Association Analysis of Apolipoprotein E Genotype and Risk of Depressive Symptoms in Alzheimer’s Disease

Abstract

Objectives: 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 Ε4 in the aetiology of depression in AD. Methods: 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. Results: 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. Conclusions: These results suggest apolipoprotein E genotype creates no additional risk for depressive symptoms in AD.

APOE genotype predicts depression in women with Alzheimer's disease: a retrospective study

“…Indeed, sex effects have not been taken into account in many of the previous studies that have demonstrated negative findings. For example, many studies have not distinguished between men and women across APOE genotypes (Weiner et al, 1998;Cantillon et al, 1997; Harwood, Barker, Ownby, St. GeorgeHyslop, & Duara, 1999;Scarmeas et al, 2002;Craig et al, 2005), have not directly assessed sex differences within their samples (Levy, Cummings, Fairbanks, Sultzer, & Small, 1999;Harwood et al, 1999;Weiner et al, 1999;Scarmeas et al, 2002;Craig et al, 2005), or have not provided sex distributions for their samples (Cantillon et al, 1997). Thus, it is unclear to what extent the lack of measurement for sex differences may have contributed to a lack of association reported in previous studies.…”

“…A recent study suggested that depression and APOE ε4 genotype may be higher in women with AD but not in men (Muller-Thomsen et al, 2002). Despite these findings supporting an association between APOE and depression, several other published studies have not supported the notion that APOE ε4 genotype influences depression in AD (Liu et al, 2002;Scarmeas, et al, 2002;Craig et al, 2005).…”

“…A recent study suggested that depression and APOE ε4 genotype may be higher in women with AD but not in men (Muller-Thomsen et al, 2002). Despite these findings supporting an association between APOE and depression, several other published studies have not supported the notion that APOE ε4 genotype influences depression in AD (Liu et al, 2002;Scarmeas, et al, 2002;Craig et al, 2005).Discrepant findings may be due to a number of factors including small sample sizes, differences in sample compositions (e.g., general "dementia" groups versus strictly diagnosed patients with "probable AD"), and the use of very brief, wide-ranging, or unstructured psychopathology inventories. In addition, others have shown trends toward association between APOE genotype and depression but have rendered conclusions of no relationship.…”

“…Neuropathologically, depressive symptoms appear to be associated with a selective loss of noradrenergic and serotonergic nuclei in the brainstem (Zubenko, 2000) and these losses may be related to genetic risk factors for AD (Craig, Hart, McIlroy, & Passmore, 2005). Although it is now clear that the ε4 allele of the apolipoprotein E gene (APOE-ε4), a plasma protein involved in the transport of cholesterol and lipids throughout the body, is an important risk factor for AD Corder et al, 1993;Farrer et al,1997;Aggarwal et al, 2005), inconsistencies exist across studies investigating whether this susceptibility gene modifies the risk for depression in AD.…”

“…For example, Scarmeas et al (2002) employed a psychiatric inventory that measured only three depression-related symptoms (i.e., depressed mood, change in appetite and sleep problems), two of which are vegetative symptoms and thus problematic for use in older adult samples that frequently have somatic symptoms secondary to physical comorbidity. Similarly, Levy et al (1999) and Craig et al (2005) utilized the Neuropsychiatric Inventory (NPI) which contains few items pertaining to depressive symptoms. Thus, the bulk of published studies reporting a lack of association between APOE ε4 genotype and depression in AD have suffered from small sample sizes, low reported prevalence rates for depression, very brief inventories of depressive symptoms, and/or low diagnostic rigor in the determination of the presence or absence of a DSM-based diagnosis of depression.…”