Dataset Information

Influence of APOE and RNF219 on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer's Disease.

ABSTRACT: The risk for Alzheimer's disease (AD) is associated with the presence of the ?4 allele of Apolipoprotein E (APOE) gene and, recently, with a novel genetic variant of the RNF219 gene. This study aimed at evaluating interactions between APOE-?4 and RNF219/G variants in the modulation of behavioral and cognitive features of two cohorts of patients suffering from mild cognitive impairment (MCI) or AD. We enrolled a total of 173 female MCI or AD patients (83 MCI; 90 AD). Subjects were screened with a comprehensive set of neuropsychological evaluations and genotyped for the APOE and RNF219 polymorphic variants. Analysis of covariance was performed to assess the main and interaction effects of APOE and RNF219 genotypes on the cognitive and behavioral scores. The analysis revealed that the simultaneous presence of APOE-?4 and RNF219/G variants results in significant effects on specific neuropsychiatric scores in MCI and AD patients. In MCI patients, RNF219 and APOE variants worked together to impact the levels of anxiety negatively. Similarly, in AD patients, the RNF219 variants were found to be associated with increased anxiety levels. Our data indicate a novel synergistic activity APOE and RNF219 in the modulation of behavioral traits of female MCI and AD patients.

SUBMITTER: Mosca A

PROVIDER: S-EPMC5932379 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Influence of APOE and RNF219 on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer's Disease.

Mosca Alessandra A Sperduti Samantha S Pop Viorela V Ciavardelli Domenico D Granzotto Alberto A Punzi Miriam M Stuppia Liborio L Gatta Valentina V Assogna Francesca F Banaj Nerisa N Piras Fabrizio F Piras Federica F Caltagirone Carlo C Spalletta Gianfranco G Sensi Stefano L SL

Frontiers in aging neuroscience 20180413

The risk for Alzheimer's disease (AD) is associated with the presence of the 𝜀4 allele of Apolipoprotein E (APOE) gene and, recently, with a novel genetic variant of the RNF219 gene. This study aimed at evaluating interactions between APOE-𝜀4 and RNF219/G variants in the modulation of behavioral and cognitive features of two cohorts of patients suffering from mild cognitive impairment (MCI) or AD. We enrolled a total of 173 female MCI or AD patients (83 MCI; 90 AD). ...[more]

PMID: 29755337

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Project description:Mild behavioral impairment (MBI) is a high-risk state for incident dementia and comprises five core domains including affective dysregulation, impulse dyscontrol, social inappropriateness, psychotic symptoms, and apathy. Apathy is among the most common neuropsychiatric symptoms (NPS) in dementia but can also develop in persons with normal cognition (NC) or mild cognitive impairment (MCI). The later-life emergence and persistence of apathy as part of the MBI syndrome may be a driving factor for dementia risk. Therefore, we investigated MBI-apathy-associated progression to dementia, and effect modification by sex, race, cognitive diagnosis, and apolipoprotein E (APOE) genotype. Dementia-free National Alzheimer's Coordinating Center participants were stratified by persistent apathy status, based on Neuropsychiatric Inventory (NPI)-Questionnaire scores at two consecutive visits. Hazard ratios (HRs) for incident dementia for MBI-apathy and NPI-apathy relative to no NPS, and MBI-apathy relative to no apathy, were determined using Cox proportional hazards regressions, adjusted for baseline age, sex, years of education, race, cognitive diagnosis, and APOE genotype. Interactions with relevant model covariates were explored. Of the 3932 participants (3247 with NC), 354 had MBI-apathy. Of all analytic groups, MBI-apathy had the greatest dementia incidence (HR = 2.69, 95% confidence interval [CI]: 2.15-3.36, P < 0.001). Interaction effects were observed between cognitive diagnosis and APOE genotype with the NPS group. The contribution of apathy to dementia risk was greater in NC (HR = 5.91, 95% CI: 3.91-8.93) than in MCI (HR = 2.16, 95% CI: 1.69-2.77, interaction P < 0.001) and in all APOE genotypes, was greatest in APOE ɛ3 (HR = 4.25, 95% CI: 3.1-5.82, interaction P < 0.001). Individuals with MBI-apathy have a markedly elevated risk for future dementia, especially when symptoms emerge in those with NC. Both cognitive status and APOE genotype are important moderators in the relationship between MBI-apathy and incident dementia. MBI-apathy may represent a group in whom apathy is a preclinical or prodromal manifestation of dementia and identify a precision medicine target for preventative interventions.

Dataset Information

Influence of APOE and RNF219 on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer's Disease.

Publications

Influence of <i>APOE</i> and <i>RNF219</i> on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer's Disease.

Similar Datasets

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