Absence of an Apolipoprotein E ϵ4 Allele Is Associated With Increased Parietal Regional Cerebral Blood Flow Asymmetry in Alzheimer Disease

Dyck, Christopher H. van; Gelernter, Joel; MacAvoy, Martha G.; Avery, Robert A.; Criden, Marc; Okereke, Olivia I.; Varma, Pradeep; Seibyl, John; Hoffer, Paul B.

doi:10.1001/archneur.55.11.1460

Cited by 30 publications

(21 citation statements)

References 34 publications

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“…Family history of AD has been shown to be a risk factor for AD beyond the eff ect of 4 alone [55] , which is one refl ection of the existence of additional genetic or environmental risk factors for AD. Samples of 4-negative AD patients are likely enriched for these factors [61] , which may in turn be associated with a form of AD conferring a later age of onset but equal or increased rates of clinical progression. Th us, the growing body of research examining phenotypic associations of ApoE 4 in AD samples is almost certainly confounded by an effective disequilibrium with other factors.…”

Section: Interpretation Of a Negative Eff Ect Of Apoe 4 On Ad Progressupporting

confidence: 65%

Apolipoprotein E ε4 Allele Is Unrelated to Cognitive or Functional Decline in Alzheimer’s Disease: Retrospective and Prospective Analysis

Kleiman

Zdanys

Black

et al. 2006

Dement Geriatr Cogn Disord

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Objective: The apolipoprotein E (ApoE) Ε4 allele is a well-documented genetic risk factor for Alzheimer’s disease (AD). Its role, if any, in the progression of cognitive and functional impairment in AD has been the subject of discrepant reports in the literature. This study aimed to determine whether ApoE Ε4 dose is related to the progression of cognitive and functional decline in AD patients by combined retrospective and prospective analyses. Methods: A sample of 366 AD patients was genotyped for ApoE. Subjects received tests of cognition (Mini-Mental State Examination, MMSE; Alzheimer’s Disease Assessment Scale-Cognitive subscale, ADAS-Cog) and daily function (Instrumental Activities of Daily Living, IADL; Alzheimer’s Disease Cooperative Study-Activities of Daily Living, ADCS-ADL) at baseline and at multiple subsequent time points during their participation in a variety of research protocols. In retrospective analyses, scores on baseline cognitive and functional measures were compared cross-sectionally among genotype groups, controlling for duration of symptoms. In prospective analyses, longitudinal rates of change for each measure were computed by linear regression and compared across genotype groups. Results: No association was observed between ApoE Ε4 dose and any of the retrospective or prospective measures of cognitive or functional decline in this AD patient sample. Conclusions: Although ApoE Ε4 increases the risk for AD and decreases the age of disease onset in population studies, it did not significantly influence the rate of disease progression in cognitive or functional domains in our sample.

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Section: Interpretation Of a Negative Eff Ect Of Apoe 4 On Ad Progressupporting

confidence: 65%

Apolipoprotein E ε4 Allele Is Unrelated to Cognitive or Functional Decline in Alzheimer’s Disease: Retrospective and Prospective Analysis

Kleiman

Zdanys

Black

et al. 2006

Dement Geriatr Cogn Disord

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“…[17][18][19] Furthermore, Hirono et al 20 provided evidence that the hypometabolism within the parietotemporal and medial temporal areas varies between early onset e3/e3 and e4/e4 carriers, but that these differences are lost for late onset patients. Together with previous research, the present results suggest that at the onset of AD cognitive symptoms, possible METglc differences between the ApoE genotype groups are no longer detectable within these mainly hypometabolic areas in AD.…”

Section: Discussionmentioning

confidence: 99%

Brain metabolic decreases related to the dose of the ApoE e4 allele in Alzheimer's disease

Mosconi

Nacmias²,

Sorbi³

et al. 2004

Journal of Neurology, Neurosurgery & Psychiatry

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Objectives: Declines in brain glucose metabolism have been described early in Alzheimer's disease (AD), and there is evidence that a genetic predisposition to AD contributes to accelerate this process. The epsilon4 (e4) allele of the apolipoprotein E (ApoE) gene has been implicated as a major risk factor in this process. The aim of this FDG-PET study was to assess the ApoE e4 dose related effect on regional cerebral glucose metabolism (METglc) in clinical AD patients, with statistical voxel based methods. Methods: Eighty six consecutive mild to moderate AD patients included in the Network for Efficiency and Standardisation of Dementia Diagnosis database underwent FDG-PET scans at rest. PCR was used to determine the ApoE genotype. Patients were grouped as e4 non-carriers (n = 46), e3/e4 (n = 27) and e4/ e4 (n = 13) carriers. A voxel-based mapping program was used to compare each AD subgroup with a database of 35 sex and age matched controls (p,0.001, corrected for cluster extent) and also to compare between the subgroups (p,0.001, uncorrected). Results: No difference was found as to age at examination, age at onset, sex, disease duration, educational level, or severity of dementia between AD subgroups. Compared with controls, all AD subgroups had equivalent METglc reductions in the precuneus, posterior cingulate, parietotemporal, and frontal regions. Direct comparisons between AD subgroups indicated that patients with at least one e4 allele had METglc reductions within additional associative and limbic areas compared with e4 noncarriers.Conclusions: The present FDG-PET study showed different metabolic phenotypes related to the ApoE genotype in clinical AD patients, as revealed with voxel based statistical methods. The results suggest a generalised disorder in e4 carriers impairing metabolism globally, in addition to the more localised changes typical of AD patients.

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“…Neuroimaging studies may shed additional light on the association between ApoE e4 and psychotic manifestations of AD. One in vivo SPECT study has suggested that delusions in AD may be associated with hypoperfusion in the temporal lobes (Starkstein et al, 1994), and some (Lee et al, 2003) but not all (van Dyck et al, 1998) functional imaging studies have shown that AD patients who carry the e4 allele have reduced temporal lobe function. The structural MRI literature is more unified in showing greater medial temporal lobe atrophy in association with the e4 allele in AD (Lehtovirta et al, 1996b;Hashimoto et al, 2001;Basso et al, in press).…”

Section: Interpretation Of An Increased Risk Of Psychosis In Apoe E4 mentioning

confidence: 99%

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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Absence of an Apolipoprotein E ϵ4 Allele Is Associated With Increased Parietal Regional Cerebral Blood Flow Asymmetry in Alzheimer Disease

Abstract: Greater parietal rCBF asymmetry is involved in epsilon4- AD than in epsilon4+ AD. Lack of the epsilon4 allele may be associated with other (as yet undiscovered) genetic or environmental risk factors, which confer greater neuropathological asymmetry.

Cited by 30 publications

References 34 publications

Apolipoprotein E ε4 Allele Is Unrelated to Cognitive or Functional Decline in Alzheimer’s Disease: Retrospective and Prospective Analysis

Apolipoprotein E ε4 Allele Is Unrelated to Cognitive or Functional Decline in Alzheimer’s Disease: Retrospective and Prospective Analysis

Brain metabolic decreases related to the dose of the ApoE e4 allele in Alzheimer's disease

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

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