Association between the
            <i>APOE</i>
            genotype and psychopathologic symptoms in Alzheimer’s disease

Scarmeas, Nikolaos; Brandt, Jason; Albert, Marissa; Devanand, D. P.; Marder, Karen; Bell, Karen L.; Ciappa, Alejandra; Tycko, Ben; Stern, Yaakov

doi:10.1212/wnl.58.8.1182

Cited by 100 publications

(106 citation statements)

References 66 publications

(84 reference statements)

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“…Fifteen studies (including the present one) have examined psychotic symptoms, and six (including the present one) have reported that e4 increased the risk for psychosis (Ramachandran et al, 1996;Ballard et al, 1997;Harwood et al, 1999;Weiner et al, 1999;Scarmeas et al, 2002), whereas nine have found no effect of e4 (Lehtovirta et al, 1996a;Cacabelos et al, 1997;Lopez et al, 1997;Lyketsos et al, 1997;Hirono et al, 1998Hirono et al, , 1999Levy et al, 1999;Gabryelewicz et al, 2002;Sweet et al, 2002). Among the six positive studies only two others (Weiner et al, 1999;Scarmeas et al, 2002) have considered delusions and hallucinations separately. Our exploratory finding that e4 was preferentially associated with delusions was shared by Scarmeas et al (2002) who observed that e4 was associated specifically with an increased risk for delusions in a dose dependent manner, whereas e4 homozygotes actually had a reduced risk for hallucinations.…”

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 68%

“…Among the six positive studies only two others (Weiner et al, 1999;Scarmeas et al, 2002) have considered delusions and hallucinations separately. Our exploratory finding that e4 was preferentially associated with delusions was shared by Scarmeas et al (2002) who observed that e4 was associated specifically with an increased risk for delusions in a dose dependent manner, whereas e4 homozygotes actually had a reduced risk for hallucinations. By contrast, Weiner et al (1999) reported marginal (P ¼ 0.05) positive associations between ApoE e4 and both delusions and hallucinations.…”

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 99%

“…Two recent studies have used Cox proportional hazards analysis to determine whether ApoE e4 influences time to onset of psychosis in patients followed longitudinally, but have reported discrepant results (Scarmeas et al, 2002;Sweet et al, 2002). Sources of variation among these fifteen studies are several, but particularly include differences in psychosis criteria, subject severity, and method of analyzing ApoE e4 status.…”

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 99%

“…Previous studies have used a variety of methods to identify psychotic symptoms in their subjects, including general clinical examination (Lehtovirta et al, 1996a;Lyketsos et al, 1997;Hirono et al, 1999), rating scales (Ballard et al, 1997;Cacabelos et al, 1997;Hirono et al, 1998;Levy et al, 1999;Weiner et al, 1999;Gabryelewicz et al, 2002;Scarmeas et al, 2002), or a combination (Ramachandran et al, 1996;Lopez et al, 1997;Sweet et al, 2002). Those studies that have employed research rating scales have used a wide range of scales (see Table 4), making it difficult to reconcile discrepant reports.…”

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 99%

“…However, the most frequent positive association has been between e4 and psychotic symptoms (delusions or hallucinations). Fourteen previous studies have examined psychotic symptoms, and five have reported that e4 increased the risk for psychosis (Ramachandran et al, 1996;Ballard et al, 1997;Harwood et al, 1999;Weiner et al, 1999;Scarmeas et al, 2002), whereas nine have found no effect of e4 (Lehtovirta et al, 1996a;Cacabelos et al, 1997;Lopez et al, 1997;Lyketsos et al, 1997;Hirono et al, 1998Hirono et al, , 1999Levy et al, 1999;Gabryelewicz et al, 2002;Sweet et al, 2002). Sources of variation among these studies are unclear, but may include differences in patient populations, psychosis criteria, and statistical methods.…”

Section: Introductionmentioning

confidence: 99%

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Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

Zdanys

Kleiman

MacAvoy

et al. 2006

Neuropsychopharmacol

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The apolipoprotein E (ApoE) e4 allele is a well-documented genetic risk factor for sporadic Alzheimer's disease (AD). Its association with psychopathology among AD patients has been the subject of discrepant reports. We aimed to determine whether ApoE e4 + and e4-AD patients exhibit a different risk profile for psychotic symptoms and other behavioral disturbances. The Neuropsychiatric Inventory (NPI) was administered to determine the frequency and severity of psychotic and other behavioral symptoms in a sample of n ¼ 266 AD patients who had been genotyped for ApoE. Multiple logistic regression models were used to calculate the association between the ApoE e4 allele and the presence of psychotic symptoms (delusions or hallucinations). Exploratory analyses were also conducted to determine the impact of disease severity on e4 effects and to examine the association between e4 and other behavioral symptoms. ApoE e4 was significantly associated with psychotic symptoms (odds ratio (OR) ¼ 1.87, 95% CI ¼ 1.07-3.29, P ¼ 0.029), adjusting for age, sex, education, and MMSE score. More stringent definitions of clinically significant psychosis yielded similar results. Exploratory analyses suggested that this effect accrued specifically from patients with severe-stage AD and primarily from an association between e4 and delusions. The e4 allele did not appear to influence the development of most other behavioral symptoms in our sample. In conclusion, AD patients who carry the ApoE e4 allele are at greater risk than noncarriers for developing psychotic symptoms, particularly as the severity of their dementia progresses.

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Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 68%

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 99%

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 99%

Section: Comparison To Other Apoe E4 Ad Psychosis Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

Zdanys

Kleiman

MacAvoy

et al. 2006

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

Seizures in Alzheimer Disease

Scarmeas¹,

Honig²,

Choi³

et al. 2009

Arch Neurol

255

117

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Apolipoprotein E ε4 Allele Genotype and the Effect of Depressive Symptoms on the Risk of Dementia in Men

Irie

Masaki²,

Petrovitch³

et al. 2008

Arch Gen Psychiatry

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Context The apolipoprotein E ε4 (APOE ε4) allele is a genetic risk factor for Alzheimer disease. Recently, depression has also become recognized as a risk factor for dementia. However, the possible effect of the APOE genotype on the association between depression and dementia is unexamined. Objective To examine the independent and combined effects of depression and APOE ε4 on the risk of dementia and its subtypes. Design The Honolulu-Asia Aging Study, a population-based prospective cohort study of Japanese American men. Settings and Participants Depressive symptoms and presence of the APOE ε4 allele were assessed between March 1991 and October 1993 in 1932 cognitively healthy men aged 71 to 90 years. Incident cases of dementia were diagnosed during approximately 6 years of follow-up based on neurologic assessment at 2 repeated examinations (April 1994–April 1996 and October 1997–February 1999). Main Outcome Measures Overall dementia, Alzheimer disease, and vascular dementia. Results The interaction of depression and APOE ε4 was statistically significant in the analytical models. Compared with men with neither APOE ε4 nor depression, the risk of dementia in nondepressed men with APOE ε4 was not significant (hazard ratio, 1.1; 95% confidence interval [CI], 0.6–1.8); however, depressed men without APOE ε4 had a 1.6-fold greater risk (95% CI, 0.8–3.0), whereas depressed men with APOE ε4 had a 7.1-fold greater risk (95% CI, 3.0–16.7) of dementia. For subtypes, we found similar increased risks of Alzheimer disease. Conclusions The APOE ε4 status modifies the association between depressive symptoms and dementia in elderly men. Because individuals with depressive symptoms and the APOE ε4 allele had a markedly increased risk of dementia, one might be especially watchful for early signs of dementia in the older person with depression who is also positive for the APOE ε4 allele. Because this cohort includes only men, further investigation in women is required.

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Association between the APOE genotype and psychopathologic symptoms in Alzheimer’s disease

Cited by 100 publications

References 66 publications

Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

Seizures in Alzheimer Disease

Apolipoprotein E ε4 Allele Genotype and the Effect of Depressive Symptoms on the Risk of Dementia in Men

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