Association Between the APOE ɛ2/ɛ4 Genotype and Alzheimer’s Disease and Mild Cognitive Impairment Among African Americans

2021 ◽  
pp. 1-6
Author(s):  
Dianxu Ren ◽  
Oscar L. Lopez ◽  
Jennifer H. Lingler ◽  
Yvette Conley
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
African Americans ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Increased Risk ◽  
Similar Risk

We examined the association between APOE ɛ2/ɛ4 with incident Alzheimer’s disease (AD) and mild cognitive impairment (MCI) among African Americans using the national dataset from the National Alzheimer’s Coordinating Center (NACC) from 2005 to September 2019. Compared to ɛ3/ɛ3 carriers, ɛ2/ɛ4 carriers exhibited a similar risk of incident AD (adjusted hazard ratio [aHR] = 0.85, 95% CI [0.39, 1.84]) among the AD cohort and similar risk of incident MCI (aHR = 0.88, 95% CI [0.51, 1.50]) among the MCI cohort. Our findings suggest that, unlike the increased risk of AD and MCI in non-Latino whites, APOE ɛ2/ɛ4 genotype is not associated with the incidence of AD and MCI among African Americans.

scholarly journals Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?

2016 ◽  
Vol 10 (3) ◽  
pp. 170-177 ◽  
Author(s):  
Adalberto Studart Neto ◽  
Ricardo Nitrini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Clinical Manifestation ◽  
Neurodegenerative Disorder ◽  
Subjective Cognitive Decline ◽  
Subjective Memory ◽  
Increased Risk

ABSTRACT Background: Mild cognitive impairment is considered as the first clinical manifestation of Alzheimer's disease (AD), when the individual exhibits below performance on standardized neuropsychological tests. However, some subjects before having a lower performance on cognitive assessments already have a subjective memory complaint. Objective: A review about subjective cognitive decline, the association with AD biomarkers and risk of conversion to dementia. Methods: We performed a comprehensive non-systematic review on PubMed. The keywords used in the search were terms related to subjective cognitive decline. Results: Subjective cognitive decline is characterized by self-experience of deterioration in cognitive performance not detected objectively through formal neuropsychological testing. However, various terms and definitions have been used in the literature and the lack of a widely accepted concept hampers comparison of studies. Epidemiological data have shown that individuals with subjective cognitive decline are at increased risk of progression to AD dementia. In addition, there is evidence that this group has a higher prevalence of positive biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is not the only cause of subjective cognitive decline and various other conditions can be associated with subjective memory complaints, such as psychiatric disorders or normal aging. The features suggestive of a neurodegenerative disorder are: onset of decline within the last five years, age at onset above 60 years, associated concerns about decline and confirmation by an informant. Conclusion: These findings support the idea that subjective cognitive complaints may be an early clinical marker that precedes mild cognitive impairment due to Alzheimer's disease.

Multicenter Study on Sleep and Circadian Alterations as Objective Markers of Mild Cognitive Impairment and Alzheimer’s Disease Reveals Sex Differences

2020 ◽  
Vol 78 (4) ◽  
pp. 1707-1719
Author(s):  
Biancamaria Guarnieri ◽  
Michelangelo Maestri ◽  
Federico Cucchiara ◽  
Annalisa Lo Gerfo ◽  
Alessandro Schirru ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Differences ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Health Status ◽  
Type I ◽  
Activity Trackers ◽  
Increased Risk ◽  
Wearable Activity Trackers

Background: Circadian and sleep disturbances are associated with increased risk of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Wearable activity trackers could provide a new approach in diagnosis and prevention. Objective: To evaluate sleep and circadian rhythm parameters, through wearable activity trackers, in MCI and AD patients as compared to controls, focusing on sex dissimilarities. Methods: Based on minute level data from consumer wearable devices, we analyzed actigraphic sleep parameters by applying an electromedical type I registered algorithm, and the corresponding circadian variables in 158 subjects: 86 females and 72 males (42 AD, 28 MCI, and 88 controls). Moreover, we used a confusion-matrix chart method to assess accuracy, precision, sensitivity, and specificity of two decision-tree models based on actigraphic data in predicting disease or health status. Results: Wake after sleep onset (WASO) was higher (p < 0.001) and sleep efficiency (SE) lower (p = 0.003) in MCI, and Sleep Regularity Index (SRI) was lower in AD patients compared to controls (p = 0.004). SE was lower in male AD compared to female AD (p = 0.038) and SRI lower in male AD compared to male controls (p = 0.008), male MCI (p = 0.047), but also female AD subjects (p = 0.046). Mesor was significantly lower in males in the overall population. Age reduced the dissimilarities for WASO and SE but demonstrated sex differences for amplitude (p = 0.009) in the overall population, controls (p = 0.005), and AD subjects (p = 0.034). The confusion-matrices showed good predictive power of actigraphic data. Conclusion: Actigraphic data could help identify disease or health status. Sex (possibly gender) differences could impact on neurodegeneration and disease trajectory with potential clinical applications.

Perceived Stress is Associated with Alzheimer’s Disease Cerebrospinal Fluid Biomarkers in African Americans with Mild Cognitive Impairment

2020 ◽  
Vol 77 (2) ◽  
pp. 843-853
Author(s):  
Antoine R. Trammell ◽  
Darius J. McDaniel ◽  
Malik Obideen ◽  
Maureen Okafor ◽  
Tiffany L. Thomas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
African Americans ◽  
Racial Differences ◽  
Perceived Stress ◽  
Cross Sectional Study ◽  
Cross Sectional

Background: African Americans (AA) have a higher Alzheimer’s disease (AD) prevalence and report more perceived stress than White Americans. The biological basis of the stress-AD link is unclear. This study investigates the connection between stress and AD biomarkers in a biracial cohort. Objective: Establish biomarker evidence for the observed association between stress and AD, especially in AA. Methods: A cross-sectional study (n = 364, 41.8% AA) administering cognitive tests and the perceived stress scale (PSS) questionnaire. A subset (n = 309) provided cerebrospinal fluid for measurement of Aβ42, Tau, Ptau, Tau/Aβ42 (TAR), and Ptau/Aβ42 (PTAR). Multivariate linear regression, including factors that confound racial differences in AD, was performed. Results: Higher PSS scores were associated with higher Ptau (β= 0.43, p = 0.01) and PTAR (β= 0.005, p = 0.03) in AA with impaired cognition (mild cognitive impairment). Conclusion: Higher PSS scores were associated with Tau-related AD biomarker indices in AA/MCI, suggesting a potential biological connection for stress with AD and its racial disparity.

scholarly journals PVRL2 rs6859 Modifies the Effect of Triglyceride on Progression of Mild Cognitive Impairment: The Shanghai Aging Study

2020 ◽  
Author(s):  
Ruru Wang ◽  
Ding Ding ◽  
Abuduaili Atibaike ◽  
Jianxiong Xi ◽  
Qianhua Zhao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cox Model ◽  
Association Studies ◽  
Interactive Effect ◽  
Genome Wide Association Studies ◽  
Increased Risk ◽  
Aging Study

Abstract Background Mild cognitive impairment (MCI) is an intermediate stage between normal cognition and Alzheimer’s disease (AD). Genome-wide association studies (GWAS) have identified many AD-risk variants and indicated the important role of lipid metabolism pathway in AD progression. This study aimed to investigate the effects of triglyceride (TG) and genetic risk factors on progression from MCI to AD (MCI-AD progression).Methods The current study sample comprised of 305 MCI subjects aged 50 and over who were prospectively followed up for average 4.5 years in a sub-cohort of the Shanghai Aging Study. A consensus diagnosis of incident AD was conducted according to Diagnostic and Statistical Manual of Mental Disorders-IV and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association criteria. Fasting blood samples were obtained at baseline for analyzing serum TG. Single nucleotide polymorphisms (SNPs) genotyping was performed using a MassARRAY system. The effect of TG, genetic variants and their interaction on MCI-AD progression were analyzed using Cox proportional hazards regression model.Results During a mean (±SD) follow-up period of 4.5±1.3 y, 58 subjects developed incident AD. The SNP, rs6859 in the Poliovirus Receptor–Related 2 (PVRL2) gene, was significantly associated with incident AD (false discovery rate (FDR)-adjusted P = 0.018). In multivariate cox model, the PVRL2 rs6859 AG, AA and AG+AA genotypes were associated with significantly increased incident AD, compared with the GG genotype (hazard ratio [HR] = 2.29, P = 0.029, and HR = 2.92, P = 0.013, and HR = 2.47, P =0.012, respectively). In PVRL2 rs6859 AG/AA carriers, higher ln TG was significantly associated with increased risk of incident AD (adjusted HR =2.64, P = 0.034). Ln TG and PVRL2 rs6859 had interactive effect on the MCI-AD progression (P Ln TG × rs6859 = 0.001). Conclusion The present study indicated that PVRL2 rs6859 modified the effect of TG on MCI-AD progression. Precision prevention in MCI population based on genetic information should be considered to avoid progression to AD.

Association Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Hongliang Liu ◽  
Michael Lutz ◽  
Sheng Luo ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Clinical Changes

Background: Mild cognitive impairment (MCI) is a heterogeneous condition and MCI patients are at increased risk of progression to dementia due to Alzheimer’s disease (AD). Objective: In this study, we aim to evaluate the associations between polygenic risk scores (PRSs) and 1) time to AD progression from MCI, 2) changes in longitudinal cognitive impairment, and 3) biomarkers from cerebrospinal fluid and imaging. Methods: We constructed PRS by using 40 independent non-APOE SNPs from well-replicated AD GWASs and tested its association with the progression time from MCI to AD by using 767 MCI patients from the ADNI study and 1373 patients from the NACC study. PRSs calculated with other methods were also computed. Results: We found that the PRS constructed with SNPs that reached genome-wide significance predicted the progression from MCI to AD (beta = 0.182, se = 0.061, p = 0.003) after adjusting for the demographic and clinical variables. This association was replicated in the NACC dataset (beta = 0.094, se = 0.037, p = 0.009). Further analyses revealed that PRS was associated with the increased ADAS-Cog11/ADAS-Cog13/ADASQ4 scores, tau/ptau levels, and cortical amyloid burdens (PIB and AV45), but decreased hippocampus and entorhinal cortex volumes (p <  0.05). Mediation analysis showed that the effect of PRS on the increased risk of AD may be mediated by Aβ 42 (beta = 0.056, SE = 0.026, p = 0.036). Conclusion: Our findings suggest that PRS can be useful for the prediction of time to AD and other clinical changes after the diagnosis of MCI.

Diabetes is associated with cognitive impairment no dementia in the aging, demographics, and memory study (ADAMS)

2012 ◽  
Vol 25 (1) ◽  
pp. 167-168 ◽  
Author(s):  
Christine E. Gould ◽  
Sherry A. Beaudreau ◽  
Huma Salman
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Increased Risk ◽  
Cognitive Impairment No Dementia

Individuals with diabetes mellitus have a 1.39 times increased risk of Alzheimer's disease, a 2.38 times increased risk of vascular dementia, and a faster rate of cognitive decline compared to individuals without diabetes (Lu et al., 2009). In a study, over a 9-year follow-up diabetes was associated with accelerated progression from mild cognitive impairment (MCI) to dementia, but was not associated with progression from no impairment to MCI (Xu et al., 2010). Many previous studies on cognitive impairment and diabetes are limited by the use of cognitive screens to diagnose and assess cognitive impairment. A few studies diagnosing cognitive impairment with comprehensive neuropsychological batteries provide mixed results. For instance, Luchinger et al. (2007) found that diabetes was correlated with the presence of MCI, whereas diabetes was not associated with the presence of dementia versus no dementia in the Aging, Demographics, and Memory Study ADAMS; (Llewellyn et al., 2010).

scholarly journals MACHINE LEARNING MODEL BASED ON A PANEL OF PLASMA PROTEINS PREDICTS PROGRESSION FROM MILD COGNITIVE IMPAIRMENT TO DEMENTIA DUE TO ALZHEIMER’S DISEASE WITHIN FOUR YEARS

2021 ◽  
Author(s):  
Daniella Araujo ◽  
Paulo Caramelli ◽  
Nivio Ziviani ◽  
Karina Gomes ◽  
Adriano Veloso ◽  
...  
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Plasma Proteins ◽  
Risk Model ◽  
Disease Stage ◽  
Lifestyle Interventions ◽  
Increased Risk

Background: Alzheimer’s disease (AD) is a pathological process that begins many years prior to the emergence of symptoms. Thus, an effective risk model for AD should aim at detecting at-risk individuals in the prodromal stage, when treatments and lifestyle interventions are more likely to be successful, and should be minimally invasive and inexpensive to allow widespread applicability. Objectives: To develop a machine learning based blood panel in individuals with mild cognitive impairment (MCI) to predict increased risk for progression to AD dementia. Methods: We created over one billion models to predict the probability of conversion from MCI to dementia due to AD, and chose the best performing one. We used the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data of 380 MCI individuals in the baseline visit, from which 177 converted to AD dementia. Results: The best performing model uses 12 plasma proteins (out of 146 possibilities), giving an average AUC of 0.91, accuracy of 0.92, sensitivity of 0.97 and specificity of 0.85. Conclusions: We were able to predict AD dementia conversion within four years in MCI individuals, a disease stage in which treatments and lifestyle interventions are more likely to be successful. Further studies in independent cohorts are needed to validate this panel.

Incidence of and Risk Factors for Alzheimer's Disease and Mild Cognitive Impairment in Korean Elderly

2014 ◽  
Vol 39 (1-2) ◽  
pp. 105-115 ◽  
Author(s):  
Jong Bin Bae ◽  
You Joung Kim ◽  
Ji Won Han ◽  
Tae Hui Kim ◽  
Joon Hyuk Park ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Formal Education ◽  
Nationwide Survey ◽  
Incidence Rates ◽  
Increased Risk ◽  
Korean Elderly

Background/Aims: Knowledge of incidence rates and risk factors is essential for the development of strategies to treat patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Methods: A subpopulation of the Nationwide Survey on Dementia Epidemiology (460 Korean subjects aged ≥65 years from 2 rural and 2 urban districts) was followed up for 3.5 years. The age-specific incidence was estimated and risk factors were identified. Results: The age-standardized incidence of AD and MCI was 7.9 and 28.1 cases per 1,000 person-years, respectively. MCI was associated with a 6-fold increased risk of AD. Depression was a risk factor for AD with MCI. Age, lack of formal education, illiteracy, rural residence, and marital status were associated with the risk of AD. Conclusion: Strategies to control modifiable risk factors should be implemented to decrease the incidence of AD. © 2014 S. Karger AG, Basel

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