Apolipoprotein E and cognitive performance: a meta-analysis.

The epsilon4 allele of the apolipoprotein E (APOE) gene is a known risk factor for Alzheimer's disease and may also affect cognitive performance in normal aging. Evidence of the presence and magnitude of epsilon4-related cognitive deficits was examined with a meta-analysis of the available literature. Thirty-eight studies were included, and cognitive performance was collapsed into 8 domains. Results indicated significant APOE-epsilon4 group differences for global cognitive functioning, episodic memory, and executive functioning, in favor of non-epsilon4 carriers. In addition, older age and APOE-epsilon4 heterozygosity was associated with smaller epsilon4-related impairments. The meta-analysis results suggest that APOE-epsilon4 genotype does affect cognitive performance in healthy aging, although the influence is relatively small and specific to certain domains of cognitive performance.

[1]  H. Christensen,et al.  Change in cognitive functioning associated with apoE genotype in a community sample of older adults. , 2002, Psychology and aging.

[2]  J. Woo,et al.  Apolipoprotein E ε4 allele is not associated with the cognitive impairment in community‐dwelling normal elderly individuals , 2002 .

[3]  David A Bennett,et al.  The apolipoprotein E epsilon 4 allele and decline in different cognitive systems during a 6-year period. , 2002, Archives of neurology.

[4]  Hiroaki Kazui,et al.  Apolipoprotein E ε4 and the pattern of regional brain atrophy in Alzheimer’s disease , 2001, Neurology.

[5]  K. Horsburgh,et al.  The role of apolipoprotein E in Alzheimer’s disease, acute brain injury and cerebrovascular disease: evidence of common mechanisms and utility of animal models , 2000, Neurobiology of Aging.

[6]  Jacob Cohen Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[7]  J. Haines,et al.  Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis , 1997 .

[8]  A. Roses,et al.  Cognitive function and apolipoprotein E in very old adults: findings from the Nun Study. , 2000, The journals of gerontology. Series B, Psychological sciences and social sciences.

[9]  M. Pericak-Vance,et al.  Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[10]  E. Helkala,et al.  Associations between apolipoprotein E phenotype, glucose metabolism and cognitive function in men. An explorative study in a population sample , 2001, Diabetic medicine : a journal of the British Diabetic Association.

[11]  C. Jonker,et al.  APOE-ε4 is associated with memory decline in cognitively impaired elderly , 2000, Neurology.

[12]  H. Soininen,et al.  Clinical and neuropsychological characteristics in familial and sporadic Alzheimer's disease , 1996, Neurology.

[13]  J. Fisk,et al.  APOE Genotype, Memory Test Performance, and the Risk of Alzheimer’s Disease in the Canadian Study of Health and Aging , 2002, Dementia and Geriatric Cognitive Disorders.

[14]  R. Reitan,et al.  The Halstead-Reitan neuropsychological test battery: Theory and clinical interpretation , 1993 .

[15]  S. Houle,et al.  Activation of medial temporal structures during episodic memory retrieval , 1996, Nature.

[16]  P. Doraiswamy,et al.  Learning and recall in subjects at genetic risk for Alzheimer's disease. , 2002, The Journal of neuropsychiatry and clinical neurosciences.

[17]  J. Yesavage,et al.  The APOE ∍4 allele Is Associated with Decline on Delayed Recall Performance in Community‐Dwelling Older Adults , 1998 .

[18]  Akira Homma,et al.  Reduced size of right hippocampus in 39- to 80-year-old normal subjects carrying the apolipoprotein E ϵ4 allele , 1997, Neuroscience Letters.

[19]  R. Sulkava,et al.  Does Apolipoprotein E Influence Learning and Memory in the Nondemented Oldest Old? , 2001, International Psychogeriatrics.

[20]  Jonathan D. Smith,et al.  Apolipoproteins and aging: emerging mechanisms , 2002, Ageing Research Reviews.

[21]  J. Haines,et al.  Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. , 1997, JAMA.

[22]  H. Soininen,et al.  Volumes of hippocampus, amygdala and frontal lobe in Alzheimer patients with different apolipoprotein E genotypes , 1995, Neuroscience.

[23]  J. Cauley,et al.  Apolipoprotein E phenotype and cognitive decline in a prospective study of elderly community women. , 1997, Archives of neurology.

[24]  M. C. Newman,et al.  Talkativeness in Cognitively Normal Women at Genetic Risk for Alzheimer’s Disease , 2000 .

[25]  F. Fazekas,et al.  Apolipoprotein E4allele in the normal elderly: neuropsychologic and brain MRI correlates , 1996, Clinical genetics.

[26]  L. Hedges,et al.  Statistical Methods for Meta-Analysis , 1987 .

[27]  R. Plomin,et al.  No association between apolipoprotein E polymorphisms and general cognitive ability in children , 2001, Neuroscience Letters.

[28]  W. Jagust,et al.  The Role of APOE ∊4 in Modulating Effects of Other Risk Factors for Cognitive Decline in Elderly Persons , 1999 .

[29]  H. Christensen,et al.  Education, Activity, Health, Blood Pressure and Apolipoprotein E as Predictors of Cognitive Change in Old Age: A Review , 2000, Gerontology.

[30]  Caroline Hayward,et al.  Ageing: Cognitive change and the APOE ɛ4 allele , 2002, Nature.

[31]  J. Flory,et al.  Memory performance and the apolipoprotein E polymorphism in a community sample of middle-aged adults. , 2000, American journal of medical genetics.

[32]  L. Bäckman,et al.  Three-year changes in cognitive performance as a function of apolipoprotein E genotype: evidence from very old adults without dementia. , 1998, Psychology and aging.

[33]  J. Mortimer,et al.  Is APOE-ε4 a risk factor for cognitive impairment in normal aging? , 2000, Neurology.

[34]  A. M. Saunders,et al.  Apolipoprotein E ϵ4 allele and hippocampal volume in twins with normal cognition , 1997, Neurology.

[35]  L. Squire Mechanisms of memory. , 1986, Lancet.

[36]  K. Manton,et al.  Apolipoprotein E genotype determines survival in the oldest old (85 years or older) who have good cognition. , 1996, Archives of neurology.

[37]  N Butters,et al.  Episodic memory changes are associated with the APOE- epsilon 4 allele in nondemented older adults , 1995, Neurology.

[38]  V. Bowden,et al.  The Journal of Neuropsychiatry and Clinical Neurosciences , 1992 .

[39]  David A. Bennett,et al.  The apolipoprotein E ε2 allele and decline in episodic memory , 2002 .

[40]  J. Nici,et al.  A Compendium of Neuropsychological Tests, 2nd ed , 2000 .

[41]  F. Lalonde,et al.  Context-specific memory and apolipoprotein E (ApoE) ε4: Cognitive evidence from the NIMH prospective study of risk for Alzheimer's disease , 2004, Journal of the International Neuropsychological Society.

[42]  E. L. Mortensen,et al.  A gender difference in the association between APOE genotype and age-related cognitive decline , 2001, Neurology.

[43]  T. Sunderland,et al.  Working memory and apolipoprotein E: What’s the connection? , 2002, Neuropsychologia.

[44]  Eric M. Reiman,et al.  Preclinical memory decline in cognitively normal apolipoprotein E–ε4 homozygotes , 1999, Neurology.

[45]  Richard J. Caselli,et al.  Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: a replication study , 2001, Journal of the Neurological Sciences.

[46]  L. Thal,et al.  Neuropsychological function and apolipoprotein E genotype in the preclinical detection of Alzheimer's disease. , 1999, Psychology and aging.

[47]  A. Saykin,et al.  The relationship of APOE genotype to neuropsychological performance in long‐term cancer survivors treated with standard dose chemotherapy , 2003, Psycho-oncology.

[48]  E G Tangalos,et al.  Hippocampal atrophy and apolipoprotein E genotype are independently associated with Alzheimer's disease , 1998, Annals of neurology.

[49]  H. Jacqmin-Gadda,et al.  Longitudinal analysis of the effect of apolipoprotein E ε4 and education on cognitive performance in elderly subjects: the PAQUID study , 2002, Journal of neurology, neurosurgery, and psychiatry.

[50]  G. Assmann,et al.  Apolipoprotein E Polymorphism and Coronary Artery Disease , 1983, Arteriosclerosis.

[51]  F. Lalonde,et al.  Effect of apolipoprotein E genotype on hippocampal volume loss in aging healthy women , 2001, Neurology.

[52]  G. Alexander,et al.  A distinctive interaction between memory and chronic daytime somnolence in asymptomatic APOE e4 homozygotes. , 2002, Sleep.

[53]  H. Soininen,et al.  Longitudinal SPECT study in Alzheimer’s disease: relation to apolipoprotein E polymorphism , 1998, Journal of neurology, neurosurgery, and psychiatry.

[54]  M. Laakso,et al.  The association of apolipoprotein E polymorphism with memory: a population based study , 1995, Neuroscience Letters.

[55]  W. White,et al.  Preliminary report of a genetic basis for cognitive decline after cardiac operations. The Neurologic Outcome Research Group of the Duke Heart Center. , 1997, The Annals of thoracic surgery.

[56]  Mark S. Cohen,et al.  Patterns of brain activation in people at risk for Alzheimer's disease. , 2000, The New England journal of medicine.

[57]  J. M. Guralnik,et al.  The role of APOE-&egr;4 in longitudinal cognitive decline: MacArthur Studies of Successful Aging , 2003 .

[58]  K. Welsh-Bohmer,et al.  APOE-ε4 count predicts age when prevalence of AD increases, then declines , 1999, Neurology.

[59]  S. Corkin,et al.  Apolipoprotein E genotype does not influence rates of cognitive decline in Alzheimer's disease , 1996, Neurology.

[60]  I. Deary,et al.  The influence of the e4 allele of the apolipoprotein E gene on childhood IQ, nonverbal reasoning in old age, and lifetime cognitive change , 2003 .

[61]  P. Amouyel,et al.  Early effect of ApoE-ϵ4 allele on cognitive results in a group of highly performing subjects: the EVA study , 1996, Neuroscience Letters.

[62]  P. Rabbitt,et al.  Apolipoprotein E genotype does not predict decline in intelligence in healthy older adults , 2002, Neuroscience Letters.

[63]  P. Visscher,et al.  Apolipoprotein e gene variability and cognitive functions at age 79: a follow-up of the Scottish mental survey of 1932. , 2004, Psychology and aging.

[64]  M. Laakso,et al.  Memory functions in human subjects with different apolipoprotein E phenotypes during a 3-year population-based follow-up study , 1996, Neuroscience Letters.

[65]  R. Mahley,et al.  Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. , 1988, Science.

[66]  R. Parasuraman,et al.  The apolipoprotein E gene, attention, and brain function. , 2002, Neuropsychology.

[67]  J. Vaupel,et al.  Estimation of apolipoprotein E genotype‐specific relative mortality risks from the distribution of genotypes in centenarians and middle‐aged men: Apolipoprotein E gene is a “frailty gene,” not a “longevity gene” , 2000, Genetic epidemiology.

[68]  S. Resnick,et al.  Longitudinal change in hippocampal volume as a function of apolipoprotein E genotype , 2000, Neurology.

[69]  R. Sulkava,et al.  Apolipoprotein E, Cognitive Function, and Dementia in a General Population Aged 85 Years and Over , 2000, International Psychogeriatrics.

[70]  F B ROGERS,et al.  Medical Subject Headings , 1948, Nature.

[71]  D. Easton,et al.  Apolipoprotein E4 is only a weak predictor of dementia and cognitive decline in the general population , 2002, Journal of medical genetics.

[72]  M. Lezak Neuropsychological assessment, 3rd ed. , 1995 .

[73]  E G Tangalos,et al.  Apolipoprotein E genotype influences cognitive ‘phenotype’ in patients with Alzheimer's disease but not in healthy control subjects , 1998, Neurology.

[74]  A Hofman,et al.  Hippocampal, amygdalar, and global brain atrophy in different apolipoprotein E genotypes , 2002, Neurology.

[75]  J. Haines,et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. , 1993, Science.

[76]  H. Soininen,et al.  Major decrease in the volume of the entorhinal cortex in patients with Alzheimer’s disease carrying the apolipoprotein E ε4 allele , 1998, Journal of neurology, neurosurgery, and psychiatry.