-up, demographics, ethnoracial diversity, measured modalities, and statistical properties of individual variables. It allows researchers to quickly identify AD cohorts that meet user-specified requirements for discovery and validation studies regarding available variables, sample sizes, and longitudinal follow-up. Additionally, we publish the underlying variable mapping catalog that harmonizes 1196 unique variables across the 20 cohorts and paves the way for interoperable AD datasets.

In conclusion, ADataViewer facilitates fast, robust data-driven research by transparently displaying cohort dataset content and supporting researchers in selecting datasets that are suited for their envisioned study. The platform is available at https://adata.scai.fraunhofer.de/ .

Association of the top 20 Alzheimer's disease risk genes with [18F]flortaucipir PET.

Alzheimers Dementia Amsterdam

We previously reported genetic associations of the top Alzheimer's disease (AD) risk alleles with amyloid deposition and neurodegeneration. Here, we report the association of these variants with [18F]flortaucipir standardized uptake value ratio (SUVR).

We analyzed the [18F]flortaucipir scans of 352 cognitively normal (CN), 160 mild cognitive impairment (MCI), and 54 dementia (DEM) participants from Alzheimer's Disease Neuroimaging Initiative (ADNI)2 and 3. We ran step-wise regression with log-transformed [18F]flortaucipir meta-region of interest SUVR as the outcome measure and genetic variants, age, sex, and apolipoprotein E (APOE) ε4 as predictors. The results were visualized using parametric mapping at familywise error cluster-level-corrected P < .05.

APOE ε4 showed significant (P < .05) associations with tau deposition across all disease stages. Other significantly associated genes include variants in ABCA7 in CN, CR1 in MCI, BIN1 and CASS4 in MCI and dementia participants.

We found significant associations to tau deposition for ABCA7, BIN1, CASS4, and CR1, in addition to APOE ε4. These four variants have been previously associated with tau metabolism through model systems.

Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort.

Journal Alzheimers Research Therapy

This work aimed to investigate the potential pathways involved in the association between social and lifestyle factors, biomarkers of Alzheimer's disease and related dementia (ADRD), and cognition.

The authors studied 2323 participants from the Memento study, a French nationwide clinical cohort. Social and lifestyle factors were education level, current household incomes, physical activity, leisure activities, and social network from which two continuous latent variables were computed: an early to midlife (EML) and a latelife (LL) indicator. Brain magnetic resonance imaging (MRI), lumbar puncture, and amyloid-positron emission tomography (PET) were used to define three latent variables: neurodegeneration, small vessel disease (SVD), and AD pathology. Cognitive function was defined as the underlying factor of a latent variable with four cognitive tests. Structural equation models were used to evaluate cross-sectional pathways between social and lifestyle factors and cognition.

Participants' mean age was 70.9 years old, 62% were women, 28% were apolipoprotein-ε4 carriers, and 59% had a Clinical Dementia Rating (CDR) score of 0.5. Higher early to midlife social indicator was only directly associated with better cognitive function (direct β = 0.364 (0.322; 0.405), with no indirect pathway through ADRD biomarkers (total β = 0.392 (0.351; 0.429)). In addition to a direct effect on cognition (direct β = 0.076 (0.033; 0.118)), the association between latelife lifestyle indicator and cognition was also mostly mediated by an indirect effect through lower neurodegeneration (indirect β = 0.066 (0.042; 0.090) and direct β =  - 0.116 (- 0.153; - 0.079)), but not through AD pathology nor SVD.

Early to midlife social factors are directly associated with higher cognitive functions. Latelife lifestyle factors may help preserve cognitive functions through lower neurodegeneration.

Verbal fluency response times predict incident cognitive impairment.

Alzheimers Dementia Amsterdam

In recent decades, researchers have defined novel methods for scoring verbal fluency tasks. In this work, we evaluate novel scores based on speed of word responses.

We transcribed verbal fluency recordings from 641 cases of incident cognitive impairment (ICI) and matched controls, all participants in a large national epidemiological study. Timing measurements of utterances were used to calculate a speed score for each recording. Traditional raw and speed scores were entered into Cox proportional hazards (CPH) regression models predicting time to ICI.

Concordance of the CPH model with speed scores was 0.599, an improvement of 3.4% over a model with only raw scores and demographics. Scores with significant effects included animals raw and speed scores, and letter F speed score.

Novel verbal fluency scores based on response times could enable use of remotely administered fluency tasks for early detection of cognitive decline.

 The current work evaluates prognostication with verbal fluency speed scores. These speed scores improve survival models predicting cognitive decline. Cases with progressive decline have some characteristics suggestive of Alzheimer's disease. The subset of acute decliners is probably pathologically heterogeneous.

Effects of age, amyloid, sex, and APOE ε4 on the CSF proteome in normal cognition.

Alzheimers Dementia Amsterdam

It is important to understand which biological processes change with aging, and how such changes are associated with increased Alzheimer's disease (AD) risk. We studied how cerebrospinal fluid (CSF) proteomics changed with age and tested if associations depended on amyloid status, sex, and apolipoprotein E Ɛ4 genotype.

We included 277 cognitively intact individuals aged 46 to 89 years from Alzheimer's Disease Neuroimaging Initiative, European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery, and Metabolic Syndrome in Men. In total, 1149 proteins were measured with liquid chromatography mass spectrometry with multiple reaction monitoring/Rules-Based Medicine, tandem mass tag mass spectrometry, and SOMAscan. We tested associations between age and protein levels in linear models and tested enrichment for Reactome pathways.

Levels of 252 proteins increased with age independently of amyloid status. These proteins were associated with immune and signaling processes. Levels of 21 proteins decreased with older age exclusively in amyloid abnormal participants and these were enriched for extracellular matrix organization.

We found amyloid-independent and -dependent CSF proteome changes with older age, perhaps representing physiological aging and early AD pathology.

Diagnostic and prognostic performance to detect Alzheimer's disease and clinical progression of a novel assay for plasma p-tau217.

Journal Alzheimers Research Therapy

Recent advances in disease-modifying treatments highlight the need for accurately identifying individuals in early Alzheimer's disease (AD) stages and for monitoring of treatment effects. Plasma measurements of phosphorylated tau (p-tau) are a promising biomarker for AD, but different assays show varying diagnostic and prognostic accuracies. The objective of this study was to determine the clinical performance of a novel plasma p-tau217 (p-tau217) assay, p-tau217+Janssen, and perform a head-to-head comparison to an established assay, plasma p-tau217Lilly, within two independent cohorts. METHODS: The study consisted of two cohorts, cohort 1 (27 controls and 25 individuals with mild-cognitive impairment [MCI]) and cohort 2 including 147 individuals with MCI at baseline who were followed for an average of 4.92 (SD 2.09) years. Receiver operating characteristic analyses were used to assess the performance of both assays to detect amyloid-β status (+/-) in CSF, distinguish MCI from controls, and identify subjects who will convert from MCI to AD dementia. General linear and linear mixed-effects analyses were used to assess the associations between p-tau and baseline, and annual change in Mini-Mental State Examination (MMSE) scores. Spearman correlations were used to assess the associations between the two plasma measures, and Bland-Altmann plots were examined to assess the agreement between the assays.

Both assays showed similar performance in detecting amyloid-β status in CSF (plasma p-tau217+Janssen AUC = 0.91 vs plasma p-tau217Lilly AUC = 0.89), distinguishing MCI from controls (plasma p-tau217+Janssen AUC = 0.91 vs plasma p-tau217Lilly AUC = 0.91), and predicting future conversion from MCI to AD dementia (plasma p-tau217+Janssen AUC = 0.88 vs p-tau217Lilly AUC = 0.89). Both assays were similarly related to baseline (plasma p-tau217+Janssen rho = -0.39 vs p-tau217Lilly rho = -0.35), and annual change in MMSE scores (plasma p-tau217+Janssenr = -0.45 vs p-tau217Lillyr = -0.41). Correlations between the two plasma measures were rho = 0.69, p < 0.001 in cohort 1 and rho = 0.70, p < 0.001 in cohort 2. Bland-Altmann plots revealed good agreement between plasma p-tau217+Janssen and plasma p-tau217Lilly in both cohorts (cohort 1, 51/52 [98%] within 95%CI; cohort 2, 139/147 [95%] within 95%CI).

Taken together, our results indicate good diagnostic and prognostic performance of the plasma p-tau217+Janssen assay, similar to the p-tau217Lilly assay.