Effect of plasma lipids, hypertension and APOE genotype on cognitive decline

We examined the combined effect of plasma lipids/hypertension and apolipoprotein E (APOE) genotype on cognitive function in elderly individuals. Plasma concentrations of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), APOE, and history of hypertension were evaluated in 622 community-dwelling individuals aged 65 years and older. We investigated the associations between plasma lipids/hypertension and cognitive function in apolipoprotein E4 allele (APOE4) carrier (E4+) and APOE4 noncarrier (E4-) groups using 3-year longitudinal data. At baseline and 3 years later, cognitive scores were correlated with plasma APOE levels in both E4- and E4+, and HDL level in E4-. The combination of hypertension and E4+, but not E4-, was associated with a significant deterioration in cognitive function during the 3-year follow-up. Our findings suggest that an interaction between APOE and HDL is facilitated by APOE4, and is possibly linked with a protective effect on cognitive decline in later life. The findings also indicate a synergistic effect of an APOE4 allele and hypertension on the acceleration of cognitive decline.

[1]  S. Pr,et al.  Recognition of Alzheimer's disease: the 7 Minute Screen. , 1998 .

[2]  F. Mangialasche,et al.  The pathological cross talk between apolipoprotein E and amyloid-beta peptide in Alzheimer's disease: emerging gene-based therapeutic approaches. , 2010, Journal of Alzheimer's disease : JAD.

[3]  B. Hyman,et al.  Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions , 1993, Neuron.

[4]  R. Havlik,et al.  Joint Effect of the APOE Gene and Midlife Systolic Blood Pressure on Late-Life Cognitive Impairment: The Honolulu-Asia Aging Study , 2001, Stroke.

[5]  H. Buschke,et al.  Screening for dementia by memory testing , 1988, Neurology.

[6]  Aileen B. Sedman,et al.  A longitudinal study , 1987 .

[7]  K. Rye,et al.  Impaired Recycling of Apolipoprotein E4 Is Associated with Intracellular Cholesterol Accumulation* , 2004, Journal of Biological Chemistry.

[8]  Xianlin Han.  The Pathogenic Implication of Abnormal Interaction Between Apolipoprotein E Isoforms, Amyloid-beta Peptides, and Sulfatides in Alzheimer’s Disease , 2010, Molecular Neurobiology.

[9]  Eric M Reiman,et al.  Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment. , 2007, Archives of neurology.

[10]  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.

[11]  Lars Bäckman,et al.  Apolipoprotein E and cognitive performance: a meta-analysis. , 2004, Psychology and aging.

[12]  V. Leoni.  The effect of apolipoprotein E (ApoE) genotype on biomarkers of amyloidogenesis, tau pathology and neurodegeneration in Alzheimer's disease , 2011, Clinical chemistry and laboratory medicine.

[13]  A. D. Roses,et al.  Association of apolipoprotein E allele €4 with late-onset familial and sporadic Alzheimer’s disease , 2006 .

[14]  C. DeCarli,et al.  Predictors of brain morphology for the men of the NHLBI twin study. , 1999, Stroke.

[15]  A. Hofman,et al.  Cerebral white matter lesions, vascular risk factors, and cognitive function in a population‐based study , 1994, Neurology.

[16]  D. Epps,et al.  Isoform-specific interactions of human apolipoprotein E to an intermediate conformation of human Alzheimer amyloid-beta peptide. , 2005, Chemistry and physics of lipids.

[17]  Takashi Asada,et al.  Association between cognitive function and plasma lipids of the elderly after controlling for apolipoprotein E genotype. , 2012, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[18]  L. Bernier,et al.  Apolipoprotein E and atherosclerosis: insight from animal and human studies. , 1999, Clinica chimica acta; international journal of clinical chemistry.

[19]  D. Wechsler.  WAIS-R manual : Wechsler adult intelligence scale-revised , 1981 .

[20]  F. Pfrieger.  Role of cholesterol in synapse formation and function. , 2003, Biochimica et biophysica acta.

[21]  C. Martyn.  Blood pressure and dementia , 1996, The Lancet.

[22]  D. Haskard,et al.  Elevation of Plasma High-Density Lipoprotein Concentration Reduces Interleukin-1–Induced Expression of E-Selectin in an In Vivo Model of Acute Inflammation , 2001, Circulation.

[23]  PhilipR. Wenham,et al.  Apolipoprotein E genotyping by one-stage PCR , 1991, The Lancet.

[24]  J. Heeren,et al.  Recycling of Apoprotein E Is Associated with Cholesterol Efflux and High Density Lipoprotein Internalization* , 2003, The Journal of Biological Chemistry.

[25]  A. Kumar,et al.  Alzheimer's amyloid beta interaction with normal human plasma high density lipoprotein: association with apolipoprotein and lipids. , 1998, Clinica chimica acta; international journal of clinical chemistry.

[26]  D. Sparks,et al.  Increased incidence of neurofibrillary tangles (NFT) in non-demented individuals with hypertension , 1995, Journal of the Neurological Sciences.

[27]  O. F. Olesen,et al.  High Density Lipoprotein Inhibits Assembly of Amyloid β-Peptides into Fibrils , 2000 .

[28]  M. Mattson,et al.  A Mechanism for the Neuroprotective Effect of Apolipoprotein E , 2000, Journal of neurochemistry.

[29]  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.

[30]  R. Kalaria.  The role of cerebral ischemia in Alzheimer’s disease , 2000, Neurobiology of Aging.

[31]  W. Markesbery,et al.  Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS☆ , 2000, Neurobiology of Aging.

[32]  V. Leirer,et al.  Development and validation of a geriatric depression screening scale: a preliminary report. , 1982, Journal of psychiatric research.

[33]  B. Lernfelt,et al.  15-year longitudinal study of blood pressure and dementia , 1996, The Lancet.

[34]  T. Asada,et al.  Dementia and mild cognitive impairment among non-responders to a community survey , 2009, Journal of Clinical Neuroscience.

[35]  A. Roses,et al.  Neurodegeneration in the Central Nervous System of apoE-Deficient Mice , 1995, Experimental Neurology.

[36]  P. Luiten,et al.  Cerebral microvascular pathology in aging and Alzheimer's disease , 2001, Progress in Neurobiology.

[37]  D. Rader,et al.  Reduction of Isoprostanes and Regression of Advanced Atherosclerosis by Apolipoprotein E* , 2001, The Journal of Biological Chemistry.

[38]  W. M. van der Flier,et al.  Joint effect of hypertension and APOE genotype on CSF biomarkers for Alzheimer's disease. , 2010, Journal of Alzheimer's disease : JAD.