Jorm AF, Mather KA, Butterworth P, Anstey KJ, Christensen H, Easteal S.
APOE genotype and cognitive functioning in a large age-stratified population sample.
Neuropsychology. 2007 Jan;21(1):1-8.
PubMed.
This is the largest study of its kind and an impressive undertaking. The authors’ findings suggest that some of the age-related cognitive declines implicated in cross-sectional comparisons of persons 20 to 60 years of age are not attributable to the ApoE4 allele or underlying AD pathology.
Additional cross-sectional studies are needed to determine if other neuropsychological tests or cognitive tasks can be used to detect more subtle age-related cognitive declines in ApoE4 carriers. In addition, ongoing longitudinal studies which utilize each person as his or her own control may also provide a more sensitive way to detect effects of the ApoE4 allele on age-related changes in cognitive performance (e.g., Caselli et al., 2004). Since the current report represents only the first-wave assessment from individuals the authors hope to follow for 20 years, they will be able to address this particular question more fully, along with the age at which ApoE4 effects on cognitive decline become more pronounced. Going forward, it is possible that the study will detect cognitive changes closer to the actual age of risk (e.g., 60s in ApoE4 homozygotes, which represent only a small subset of their current sample, and 70s in ApoE4 heterozygotes).
From our perspective, this study also provides further reason to develop brain imaging and other biological markers that track the progressive brain changes associated with the risk of AD prior to the onset of even subtle neuropsychological decline. Such markers also could evaluate promising prevention therapies before the underlying disease is severe enough to have significant cognitive effects. Based on our group’s PET findings in cognitively normal young, late-middle-aged, and young adult ApoE4 carriers, we believe that is an achievable goal (see Reiman et al., 1996; 2001; 2004; and 2005).
References:
Caselli RJ, Reiman EM, Osborne D, Hentz JG, Baxter LC, Hernandez JL, Alexander GG.
Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele.
Neurology. 2004 Jun 8;62(11):1990-5.
PubMed.
Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D.
Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E.
N Engl J Med. 1996 Mar 21;334(12):752-8.
PubMed.
Reiman EM, Caselli RJ, Chen K, Alexander GE, Bandy D, Frost J.
Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease.
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3334-9.
PubMed.
Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, Saunders AM, Hardy J.
Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia.
Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):284-9.
PubMed.
Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, Saunders AM, Hardy J.
Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism.
Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8299-302.
PubMed.
Comments
Arizona Alzheimer's Consortium
This is the largest study of its kind and an impressive undertaking. The authors’ findings suggest that some of the age-related cognitive declines implicated in cross-sectional comparisons of persons 20 to 60 years of age are not attributable to the ApoE4 allele or underlying AD pathology.
Additional cross-sectional studies are needed to determine if other neuropsychological tests or cognitive tasks can be used to detect more subtle age-related cognitive declines in ApoE4 carriers. In addition, ongoing longitudinal studies which utilize each person as his or her own control may also provide a more sensitive way to detect effects of the ApoE4 allele on age-related changes in cognitive performance (e.g., Caselli et al., 2004). Since the current report represents only the first-wave assessment from individuals the authors hope to follow for 20 years, they will be able to address this particular question more fully, along with the age at which ApoE4 effects on cognitive decline become more pronounced. Going forward, it is possible that the study will detect cognitive changes closer to the actual age of risk (e.g., 60s in ApoE4 homozygotes, which represent only a small subset of their current sample, and 70s in ApoE4 heterozygotes).
From our perspective, this study also provides further reason to develop brain imaging and other biological markers that track the progressive brain changes associated with the risk of AD prior to the onset of even subtle neuropsychological decline. Such markers also could evaluate promising prevention therapies before the underlying disease is severe enough to have significant cognitive effects. Based on our group’s PET findings in cognitively normal young, late-middle-aged, and young adult ApoE4 carriers, we believe that is an achievable goal (see Reiman et al., 1996; 2001; 2004; and 2005).
References:
Caselli RJ, Reiman EM, Osborne D, Hentz JG, Baxter LC, Hernandez JL, Alexander GG. Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele. Neurology. 2004 Jun 8;62(11):1990-5. PubMed.
Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, Thibodeau SN, Osborne D. Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon 4 allele for apolipoprotein E. N Engl J Med. 1996 Mar 21;334(12):752-8. PubMed.
Reiman EM, Caselli RJ, Chen K, Alexander GE, Bandy D, Frost J. Declining brain activity in cognitively normal apolipoprotein E epsilon 4 heterozygotes: A foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3334-9. PubMed.
Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, Saunders AM, Hardy J. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):284-9. PubMed.
Reiman EM, Chen K, Alexander GE, Caselli RJ, Bandy D, Osborne D, Saunders AM, Hardy J. Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolism. Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8299-302. PubMed.
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