Cardiovascular Risk and Hippocampal Thickness in Alzheimer's Disease

Cardiovascular risk factors influence onset and progression of Alzheimer's disease. Among cognitively healthy people, changes in brain structure and function associated with high blood pressure, diabetes, or other vascular risks suggest differential regional susceptibility to neuronal damage. In patients with Alzheimer's disease, hippocampal and medial temporal lobe atrophy indicate early neuronal loss preferentially in key areas for learning and memory. We wanted to investigate whether this regional cortical thinning would be modulated by cardiovascular risk factors. We utilized high-resolution magnetic resonance imaging and a cortical unfolding technique to determine the cortical thickness of medial temporal subregions in 30 patients with Alzheimer's disease. Cardiovascular risk was assessed using a sex-specific multivariable risk score. Greater cardiovascular risk was associated with cortical thinning in the hippocampus CA2/3/dentate gyrus area but not other hippocampal and medial temporal subregions. APOE genotype, a family history of Alzheimer's disease, and age did not influence cortical thickness. Alzheimer's disease-related atrophy could mask the influence of genetic risk factors or age on regional cortical thickness in medial temporal lobe regions, whereas the impact of vascular risk factors remains detectable. This highlights the importance of cardiovascular disease prevention and treatment in patients with Alzheimer's disease.

[1]  A. Simmons,et al.  Regional Magnetic Resonance Imaging Measures for Multivariate Analysis in Alzheimer’s Disease and Mild Cognitive Impairment , 2012, Brain Topography.

[2]  S. Rivest,et al.  The early contribution of cerebrovascular factors to the pathogenesis of Alzheimer’s disease , 2012, The European journal of neuroscience.

[3]  Christian Enzinger,et al.  Vascular Risk Factors, White Matter Hyperintensities and Hippocampal Volume in Normal Elderly Individuals , 2012, Dementia and Geriatric Cognitive Disorders.

[4]  S. Black,et al.  Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association , 2011, Stroke.

[5]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease: Report of the NINCDS—ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease , 2011, Neurology.

[6]  J. Li,et al.  Vascular risk factors promote conversion from mild cognitive impairment to Alzheimer disease , 2011, Neurology.

[7]  H. Hanyu,et al.  Vascular risk factors and progression in Alzheimer's disease , 2011, Geriatrics & gerontology international.

[8]  Bruce Fischl,et al.  Thickness of the human cerebral cortex is associated with metrics of cerebrovascular health in a normative sample of community dwelling older adults , 2011, NeuroImage.

[9]  J. Monsuez,et al.  Cardiovascular Prevention of Cognitive Decline , 2011, Cardiology research and practice.

[10]  Arne D. Ekstrom,et al.  Family history of Alzheimer's disease and hippocampal structure in healthy people. , 2010, The American journal of psychiatry.

[11]  E. Masliah,et al.  Increased BMP6 Levels in the Brains of Alzheimer's Disease Patients and APP Transgenic Mice Are Accompanied by Impaired Neurogenesis , 2010, The Journal of Neuroscience.

[12]  Craig E. L. Stark,et al.  High-resolution structural and functional MRI of hippocampal CA3 and dentate gyrus in patients with amnestic Mild Cognitive Impairment , 2010, NeuroImage.

[13]  P. Hof,et al.  Cardiovascular risk factors affect hippocampal microvasculature in early AD , 2010, Translational neuroscience.

[14]  Magda Tsolaki,et al.  Effect of APOE ε4 allele on cortical thicknesses and volumes: the AddNeuroMed study. , 2010, Journal of Alzheimer's disease : JAD.

[15]  P. Martínez-Martín,et al.  Role of Hypertension in Aggravating Aβ Neuropathology of AD Type and Tau-Mediated Motor Impairment , 2009, Cardiovascular psychiatry and neurology.

[16]  D. Leys,et al.  Treatment of vascular risk factors is associated with slower decline in Alzheimer disease , 2009, Neurology.

[17]  Yaakov Stern,et al.  Physical activity, diet, and risk of Alzheimer disease. , 2009, JAMA.

[18]  M. Kivipelto,et al.  Midlife Serum Cholesterol and Increased Risk of Alzheimer’s and Vascular Dementia Three Decades Later , 2009, Dementia and Geriatric Cognitive Disorders.

[19]  D. Amaral,et al.  The Hippocampal Formation , 2009 .

[20]  Yaakov Stern,et al.  Contribution of vascular risk factors to the progression in Alzheimer disease. , 2009, Archives of neurology.

[21]  Norbert Schuff,et al.  Selective effect of Apo e4 on CA3 and dentate in normal aging and Alzheimer's disease using high resolution MRI at 4 T , 2008, NeuroImage.

[22]  Paul M. Thompson,et al.  Reduced cortical thickness in hippocampal subregions among cognitively normal apolipoprotein E e4 carriers , 2008, NeuroImage.

[23]  C. Stark,et al.  Pattern Separation in the Human Hippocampal CA3 and Dentate Gyrus , 2008, Science.

[24]  M. Pencina,et al.  General Cardiovascular Risk Profile for Use in Primary Care: The Framingham Heart Study , 2008, Circulation.

[25]  Richard J Kryscio,et al.  Transitions to mild cognitive impairments, dementia, and death: findings from the Nun Study. , 2007, American journal of epidemiology.

[26]  H. Braak,et al.  Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry , 2006, Acta Neuropathologica.

[27]  Cheryl L. Dahle,et al.  Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. , 2005, Cerebral cortex.

[28]  L S Honig,et al.  Aggregation of vascular risk factors and risk of incident Alzheimer disease , 2005, Neurology.

[29]  S. Engel,et al.  Dynamics of the Hippocampus During Encoding and Retrieval of Face-Name Pairs , 2003, Science.

[30]  Jan A Staessen,et al.  The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. , 2002, Archives of internal medicine.

[31]  J Tuomilehto,et al.  Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study , 2001, BMJ.

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

[33]  Vascular factors and Alzheimer disease. , 1999, Alzheimer disease and associated disorders.

[34]  L. Hersh,et al.  Insulin-degrading Enzyme Regulates Extracellular Levels of Amyloid β-Protein by Degradation* , 1998, The Journal of Biological Chemistry.

[35]  M. Mullan,et al.  Characteristics of thein VitroVasoactivity of β-Amyloid Peptides , 1998, Experimental Neurology.

[36]  M. Mullan,et al.  Characteristics of the in vitro vasoactivity of beta-amyloid peptides. , 1998, Experimental neurology.

[37]  H. Duvernoy,et al.  The Human Hippocampus: Functional Anatomy, Vascularization and Serial Sections with MRI , 1997 .

[38]  R. Schmidt-Kastner,et al.  Selective vulnerability of the hippocampus in brain ischemia , 1991, Neuroscience.

[39]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.