Association analysis of apolipoprotein E genotype and risk of depressive symptoms in Alzheimer's disease.
ABSTRACT Behavioural and psychological symptoms of dementia (BPSD) are potent predictors of carer distress and admission to institutional care. In Alzheimer's disease (AD), depressive symptoms are one of the most common complaints affecting around 50% of all patients. There is speculation these symptoms result from known genetic risk factors for AD, therefore we investigated the role of apolipoprotein E epsilon4 in the aetiology of depression in AD.
In this well-characterised cohort (n = 404) from the relatively genetically homogeneous Northern Ireland population, we tested the hypothesis that genetic variants of apolipoprotein E influence the risk for depressive symptoms in AD patients using the Neuropsychiatric Inventory (NPI-D) to determine the presence of depressive symptoms during the dementing illness.
A total of 55% of patients exhibited a history of depression/dysphoria during the course of the illness as gathered by the NPI-D questionnaire. Forty-six percent were suffering from depression/dysphoria when the analysis was restricted to the month prior to interview. No statistically significant association between genotypes or alleles of apolipoprotein E and depression/dysphoria in AD was observed, nor was any association noted between the presence of severe symptoms and genotypes/alleles of apolipoprotein E.
These results suggest apolipoprotein E genotype creates no additional risk for depressive symptoms in AD.
SourceAvailable from: Yvonne Freund-Levi
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ABSTRACT: Research on the link between APOEε4 and neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) has been inconsistent. Previous work has shown a relationship between serum biomarkers of vascular risk and inflammation and NPS in AD. The current study investigated the impact of APOEε4 status on the relationship between biomarkers of cardiovascular risk, systemic inflammation, and NPS. The sample was drawn from the TARCC Longitudinal Research Cohort; the final sample of 190 consisted of 124 females and 66 males meeting the diagnostic criteria for mild to moderate AD. 115 individuals were APOEε4 carriers and 75 were non-carriers. Serum-based clinical biomarkers of vascular risk and biomarkers of inflammation related to AD were analyzed. NPS data was gathered from caretakers/family members using the Neuropsychiatric Inventory. The significant biomarkers differed for carriers and non-carriers with IL15 being a negative biomarker of total NPS accounting for 12% of the variance for carriers and IL18 and TNFα negative predictors for non-carriers (18% of variance). Patterns related to specific symptoms were similar. Stratification by gender revealed significant biomarkers of total NPS for female carriers were negative IL15 and IL1ra (18% of variance) and for female non-carriers were negative IL18 and positive homocysteine. Total cholesterol was a positive biomarker of total NPS for both male carriers (36% of variance) and non-carriers (negative TNFα and total cholesterol, 32% of variance). These findings suggest that dysregulation of inflammatory activity is related to NPS, that cholesterol is a significant factor in the occurrence of NPS, and that gender and APOE status need to be considered.Journal of Alzheimer's disease: JAD 02/2014; 40(4). DOI:10.3233/JAD-131724 · 3.61 Impact Factor
Article: Neuropsychiatric aspects of dementia[Show abstract] [Hide abstract]
ABSTRACT: Dementia affects approximately 6.5% of people over the age of 65. Whilst cognitive impairment is central to the dementia concept, neuropsychiatric symptoms are invariably present at some stage of the illness. Neuropsychiatric symptoms result in a number of negative outcomes for the individual and their caregivers and are associated with higher rates of institutionalization and mortality. A number of factors have been associated with neuropsychiatric symptoms including neurobiological changes, dementia type, and illness severity and duration. Specific patient, caregiver and environmental factors are also important. Neuropsychiatric symptoms can be broadly divided into four clusters: psychotic symptoms, mood/affective symptoms, apathy, and agitation/aggression. Neuropsychiatric symptoms tend to persist over time although differing symptom profiles exist at various stages of the illness. Assessment should take into account the presenting symptoms together with an appreciation of the myriad of likely underlying causes for the symptoms. A structured assessment/rating tool can be helpful. Management should focus on non-pharmacological measures initially with pharmacological approaches reserved for more troubling symptoms. Pharmacological approaches should target specific symptoms although the evidence-base for pharmacological management is quite modest. Any medication trial should include an adequate appreciation of the risk-benefit profile in individual patients and discussion of these with both the individual and their caregiver.Maturitas 10/2014; 79(2). DOI:10.1016/j.maturitas.2014.04.005 · 2.84 Impact Factor