Association Analysis of Apolipoprotein E Genotype and Risk of Depressive Symptoms in Alzheimer’s Disease
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.
Available from: Francesco Panza
- "Longitudinal 87 AD patients MMSE, CUSPAD, BDRS, and SCID-DSM-III-R APOE 4 alleles associated with risk for incident delusions. APOE 4/4 predicted protective effect against hallucinations Gabryelewicz et al. (2002) Cross-sectional 139 AD patients MMSE, GDS, and BEHAVE-AD The APOE e4 allele had no effect on the behavioural changes in AD Craig et al. (2005) Cross-sectional 404 AD patients MMSE and NPI with caregiver distress "
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ABSTRACT: Neuropsychiatric symptoms (NPS) in dementia, previously denominated as behavioural and psychological symptoms of dementia, are often more distressing, impairing, and costly than cognitive symptoms, representing a major health burden for older adults. These symptoms are common features of Alzheimer's disease (AD), and are one of the major risk factors for institutionalization. There is a high prevalence of neuropsychiatric disturbances in patients with AD, including depression, anxiety, apathy, psychosis, aggression, and agitation. At present, the role of the apolipoprotein E (APOE) genotypes in the development of NPS or neuropsychiatric syndromes/endophenotypes in AD patients is unclear. In this article, we summarized the findings of the studies of NPS and neuropsychiatric syndromes in AD in relation to APOE genotypes, with special attention to the possible underlying mechanisms. While some studies failed to find a significant association between the APOE polymorphism and NPS in late-onset AD, other studies reported a significant association between the APOE ɛ4 allele and an increase in agitation/aggression, hallucinations, delusions, and late-life depression or anxiety. However, current cumulative evidence coming from the few existing longitudinal studies shows no association of APOE genotypes with NPS as a whole in AD. Some negative studies that focused on the distribution of APOE genotypes between AD patients with or without NPS further emphasized the importance of sub-grouping NPS in distinct neuropsychiatric syndromes. Explanations for the variable findings in the existing studies included differences in patient populations, differences in the assessment of neuropsychiatric symptomatology, possible lack of statistical power to detect associations in the negative studies, and small sample sizes generating false positives that cannot be consistently replicated. Finally, many reviewed studies were cross-sectional, whereas it would be of paramount importance to evaluate the risk for incident NPS in relation to the APOE genotype in prospectively followed cohorts of AD patients. In fact, identifying predisposing genetic risk factors may allow us to understand the pathophysiological features of neuropsychiatric syndromes or symptoms in AD, so optimizing possible therapeutic options.
Available from: Patrizia Mecocci
- "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 [25, 58, 66–69, 71], also when specific AD endophenotypes were considered [28, 29] (Table 1). Other reports suggested that in AD the APOE ε4 allele may be protective against depression  or that APOE ε2-carriers may be at higher risk of depressive symptoms [53–55]. "
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ABSTRACT: Neuropsychiatric symptoms, previously denominated as behavioural and psychological symptoms of dementia, are common features of Alzheimer's disease (AD) and are one of the major risk factors for institutionalization. At present, the role of the apolipoprotein E (APOE) gene in the development of neuropsychiatric symptoms in AD patients is unclear. In this paper, we summarized the findings of the studies of neuropsychiatric symptoms and neuropsychiatric syndromes/endophenotypes in AD in relation to APOE genotypes, with special attention to the possible underlying mechanisms. While some studies failed to find a significant association between APOE and neuropsychiatric symptoms in late-onset AD, other studies reported a significant association between the APOE ε4 allele and an increase in agitation/aggression, hallucinations, delusions, and late-life depression or anxiety. Furthermore, some negative studies that focused on the distribution of APOE genotypes between AD patients with or without neuropsychiatric symptoms further emphasized the importance of subgrouping neuropsychiatric symptoms in distinct neuropsychiatric syndromes. Explanations for the variable findings in the existing studies included differences in patient populations, differences in the assessment of neuropsychiatric symptomatology, and possible lack of statistical power to detect associations in the negative studies.
Available from: Natalie L Marchant
- "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. George- Hyslop, & 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. "
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ABSTRACT: The association between the APOE epsilon4 allele and depression was investigated in a retrospective study of 323 AD patients.
Patients were divided into demographically comparable groups based on the presence or absence of depression.
Results showed that the frequency of APOE epsilon4 allele was significantly higher in the depressed vs non-depressed AD patients (72% and 58%, respectively), and an interaction revealed that women possessing the APOE epsilon4 allele were almost four times more likely to be depressed than those without the epsilon4 allele.
Results are consistent with recent suggestions that the APOE epsilon4 genotype may be over-represented among depressed women with AD and highlight the need for additional research investigating the links between APOE genotype, mood, and gender.
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