Association of the APOE ε4 allele with clinical subtypes of late life depression

Zubenko, George S.; Henderson, Richelle; Stiffler, J. Scott; Stabler, Stacy M.; Rosen, Jules; Kaplan, Barry B.

doi:10.1016/s0006-3223(96)00046-7

Cited by 77 publications

(68 citation statements)

References 49 publications

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“…However, among ApoE ε4 noncarriers, the MCI subjects had lower premorbid and current neuroticism and higher premorbid and current extraversion scores compared to the control subjects, whereas the MCI patients and the control subjects who were ApoE ε4 carriers obtained similar scores. To our knowledge, this is the first study reporting on ApoE status in relation to personality traits in MCI, although there are a number of investigations into BPS as state markers in AD showing contradictory findings as to their association with the ApoE ε4 genotype [18,19,20,21,22,23,24,25]. Our results may be a chance finding given the preliminary nature of this study.…”

Section: Discussionmentioning

confidence: 58%

“…Apolipoprotein E ε4 allele (ApoE ε4) and tau protein were associated with MCI conversion to AD [15,16,17]. Moreover, BPS as state markers in AD have been found to be associated with ApoE ε4 and less with ApoE ε3 genotypes [18,19,20,21,22,23], although some studies contradict such findings [24,25]. We have found no studies reporting on ApoE status in relation to BPS and personality traits in MCI.…”

Section: Introductionmentioning

confidence: 99%

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The Evolution of Personality in Patients with Mild Cognitive Impairment

Donati

Studer

Petrillo

et al. 2013

Dement Geriatr Cogn Disord

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Aims: To describe personality traits and their changes in mild cognitive impairment (MCI) and control subjects. Methods: Sixty-three MCI and 90 control subjects were asked to describe their current personality traits by the Structured Interview for the Five-Factor Model (SIFFM). For each subject, a close relative retrospectively assessed these descriptions both as to the previous and current personality traits, using the Revised NEO Personality Inventory, Form R (NEO-PI-R). Results: Self-assessed MCI subjects reported significantly lower scores in the openness dimension than control subjects [F(1, 150) = 9.84, p = 0.002, η_p² = 0.06]. In current observer ratings, MCI subjects had higher scores on neuroticism [F(1, 137) = 7.55, p = 0.007, η_p² = 0.05] and lower ones on extraversion [F(1, 137) = 6.40, p = 0.013, η_p² = 0.04], openness [F(1, 137) = 9.93, p = 0.002, η_p² = 0.07], agreeableness [F(1, 137) = 10.18, p = 0.002, η_p² = 0.07] and conscientiousness [F(1, 137) = 25.96, p < 0.001, η_p² = 0.16]. Previous personality traits discriminated the groups as previous openness [odds ratio (OR) = 0.97, 95% confidence interval (CI) = 0.95-0.99, p = 0.014] and conscientiousness (OR = 0.96, 95% CI 0.94-0.98, p = 0.001) were negatively related to MCI group membership. In MCI subjects, conscientiousness [F(1, 137) = 19.20, p < 0.001, η_p² = 0.12] and extraversion [F(1, 137) = 22.27, p < 0.001, η_p² = 0.14] decreased between previous and current evaluations and neuroticism increased [F(1, 137) = 22.23, p < 0.001, η_p² = 0.14], whereas no significant change was found in control subjects. Conclusions: MCI subjects undergo significant personality changes. Thus, personality assessment may aid the early detection of dementia.

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Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

The Evolution of Personality in Patients with Mild Cognitive Impairment

Donati

Studer

Petrillo

et al. 2013

Dement Geriatr Cogn Disord

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“…However, recent evidence has been accumulating to suggest that APOE, a low density protein, may be linked to vascular risk factors in late life and, in turn, may be associated with depression (Lavretsky et al, 2000). Indeed, apolipoprotein E is known to play a role in lipid metabolism, cholesterol transport, and neuronal repair (Zubenko et al, 1996), and it has been posited that the ε4 allele may be a predisposing genetic marker for ischemic cerebrovascular disease (Hoffman, Ott, & Breteler et al, 1997;McCarron, Delong, & Alberts, 1999) given its association with hyperlipidemia (Sawada et al, 2000), atherosclerosis (Davignon, Cohn, Mabile, & Bernier, 1999), myocardial infarction (Brscic, 2000), and subcortical white matter lesion pathology (de Leeuw et al, 2004). Moreover, vascular risk factors have been closely linked with depression in late-life and it has been suggested that they may predispose or give rise to depressive symptoms ("vascular depression hypothesis;" Alexopoulos et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

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

Delano‐Wood

Houston

Emond

et al. 2007

Int J Geriat Psychiatry

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The association between the epsilon-4 type allele of apolipoprotein E (APOE ε4) and depression was investigated in 323 AD patients. Patients were divided into two groups based on the presence (n=61) or absence (n=262) of depression as assessed by the DSM-based Diagnostic Interview Schedule. Both subgroups were demographically comparable with regard to age, education, gender, and severity of cognitive impairment. Analysis of the frequency of APOE ε4 alleles between the groups revealed a significantly higher prevalence rate of the APOE ε4 genotype in the depressed group (72% of depressed AD patients carried at least one copy of the ε4 allele) compared to the non-depressed AD patients (58%). This effect was primarily accounted for by women. Specifically, an interaction was revealed wherein women who possessed the APOE ε4 allele were almost 4 times more likely to be depressed in comparison to those who did not carry the allele, and APOE ε4 status did not predict depression among men in our sample. These results are consistent with recent suggestions that the APOE ε4 genotype may be over-represented among women with AD and depression and highlight a need for additional research investigating the links between APOE genotype, mood, and gender.Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive neuropsychological, functional, and behavioral decline. Currently, there are 4.5 million people with AD in the United States and the prevalence is expected to increase to 11 -16 million by 2050 (Alzheimer's Association, 2004. Psychiatric disturbance is frequently seen in AD and, although prevalence rates vary considerably across studies (e.g., 1 -90%), average rates of coexisting AD and depression appear to hover around 20 to 40% (Wragg & Jeste, 1989;Cummings, Ross, Absher, Gornbein & Hadjiaghai, 1995;Tractenberg, Weiner, Patterson, Teri, & Thal, 2003;Green et al., 2003). Lyketsos and Olin (2002) reported that behavioral disturbances among AD patients are 3 to 4 times higher than that seen in normal aging.Adverse consequences of depression in patients with AD are numerous, including greater impairment in activities of daily living (Lyketsos et al., 1997b), poorer quality of life (GonzalesSalvador et al., 2000), earlier institutionalization (Magni, Bionetti, Bianchetti, & Trabucchi, 1996), greater caregiver depression and level of burden (Gonzales-Salvador et al., 1999) (Stern et al., 1997), and higher mortality rates (Ganguli, Hodge, & Mulsant, 2002;Hoch et al., 1993). In addition, neuropsychiatric symptoms significantly increase direct annual costs of care among AD patients, even after adjusting for the severity of cognitive impairment and other medical comorbidities (Murman et al, 2002).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 ...

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“…Does ApoE e2 have a protective role, with carriers of this allele having a later age of onset? Studies (Forsell et al, 1997;Holmes et al, 1998;Zubenko et al, 1996) comparing ApoE allele frequencies in depressed aged subjects across differing ages of onset with frequencies in age-matched controls have found little evidence that carriers of the ApoE e4 allele have an increased risk of developing depressive illness or have an earlier age of onset, but have found some, albeit modest, evidence that carriers of the ApoE e2 allele are offered some protection from the disease with a delayed onset. Studies of ApoE allele frequencies in subjects with late-onset (over the age of 45 years) depressive illness have been inconclusive; one early study (Krishnan et al, 1996) showed evidence for an increased frequency of the ApoE e4 allele in the late-onset group compared with both the early-onset group and controls, but another study (Heidrich et al, 1997) found no such evidence.…”

Section: Guest Editorials Apolipoprotein E and Functional Illness In mentioning

confidence: 99%

Apolipoprotein E and Functional Illness in the Elderly

Holmes

1998

Int. Psychogeriatr.

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Following on from the hypothesis of a role for the ApoE ε4 and ε2 alleles as risk and protective factors, respectively, for late-onset Alzheimer's disease (AD) came inevitable questions regarding other psychiatric conditions of late onset including depressive illness and schizophrenia. Is ApoE ε4 a risk factor in these diseases and do carriers have an earlier age of onset? Does ApoE ε2 have a protective role, with carriers of this allele having a later age of onset?

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Association of the APOE ε4 allele with clinical subtypes of late life depression

Cited by 77 publications

References 49 publications

The Evolution of Personality in Patients with Mild Cognitive Impairment

The Evolution of Personality in Patients with Mild Cognitive Impairment

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

Apolipoprotein E and Functional Illness in the Elderly

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