Apolipoprotein E ϵ4 allele is a risk factor for late‐onset Alzheimer's disease and vascular dementia in Han Chinese

Zhang, J. G.; Yang, Jian-Guang; Lin, Zhiyun; He, Lu; Feng, Guoying; Y., X.; Wang, C. F.; Lu, Pi; Song, Shengfang; Dong, Xingtong; Clair, David St; Breen, Gerome

doi:10.1002/gps.330

Cited by 17 publications

(16 citation statements)

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“…Previous reports on an association between ApoE ε4 and VaD have been mixed. [11][12][13][14][15][16][17][18][19] These inconsistencies may be a result of population stratificationsubjects who differ in their ethnic background may possess different genetic susceptibility loci. Also, results of some of the smaller studies may be negative because of inadequate power.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 In addition, the ε4 allele appears to exert maximal effect in patients in whom AD is diagnosed between the ages of 55 and 75. 8,9 The ApoE ε4 allele also has been implicated as a risk factor for vascular dementia (VaD), but the findings have been inconsistent, with some studies showing positive association [10][11][12][13][14] and others not. [15][16][17][18][19] Recently, it has been recognized that patients who have "cognitive impairment but no dementia" (CIND) are an important group at risk for dementia.…”

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confidence: 99%

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Apolipoprotein E 4 genotype as a risk factor for cognitive decline and dementia: data from the Canadian Study of Health and Aging

Hsiung

Sadovnick²,

Feldman³

2004

Canadian Medical Association Journal

148

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Background: Apolipoprotein E (ApoE) ε4 genotype is a wellestablished risk factor for Alzheimer's disease (AD). However, its effect on predicting conversion from normal to "cognitive impairment, no dementia" (CIND) and from CIND to AD is less clear. Methods:We used a nested case-control design from the population-based Canadian Study of Health and Aging (CSHA) to examine the effect of ApoE ε4 genotype on the conversion of subjects from normal to CIND and from CIND to AD. We also contrasted these findings with incident cases of AD and vascular dementia (VaD) in the CSHA cohort. Results: The ApoE ε4 genotype was a significant risk factor for conversion from CIND to AD and from normal to AD and VaD. However, it was not a significant risk factor for conversion from normal to CIND. This effect is robust to adjustment for age, sex and education level. There is significant interaction between the ApoE ε4 genotype and age for AD and for conversion from CIND to AD. No interaction between ApoE ε4 genotype, sex, age, ethnicity and education level was found in other subgroup analyses. The positive predictive value of ApoE ε4 for predicting CIND conversion to AD was 0.48, and the negative predictive value was 0.65. Interpretation: Possession of an ApoE ε4 allele increases the risk of AD developing from CIND. It is also associated with a decrease in the age at onset of AD. Its predictive values do not support its utility as a diagnostic test for predicting progression from CIND to AD, but it may be useful in research studies to enrich study samples that have a higher rate of progression to AD.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Apolipoprotein E 4 genotype as a risk factor for cognitive decline and dementia: data from the Canadian Study of Health and Aging

Hsiung

Sadovnick²,

Feldman³

2004

Canadian Medical Association Journal

148

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“…94,[162][163][164] This problem exists because of overlapping features found in both disorders. For example, AD and VaD share features involving cerebral hypoperfusion, white matter changes, [165][166][167] pathophysiological markers, 168 -172 genetic links, [173][174][175][176] overlapping symptomatology, and diagnostic criteria of dubious reliability. [177][178][179][180][181][182][183][184][185] Several objective clinical criteria are presently used to distinguish AD from VaD, such as the Alzheimer Disease Diagnostic and Treatment Centers, National Institute of Neurological Disorders and StrokeAssociation Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN), DSM-IV, and the Hachinski Ischemia Score.…”

Section: Ad-vad Correlatesmentioning

confidence: 99%

Alzheimer Disease as a Vascular Disorder

Torre

2002

Stroke

777

491

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Background-The main stumbling block in the clinical management and in the search for a cure of Alzheimer disease (AD) is that the cause of this disorder has remained uncertain until now. Summary of Review-Evidence that sporadic (nongenetic) AD is primarily a vascular rather than a neurodegenerative disorder is reviewed. This conclusion is based on the following evidence: (1) epidemiological studies showing that practically all risk factors for AD reported thus far have a vascular component that reduces cerebral perfusion; (2) risk factor association between AD and vascular dementia (VaD); (3) improvement of cerebral perfusion obtained from most pharmacotherapy used to reduce the symptoms or progression of AD; (4) detection of regional cerebral hypoperfusion with the use of neuroimaging techniques to preclinically identify AD candidates; (5) presence of regional brain microvascular abnormalities before cognitive and neurodegenerative changes; (6) common overlap of clinical AD and VaD cognitive symptoms; (7) similarity of cerebrovascular lesions present in most AD and VaD patients; (8) presence of cerebral hypoperfusion preceding hypometabolism, cognitive decline, and neurodegeneration in AD; and (9) confirmation of the heterogeneous and multifactorial nature of AD, likely resulting from the diverse presence of vascular risk factors or indicators of vascular disease. Conclusions-Since the value of scientific evidence generally revolves around probability and chance, it is concluded that the data presented here pose a powerful argument in support of the proposal that AD should be classified as a vascular disorder. According to elementary statistics, the probability or chance that all these findings are due to an indirect pathological effect or to coincidental circumstances related to the disease process of AD seems highly unlikely. The collective data presented in this review strongly support the concept that sporadic AD is a vascular disorder. It is recommended that current clinical management of patients, treatment targets, research designs, and disease prevention efforts need to be critically reassessed and placed in perspective in light of these important findings. Key Words: Alzheimer disease Ⅲ dementia Ⅲ microcirculation Ⅲ risk factors Ⅲ vascular disorders A lzheimer disease (AD) is an insidious disorder that progressively ravages the brain, destroying its memory, intellect, and dignity in the process. The main stumbling block in the clinical management and in the search for a cure of AD is that the cause of this disorder has remained uncertain until now. For more than 30 years, AD has been classified and managed as a neurodegenerative disorder, 1,2 following a report by Roth in 1955 3 that suggested that dementia should be classified into 2 distinct disorders according to the variable mental changes caused by each: vascular dementia (VaD), caused by vascular lesions, and AD, resulting from a neurodegenerative process.Most investigators in the field have supported Roth's notion that dementing processes will d...

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“…The 4 allele of ApoE is associated with an increased risk and earlier onset of AD [5][6][7][8] . The 4 allele has also been associated with VaD, but this association was not reported in every study [8][9][10][11][12][13] . Because many such previous studies were relatively small, we performed a case-control study of 144 VaD patients and 251 control subjects to explore the association of the ApoE exon 4 polymorphism with VaD.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E ε4 Allele Is Associated with Vascular Dementia

Baum

Lam²,

Kwok

et al. 2006

Dement Geriatr Cogn Disord

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Background/Aims: The apolipoprotein E (ApoE) exon 4 polymorphism has been associated with vascular dementia (VaD) risk. Since not all studies confirm this finding, we explored this association in a case-control study. Methods: We genotyped ApoE in 144 VaD patients and 251 controls. Results: VaD patients were more likely than controls to have ApoE Ε3/Ε4 or Ε4/Ε4 genotypes: 23.6% versus 15.1%, odds ratio (OR) = 1.7, p = 0.036. This association remained significant after adjustment for age, sex, hypertension and diabetes by multiple logistic regression: OR = 1.9, p = 0.030. The association of Ε3/Ε4 or Ε4/Ε4 genotypes with VaD was strong among people with hypertension (OR = 2.9, p = 0.007) or diabetes (OR = 6.5, p = 0.011). The association was absent among people without hypertension (OR = 1.1, p = 0.79) or diabetes (OR = 1.3, p = 0.43). Conclusion: This interaction with hypertension and diabetes should be examined in other studies to confirm or refute this observation.

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Apolipoprotein E ϵ4 allele is a risk factor for late‐onset Alzheimer's disease and vascular dementia in Han Chinese

Cited by 17 publications

References 5 publications

Apolipoprotein E 4 genotype as a risk factor for cognitive decline and dementia: data from the Canadian Study of Health and Aging

Apolipoprotein E 4 genotype as a risk factor for cognitive decline and dementia: data from the Canadian Study of Health and Aging

Alzheimer Disease as a Vascular Disorder

Apolipoprotein E ε4 Allele Is Associated with Vascular Dementia

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