Alzheimer's Disease In Adults Research Articles

Cortical activation in elderly patients with Alzheimer's disease dementia during working memory tasks: a multichannel fNIRS study.

This study aimed to investigate cortical activation and functional connectivity in the cortex during working memory (WM) tasks in patients with Alzheimer's disease (AD) using functional near-infrared spectroscopy (fNIRS). A total of 17 older adults with AD and 17 cognitively normal (CN) participants were recruited. fNIRS was utilized to monitor oxygenated hemoglobin (HbO) concentrations in the frontotemporal lobe, while participants performed WM tasks to examine WM impairments in subjects with AD. Student's t-test for continuous variables and the chi-square test for categorical variables were used to compare the clinical and HbO variables between the AD and CN groups. Functional connectivity was analyzed using Pearson's correlation coefficient between the time series of each channel-to-channel pair. The changes in HbO concentrations and cortical activations during the WM task showed that the HbO concentration curve of the CN group was higher than that of the AD group during the encoding and maintenance phases of the WM task. Although in the brain region scale, there were no significant differences in average HbO concentrations between the two groups, many channels located in the frontal and temporal lobes showed significant differences (p < 0.05) in the average HbO (channels 7 and 32) and slope HbO values (channels 7, 8, 9, 23, 30, 34, and 38) during the WM task. The average functional connectivity of the AD group was significantly lower than that of the CN group (p < 0.05). The functional connectivity was stronger in the frontopolar (FP) region than in other areas in both groups. This study revealed there were significant differences in HbO concentration in older adult patients with AD compared to CN during the WM task. The characteristics of HbO measured by the fNIRS technique can be valuable for distinguishing between AD and CN in older adults.

Preliminary reference values for Alzheimer's disease plasma biomarkers in Congolese individuals with and without Alzheimer's disease.

Western countries have provided reference values (RV) for Alzheimer's disease (AD) plasma biomarkers, but there are not available in Sub-Saharan African populations. We provide preliminary RV for AD and other plasma biomarkers including amyloid- β (Aβ42/40), phosphorylated tau-181 and 217 (p-tau181, p-tau217), neurofilament light (Nfl), glial fibrillary acidic protein (GFAP), interleukin 1b and 10 (IL-1b and IL-10) and tumor necrosis factor α (TNFα) in Congolese adults with and without dementia. 85 adults (40 healthy and 45 dementia) over 50 years old were included. Blood samples were provided for plasma AD biomarkers Aβ42/40 and p-tau181, p-tau217; Nfl and GFAP; IL-1b and IL-10 and TNFα analyzed using SIMOA. Linear and logistic regressions were conducted to evaluate differences in biomarkers by age and gender and neurological status, and for the prediction of dementia status by each individual biomarker. RV were those that optimized sensitivity and specificity based on Youden's index. In this sample of 85 adults, 40 (47%) had dementia, 38 (45.0%) were male, overall mean age was 73.2 (SD 7.6) years with 8.3 (5.4) years of education. There were no significant differences in age, gender, and education based on neurological status. Biomarker concentrations did not significantly differ by age except for p-tau181 and GFAP and did not differ by sex. Preliminary cutoffs of various plasma in pg/ml were 0.061 for Aβ42/40, 4.50 for p-tau 181, 0.008 for p-tau 217, 36.5 for Nfl, 176 for GFAP, 1.16 for TNFa, 0.011 for IL-1b, and 0.38 for IL-10. All AUCs ranged between 0.64-0.74. P-tau 217 [0.74 (0.61, 0.86)] followed by GFAP [0.72 (0.61, 0.83), and Nfl [0.71 (0.60, 0.82)] had the highest AUC compared to other plasma biomarkers. This study provides RV which could be of preliminary utility to facilitate the screening, clinical diagnostic adjudication, classification, and prognosis of AD in Congolese adults.

Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: The MIND-China study.

Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-β (Aβ), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p<0.05). CMM was significantly associated with increased plasma Aβ40, Aβ42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.

Association between Alzheimer's disease and Toxocara infection/exposure: a case-control study.

Infections may contribute to Alzheimer's disease (AD) risk. Limited evidence suggests Toxocara spp. infection/exposure could influence AD development. We investigated Toxocara seropositivity and AD in Iranian adults using a matched case-control study. Our sample included 90 AD cases and 91 healthy older adults. Anti-Toxocara immunoglobulin G (IgG) antibodies were assessed via enzyme-linked immunosorbent assay. We computed the odds ratios (ORs) and 95% confidence intervals (CIs) through univariable and multivariable analyses, adjusting for potential confounders. There were 33/90 (36.67% [95% CI 26.75 to 47.48]) anti-Toxocara IgG seropositive individuals identified among the AD cases and 21/91 (23.07% [95% CI 14.89 to 33.09]) among the healthy controls. In univariable analysis, a significant association was identified between anti-Toxocara IgG seropositivity and AD (OR 1.93 [95% CI 1.01 to 3.69], p<0.001). Moreover, the association remained significant (OR 2.18 [95% CI 1.05 to 4.49], p<0.001) in multivariable analysis after adjustment for covariates. There was no association between anti-Toxocara IgG seropositivity and the severity of AD (OR 0.75 [95% CI 0.21 to 2.61], p=0.47). Our findings indicated that Toxocara exposure/infection could be a potential risk factor for development of AD. To better understand a real causality between Toxocara exposure/infection and AD and related dementias, follow-up designed and adequately powered studies are needed.

Dementia in Rare Genetic Neurodevelopmental Disorders: A Systematic Literature Review.

Knowledge of young-onset Alzheimer disease in adults with Down syndrome has greatly improved clinical care. However, little is known about dementia in rare genetic neurodevelopmental disorders (RGNDs). In this review, a comprehensive overview is provided of reports on dementia and cognitive/adaptive trajectories in adults with RGNDs. A systematic literature review was conducted in Embase, Medline ALL, and PsycINFO on December 6, 2022. The protocol was registered in PROSPERO (CRD42021223041). Search terms for dementia, cognitive and adaptive functioning, and RGNDs were combined using generic terms and the Orphanet database. Study characteristics and descriptive data on genetic diagnosis, clinical and neuropathologic features, comorbidities, and diagnostic methods were extracted using a modified version of the Cochrane Data Extraction Template. The literature search yielded 40 publications (17 cohorts, 23 case studies) describing dementia and/or cognitive or adaptive trajectories in adults with 14 different RGNDs. Dementia was reported in 49 individuals (5 cohorts, 20 cases) with a mean age at onset of 44.4 years. Diagnostics were not disclosed for half of the reported individuals (n = 25/49, 51.0%). A total of 44 different psychodiagnostic instruments were used. MRI was the most reported additional investigation (n = 12/49, 24.5%). Comorbid disorders most frequently associated with cognitive/adaptive decline were epilepsy, psychotic disorders, and movement disorders. Currently available literature shows limited information on aging in RGNDs, with relatively many reports of young-onset dementia. Longitudinal data may provide insights into converging neurodevelopmental degenerative pathways. We provide recommendations to optimize dementia screening, diagnosis, and research.

Protective role of Bacillus Calmette–Guérin vaccine in Alzheimer's disease progression: A systematic review and meta-analysis

Introduction: Alzheimer's disease (AD) represents a significant societal challenge, highlighting the need to explore effective prevention and treatment approaches. Recent literature has suggested that Bacillus Calmette-Guérin (BCG) vaccine may be a viable therapeutic option for immune disorders associated with AD due to its immunomodulatory properties and protection against various diseases. MethodsThis systematic review aimed to evaluate the association of BCG vaccine in the prevention of AD using six medical-scientific databases. A meta-analytical approach was undertaken to estimate the risk of AD incidence in patients with and without BCG vaccine exposure, followed by subgroup analyses. A risk of bias (RoB) assessment was performed using the Newcastle-Ottawa Scale (NOS). ResultsSix cohort studies meeting our inclusion criteria were included (47,947 participants) in the study. From our meta-analysis, intravesical BCG vaccine administration lowered the risk of incidence of AD by 26% in non-muscle-invasive bladder cancer (p < 0.00001). Subgroup analyses showed that BCG vaccination showed a potentially notable preventive effect on AD in older adults (>75 years) and female participants. Conversely, significant heterogeneity in results was observed among male participants and those aged <75 years. The RoB was low in three studies and unclear in the remaining studies. ConclusionsAlthough our results support the potential benefits of BCG vaccine in preventing AD in specific demographics, we remain cautious about interpreting such results. Further research examining the implications of BCG vaccination for prevention and possible treatment of AD should be undertaken in the future.

Alzheimer’s disease susceptibility in African American elders: a classification and regression tree (CART) analysis approach

Alzheimer's disease (AD) is increasingly prevalent, especially among African American older adults. Despite its widespread nature, accurate and timely diagnosis of AD remains challenging. Addressing the research gap in sociodemographic and cardiovascular risk factor research associated with AD in African American older adults, this study aimed to identify and analyze distinct subgroups within this population that are particularly vulnerable to AD, thereby contributing to the development of targeted interventions and healthcare strategies. This study employs a rigorous methodology utilizing classification and regression tree (CART) analysis to examine data from the 2017 Uniform Data Set (UDS). This approach enables a nuanced analysis of AD susceptibility among African American older adults. The CART analysis revealed significant associations between the studied sociodemographic and cardiovascular risk factors and AD susceptibility among African American older adults. The results indicate the presence of specific subgroups with increased vulnerability to AD, shaped by varying levels of education [relative importance (RI): 100%], antidepressant usage (RI: 83.1%), BMI (RI: 71.2%), use of antipsychotic agents (RI: 35.5%), and age of smoking cessation (RI: 21.5%). These findings underscore the importance of culturally specific research and interventions for addressing AD among African Americans. This study's findings, revealing significant associations between sociodemographic and cardiovascular risk factors and AD susceptibility among African American older adults, underscore the necessity of developing healthcare policies and interventions specifically tailored to address these risks.

Voxel-based dysconnectomic brain morphometry with computed tomography in Down syndrome.

Alzheimer's disease (AD) is a major health concern for aging adults with Down syndrome (DS), but conventional diagnostic techniques are less reliable in those with severe baseline disability. Likewise, acquisition of magnetic resonance imaging to evaluate cerebral atrophy is not straightforward, as prolonged scanning times are less tolerated in this population. Computed tomography (CT) scans can be obtained faster, but poor contrast resolution limits its function for morphometric analysis. We implemented an automated analysis of CT scans to characterize differences across dementia stages in a cross-sectional study of an adult DS cohort. CT scans of 98 individuals were analyzed using an automatic algorithm. Voxel-based correlations with clinical dementia stages and AD plasma biomarkers (phosphorylated tau-181 and neurofilament light chain) were identified, and their dysconnectomic patterns delineated. Dementia severity was negatively correlated with gray (GM) and white matter (WM) volumes in temporal lobe regions, including parahippocampal gyri. Dysconnectome analysis revealed an association between WM loss and temporal lobe GM volume reduction. AD biomarkers were negatively associated with GM volume in hippocampal and cingulate gyri. Our automated algorithm and novel dysconnectomic analysis of CT scans successfully described brain morphometric differences related to AD in adults with DS, providing a new avenue for neuroimaging analysis in populations for whom magnetic resonance imaging is difficult to obtain.

Memory performance mediates subjective sleep quality associations with cerebrospinal fluid Alzheimer's disease biomarker levels and hippocampal volume among individuals with mild cognitive symptoms.

Sleep disturbances are prevalent in Alzheimer's disease (AD), affecting individuals during its early stages. We investigated associations between subjective sleep measures and cerebrospinal fluid (CSF) biomarkers of AD in adults with mild cognitive symptoms from the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study, considering the influence of memory performance. A total of 442 participants aged >50 years with a Clinical Dementia Rating (CDR) score of 0.5 completed the Pittsburgh Sleep Quality Index questionnaire and underwent neuropsychological assessment, magnetic resonance imaging acquisition, and CSF sampling. We analysed the relationship of sleep quality with CSF AD biomarkers and cognitive performance in separated multivariate linear regression models, adjusting for covariates. Poorer cross-sectional sleep quality was associated with lower CSF levels of phosphorylated tau and total tau alongside better immediate and delayed memory performance. After adjustment for delayed memory scores, associations between CSF biomarkers and sleep quality became non-significant, and further analysis revealed that memory performance mediated this relationship. In post hoc analyses, poorer subjective sleep quality was associated with lesser hippocampal atrophy, with memory performance also mediating this association. In conclusion, worse subjective sleep quality is associated with less altered AD biomarkers in adults with mild cognitive symptoms (CDR score 0.5). These results could be explained by a systematic recall bias affecting subjective sleep assessment in individuals with incipient memory impairment. Caution should therefore be exercised when interpreting subjective sleep quality measures in memory-impaired populations, emphasising the importance of complementing subjective measures with objective assessments.

Development of a Cognitive Composite for Preclinical Alzheimer's Disease in Korean Older Adults.

As tracking subtle cognitive declines in the preclinical stage of Alzheimer's disease (AD) is difficult with traditional individual outcome measures, need for cognitive composite for preclinical AD is widely recognized. We aimed to develop culturally appropriate cognitive composite that sensitively identifies subtle cognitive decline of preclinical AD in Korean older adults. A total 225 cognitively normal elderly individuals from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, were included. Tests of episodic memory, orientation, and executive function were carefully selected through review of previously established composites. Three candidate composites including Consortium to Establish a Registry for Alzheimer's Disease Word list recall (WLR), Logical memory (LM) II, and Mini-Mental status examination (MMSE) in common, and Letter fluency test (LF), category fluency test, or Stroop color and word test, were selected. Student t-tests demonstrated that only the composite composed of WLR, LM II, MMSE, and LF (Composite 1) showed a significant difference in score decline over two-year follow-up period between Aβ positive and negative group (p = 0.03). Linear mixed model analyses also showed that the Aβ x time interaction effect was significant only for Composite 1 (p = 0.025). Based on the results, Composite 1 was chosen as the final cognitive composite for preclinical Alzheimer's disease (CPAD). CPAD can be used to assess subtle cognitive decline of preclinical AD in clinical research settings, especially in Korean older adults. It also may be used for monitoring progression or treatment benefits in clinical practices.

Prevalence of Alzheimer's disease dementia in the 50 US states and 3142 counties: A population estimate using the 2020 bridged-race postcensal from the National Center for Health Statistics.

This study estimates the prevalence and number of people living with Alzheimer's disease (AD) dementia in 50 US states and 3142 counties. We used cognitive data from the Chicago Health and Aging Project, a population-based study, and combined it with the National Center for Health Statistics 2020 bridged-race population estimates to determine the prevalence of AD in adults ≥65 years. A higher prevalence of AD was estimated in the east and southeastern regions of the United States, with the highest in Maryland (12.9%), New York (12.7%), and Mississippi (12.5%). US states with the highest number of people with AD were California, Florida, and Texas. Among larger counties, those with the highest prevalence of AD were Miami-Dade County in Florida, Baltimore city in Maryland, and Bronx County in New York. The state- and county-specific estimates could help public health officials develop region-specific strategies for caring for people with AD.

Tropospheric formaldehyde levels infer ambient formaldehyde-induced brain diseases and global burden in China, 2013–2019

Although air pollutions cause human diseases, no epidemiological study has investigated the effect of exposure to air pollutants on brain diseases in the general population. Our objective was to examine the association between tropospheric airborne pollutants and human health risk and global burden, especially, attributable to indoor formaldehyde (FA) pollution in China. The data of tropospheric pollutants, such as: CO, NO, O3, PM2.5 or PM10, SO2, and FA in China, 2013–2019, which were derived from the database of satellite remote-sensing, were first calculated and then analyzed them according to satellite cloud pictures. The rate of prevalence, incidence, deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) of the Chinese population was obtained from the Global Burden of Diseases (GBD 2010). A linear regression analysis was used to evaluate the relationship between tropospheric FA concentrations and GBD indexes of human brain diseases, the numbers of fire plot, the average summer temperature, population density and car sales in China from 2013 to 2019. Our results showed that the levels of tropospheric FA could reflect the degree of indoor air FA pollution on a nationwide scale in China; in particular, only tropospheric FA exhibited a positive correlation with the rates of both prevalence and YLDs in brain diseases including: Alzheimer's disease (AD) and brain cancer, but not in Parkinson's disease and depression. In particular, the spatial-temporal changes in tropospheric FA levels were consistent with the geographical distribution of FA exposure-induced AD and brain cancer in both sex old adults with age (60–89). In addition, summer average temperature, car sales and population density were positively correlated with tropospheric FA levels in China, 2013–2019. Hence, mapping of tropospheric pollutants could be used for air quality monitoring and health risk assessment.

Apolipoprotein E ε4 Modifies the Effect of Possible Anticholinergic Drugs on Incident Dementia: The Shanghai Aging Study.

To validate the hypothesis that apolipoprotein E (APOE) ε4 modifies the effect of possible anticholinergic drugs (PACDs) on incident dementia among older adults. A population-based prospective study. Dementia-free older adults in an urban community in Shanghai, China. At baseline, PACDs were defined according to the Anticholinergic Cognitive Burden Scale. Standard daily dose (SDD) of PACDs was calculated. A battery of neuropsychological tests was used to assess cognition and the consensus diagnosis was conducted for incident dementia and Alzheimer's disease (AD). Multivariate Cox regression models were used to examine the association between PACD use and the risk of dementia and AD in APOE ε4 carriers and noncarriers. We followed 1406 dementia-free participants for a median of 5.3years and defined 117 incident dementia cases, among which 89 were AD. Only in APOE ε4 carriers was PACD use associated with incident dementia [hazard ratio (HR) 5.71; 95% CI 2.04-15.94] and AD (HR 5.73; 95% CI 1.77-18.54); SDD was positively associated with incident dementia (HR 2.42; 95% CI 1.32-4.44) and AD (HR 2.16; 95% CI 1.06-4.41). Using PACDs requires judicious consideration for the potential risk of dementia and AD in older adults carrying APOE ε4.

Comparison of the telephone-Montreal Cognitive Assessment (T-MoCA) and Telephone Interview for Cognitive Status (TICS) as screening tests for early Alzheimer's disease.

Remote screening for cognitive impairment associated with Alzheimer's disease (AD) has grown in importance with the expected rise in prevalence of AD in an aging population and with new potential treatment options. The Telephone Interview for Cognitive Status (TICS) and new telephone adaptation of the Montreal Cognitive Assessment (T-MoCA) were administered to participants independently classified through in-person clinical evaluation as cognitively normal (CN; n = 167), mild cognitive impairment (MCI; n = 25), or dementia (n = 23). Cerebrospinal fluid AD biomarkers were measured (n = 79). TICS and T-MoCA were highly correlated (r = 0.787; P <0.001): groups differed on both (CN<MCI<dementia; TICS: F [2212] = 156.66; P <0.001; T-MoCA: F [2210] = 143.72; P <0.001), both effectively detected cognitive impairment (receiver operating characteristic area under the curve: TICS = 0.889; T-MoCA = 0.902), and both negatively correlated with a composite AD biomarker (tau/amyloid beta 1-42; TICS: r = -0.372; P = 0.001; T-MoCA: r = -0.480; P <0.001). TICS and T-MoCA are effective for remotely detecting cognitive impairment associated with AD in older adults. Strong correlation between tests provides construct validity for the newer T-MoCA. Construct validity for the telephone adaptation of the Montreal Cognitive Assessment (T-MoCA) was newly established against the Telephone Interview for Cognitive Status (TICS). TICS and T-MoCA effectively detected cognitive impairment with remote administration. Both tests negatively correlated with a composite cerebrospinal fluid Alzheimer's disease (AD) biomarker (tau/amyloid beta 1-42).

Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome

Alzheimer disease (AD) is the main medical problem in adults with Down syndrome (DS). However, the associations of age, intellectual disability (ID), and clinical status with progression and longitudinal cognitive decline have not been established. To examine clinical progression along the AD continuum and its related cognitive decline and to explore the presence of practice effects and floor effects with repeated assessments. This is a single-center cohort study of adults (aged >18 years) with DS with different ID levels and at least 6 months of follow-up between November 2012 and December 2021. The data are from a population-based health plan designed to screen for AD in adults with DS in Catalonia, Spain. Individuals were classified as being asymptomatic, having prodromal AD, or having AD dementia. Neurological and neuropsychological assessments. The main outcome was clinical change along the AD continuum. Cognitive decline was measured by the Cambridge Cognitive Examination for Older Adults With Down Syndrome and the modified Cued Recall Test. A total of 632 adults with DS (mean [SD] age, 42.6 [11.4] years; 292 women [46.2%]) with 2847 evaluations (mean [SD] follow-up, 28.8 [18.7] months) were assessed. At baseline, there were 436 asymptomatic individuals, 69 patients with prodromal AD, and 127 with AD dementia. After 5 years of follow-up, 17.1% (95% CI, 12.5%-21.5%) of asymptomatic individuals progressed to symptomatic AD in an age-dependent manner (0.6% [95% CI, 0%-1.8%] for age <40 years; 21.1% [95% CI, 8.0%-32.5%] for age 40-44 years; 41.4% [95% CI, 23.1%-55.3%] for age 45-49 years; 57.5% [95% CI, 38.2%-70.8%] for age ≥50 years; P < .001), and 94.1% (95% CI, 84.6%-98.0%) of patients with prodromal AD progressed to dementia with no age dependency. Cognitive decline in the older individuals was most common among those who progressed to symptomatic AD and symptomatic individuals themselves. Importantly, individuals with mild and moderate ID had no differences in longitudinal cognitive decline despite having different performance at baseline. This study also found practice and floor effects, which obscured the assessment of longitudinal cognitive decline. This study found an association between the development of symptomatic AD and a high risk of progressive cognitive decline among patients with DS. These results support the need for population health plans to screen for AD-related cognitive decline from the fourth decade of life and provide important longitudinal data to inform clinical trials in adults with DS to prevent AD.

The health status: the ignored risk factor in dementia incidence. NEDICES cohort

The causes of the dementia decrease in affluent countries are not well known but health amelioration could probably play a major role. Nevertheless, although many vascular and systemic disorders in adult life are well-known risk factors (RF) for dementia and Alzheimer disease (AD), health status is rarely considered as a single RF. To analyse whether the health status and the self-perceived health (SPH) could be RF for dementia and AD and to discuss its biological basis. We analysed different objective health measures and SPH as RF for dementia and AD incidence in 4569 participants of the NEDICES cohort by means of Cox-regression models. The mean follow-up period was 3.2 (range: 0.03-6.6) years. Ageing, low education, history of stroke, and "poor" SPH were the main RF for dementia and AD incidence, whereas physical activity was protective. "Poor" SPH had a hazard ratio = 1.66 (95% CI 1.17-2.46; p = 0.012) after controlling for different confounders. According to data from NEDICES cohort, SPH is a better predictor of dementia and AD than other more objective health status proxies. SPH should be considered a holistic and biologically rooted indicator of health status, which can predict future development of dementia and AD in older adults. Our data indicate that it is worthwhile to include the SPH status as a RF in the studies of dementia and AD incidence and to explore the effect of its improvement in the evolution of this incidence.

A modified Cued Recall Test for detecting prodromal AD in adults with Down syndrome.

IntroductionThe development of valid methods to diagnose prodromal Alzheimer's disease (AD) in adults with Down syndrome (DS) is one of the many goals of the Alzheimer's Biomarkers Consortium—Down Syndrome (ABC‐DS).MethodsThe diagnostic utility of a modified Cued Recall Test (mCRT) was evaluated in 332 adults with DS ranging from 25 to 81 years of age. Total recall was selected a priori, as the primary indicator of performance. Multiple regression and receiver‐operating characteristic (ROC) analyses were used to compare diagnostic groups.ResultsPerformance on the mCRT, as indicated by the total recall score, was highly sensitive to differences between diagnostic groups. ROC areas under the curve (AUCs) ranging from 0.843 to 0.955, were observed.,DiscussionThe mCRT has strong empirical support for its use in clinical settings, as a valuable tool in studies targeting biomarkers of AD, and as a potential outcome measure in clinical trials targeting AD in this high‐risk population.

Senescence biomarkers in adults and elderly with Down syndrome

AbstractBackgroundThe Down syndrome (DS) is a genetic disturb caused for the trisomy of chromosome 21. It is the most common cause of intellectual disability, in addition DS accelerates aging and others development and health problems. Some pathological aspects, common to DS with dementia and Alzheimer disease (AD) suggest common pathogenic aspects. This study aims to investigate biomarkers related to cellular aging and their interrelationship with pathological markers of AD in adults and elderly individuals with DS by determining the expression of apoptotic pathway proteins: β‐catenin plays a role int the cell adhesion, cell survival and cell proliferation, in addition it is a key factor in the Wnt pathway. The activation of Wnt/β‐catenin pathway can protect against neurotoxic effects caused by accumulation of β‐amyloid peptide and the phosphorylation of Tau protein, two neuropathological hallmarks in the AD. The Bcl‐2 protein prevents cell death a promoting the cell survival. The tumoral protein P53 functions in the conservation and stability of DNA. It is normally activated in response of cellular stress, acting in the cell cycle, apoptosis, DNA repairing and the cell metabolism.MethodProteins expressions were measured in platelets from non‐medicated older adults with DS (n=37), and healthy adults and older adults (n=28) by western blotting. The samples were analyzed in duplicate and normalization was done using β‐actin as control.Resultβ‐catenin and P53 expressions were higher in DS samples (p=0.001 and p=0.04 respectively). We found a higher expression of Bcl‐2 in healthy control samples (p=0.05).ConclusionWe concluded that the increased expression of β‐catenin and P53, in addition with the decrease levels of Bcl‐2 might indicate a deregulation in the mechanisms responsible for the cell survival process. It is possible to speculate that these changes are related to the increase in cellular stress related to DS.

Genetic overlap between mood disorders and Alzheimer's disease: Could it explain the clinical and epidemiological overlap of these disorders?

Mood disorders such as major depressive (MD) and bipolar (BD), are major risk factors for Alzheimer's disease (AD). History of MD and BD can double the risk of developing AD in older adults, and this risk is even higher when depressive symptoms co-occur with mild cognitive impairment. These evidences suggest that mood disorders and AD may share common biological mechanisms, such as genetic risk factors. However, challenges on conducting multi-phenotype long-follow up studies limit the direct assessment of this hypothesis. Recently, bioinformatics methods using Genome-wide association studies (GWAS) results have been developed and applied to assess the existence of genetic overlap among disorders. Herein, we carried out a multilevel approach to investigate the genetic overlap between mood disorders (MD and BD) and AD, by assessing their genetic correlation, polygenic overlap and shared biological pathways. Summary statistics of three large GWAS for MD, BD and AD were assessed. Genetic overlap and correlation were obtained using LDSC and MiXer. ConjFDR was used to identify pleiotropic loci. Finally, a gene-based approach was applied to obtain a list of overlapping genes and pathways for mood disorders and AD. Pathway enrichment analysis and visualization have been carried out using g:Profiler and Enrichment Map App. Each network (MD&AD, B&AD and MD&BD&AD) was visualized using Cytoscape. Positive genetic correlation among both mood disorders and AD (rG=0.162; p=0.012 for MD&AD; and rG=0.162; p=0.018 for BD&AD) was observed, and further confirmed by all approaches. TMEM106B and THSD7A were identified as pleiotropic candidate genes for MD&AD; and MTSS2, VAC14 and FAF1, for BD&AD. Important biological pathways and functions linking these disorders were highlighted, such as acute inflammatory response, programmed cell death, amyloid-beta response, neuronal death, cell growth, respiratory electron transport chain, lipid metabolism and absorption and membrane trafficking. Our results confirm for the first time the existence of genetic correlation between mood disorders and AD, identify candidate pleiotropic genes and reinforce the existence of a structured biological network among mood disorders and AD. The results obtained herein, once confirmed, may contribute to shed light on future efforts for precision medicine applied to neurodegenerative and mood disorders and their comorbidities.

Association of Apolipoprotein E ɛ4 Allele With Clinical and Multimodal Biomarker Changes of Alzheimer Disease in Adults With Down Syndrome

Alzheimer disease (AD) is the leading cause of death in individuals with Down syndrome (DS). Previous studies have suggested that the APOE ɛ4 allele plays a role in the risk and age at onset of dementia in DS; however, data on in vivo biomarkers remain scarce. To investigate the association of the APOE ɛ4 allele with clinical and multimodal biomarkers of AD in adults with DS. This dual-center cohort study recruited adults with DS in Barcelona, Spain, and in Cambridge, UK, between June 1, 2009, and February 28, 2020. Included individuals had been genotyped for APOE and had at least 1 clinical or AD biomarker measurement; 2 individuals were excluded because of the absence of trisomy 21. Participants were either APOE ɛ4 allele carriers or noncarriers. Participants underwent a neurological and neuropsychological assessment. A subset of participants had biomarker measurements: Aβ1-42, Aβ1-40, phosphorylated tau 181 (pTau181) and neurofilament light chain (NfL) in cerebrospinal fluid (CSF), pTau181, and NfL in plasma; amyloid positron emission tomography (PET); fluorine 18-labeled-fluorodeoxyglucose PET; and/or magnetic resonance imaging. Age at symptom onset was compared between APOE ɛ4 allele carriers and noncarriers, and within-group local regression models were used to compare the association of biomarkers with age. Voxelwise analyses were performed to assess topographical differences in gray matter metabolism and volume. Of the 464 adults with DS included in the study, 97 (20.9%) were APOE ɛ4 allele carriers and 367 (79.1%) were noncarriers. No differences between the 2 groups were found by age (median [interquartile range], 45.9 [36.4-50.2] years vs 43.7 [34.9-50.2] years; P = .56) or sex (51 male carriers [52.6%] vs 199 male noncarriers [54.2%]). APOE ɛ4 allele carriers compared with noncarriers presented with AD symptoms at a younger age (mean [SD] age, 50.7 [4.4] years vs 52.7 [5.8] years; P = .02) and showed earlier cognitive decline. Locally estimated scatterplot smoothing curves further showed between-group differences in biomarker trajectories with age as reflected by nonoverlapping CIs. Specifically, carriers showed lower levels of the CSF Aβ1-42 to Aβ1-40 ratio until age 40 years, earlier increases in amyloid PET and plasma pTau181, and earlier loss of cortical metabolism and hippocampal volume. No differences were found in NfL biomarkers or CSF total tau and pTau181. Voxelwise analyses showed lower metabolism in subcortical and parieto-occipital structures and lower medial temporal volume in APOE ɛ4 allele carriers. In this study, the APOE ɛ4 allele was associated with earlier clinical and biomarker changes of AD in DS. These results provide insights into the mechanisms by which APOE increases the risk of AD, emphasizing the importance of APOE genotype for future clinical trials in DS.