Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe

Background: Blood pressure level is associated with the risk of clinical Alzheimer disease (AD), yet the underlying mechanisms are unclear. High blood pressure levels may cause cerebral small-vessel pathology, which contributes to cognitive decline in patients with AD. Alternatively, in persons with high blood pressure, increased numbers of neurofibrillary tangles and amyloid plaques at autopsy have also been observed, suggesting direct links between blood pressure and AD. Objective: To investigate the association of blood pressure and markers of small-vessel disease (white matter lesions [WMLs] on MRI) with hippocampal and amygdalar atrophy on MRI—potential in vivo indicators of Alzheimer pathology. Methods: In 1995 to 1996, 511 nondemented elderly subjects (age 60 to 90) underwent MRI. The extent of WMLs was assessed, and volumes of the hippocampus and amygdala were measured. Blood pressure levels were assessed at the time of MRI and 5 years before the MRI. Results: Higher diastolic blood pressure 5 years before MRI predicted more hippocampal atrophy in persons untreated for hypertension (per SD increase −0.10 mL [95% CI −0.19 to −0.02, p = 0.02]). Conversely, in persons treated for hypertension, a low diastolic blood pressure was associated with more severe atrophy. Persons with more WMLs on MRI more often had severe atrophy of the hippocampus and amygdala. Conclusion: Blood pressure and indicators of small-vessel disease in the brain may be associated with atrophy of structures affected by Alzheimer pathology.

[1]  A Hofman,et al.  Homocysteine and brain atrophy on MRI of non-demented elderly. , 2003, Brain : a journal of neurology.

[2]  Henrique Sequeira,et al.  Activation of ventrolateral medullary neurons projecting to spinal autonomic areas after chemical stimulation of the central nucleus of amygdala: a neuroanatomical study in the rat , 2001, Brain Research.

[3]  A. Hofman,et al.  Cerebral white matter lesions and cognitive function: The Rotterdam scan study , 2000, Annals of neurology.

[4]  D. Bennett,et al.  The cross-sectional association between blood pressure and Alzheimer's disease in a biracial community population of older persons. , 2000, The journals of gerontology. Series A, Biological sciences and medical sciences.

[5]  N. Lassen,et al.  White matter magnetic resonance hyperintensities in dementia of the Alzheimer type: morphological and regional cerebral blood flow correlates. , 1994, Journal of neurology, neurosurgery, and psychiatry.

[6]  B. Winblad,et al.  Low blood pressure and risk of dementia in the Kungsholmen project: a 6-year follow-up study. , 2003, Archives of neurology.

[7]  A. Hofman,et al.  Association of diabetes mellitus and dementia: The Rotterdam Study , 1996, Diabetologia.

[8]  Arno W. Hoes,et al.  Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. , 1997, Circulation.

[9]  Matthijs Oudkerk,et al.  Incidence and Risk Factors of Silent Brain Infarcts in the Population-Based Rotterdam Scan Study , 2003, Stroke.

[10]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[11]  T. Bekinschtein,et al.  White matter hyperintensities are significantly associated with cortical atrophy in Alzheimer’s disease , 2004, Journal of Neurology, Neurosurgery & Psychiatry.

[12]  D. Royall,et al.  Alzheimer disease as a vascular disorder: nosological evidence. , 2002, Stroke.

[13]  Matthijs Oudkerk,et al.  Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam scan study , 2002, Annals of neurology.

[14]  A. Hofman,et al.  Determinants of disease and disability in the elderly: The Rotterdam elderly study , 1991, European Journal of Epidemiology.

[15]  B. Winblad,et al.  Low blood pressure and dementia in elderly people: the Kungsholmen project , 1996, BMJ.

[16]  Leonardo Pantoni,et al.  Pathophysiology of Age-Related Cerebral White Matter Changes , 2002, Cerebrovascular Diseases.

[17]  J. C. Torre,et al.  Critically attained threshold of cerebral hypoperfusion: the CATCH hypothesis of Alzheimer’s pathogenesis , 2000, Neurobiology of Aging.

[18]  D. Bennett,et al.  Association of incident Alzheimer disease and blood pressure measured from 13 years before to 2 years after diagnosis in a large community study. , 2001, Archives of neurology.

[19]  M. Breteler Vascular Involvement in Cognitive Decline and Dementia: Epidemiologic Evidence from the Rotterdam Study and the Rotterdam Scan Study , 2000, Annals of the New York Academy of Sciences.

[20]  M. Ursino,et al.  Relationships among cerebral perfusion pressure, autoregulation, and transcranial Doppler waveform: a modeling study. , 1998, Journal of neurosurgery.

[21]  O. Paulson,et al.  Regulation of cerebral blood flow in health and disease. , 1992, Journal of cardiovascular pharmacology.

[22]  G. Halliday,et al.  Patients with vascular dementia due to microvascular pathology have significant hippocampal neuronal loss , 2002, Journal of neurology, neurosurgery, and psychiatry.

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

[24]  C. DeCarli,et al.  Association of midlife blood pressure to late-life cognitive decline and brain morphology , 1998, Neurology.

[25]  A. Hofman,et al.  Silent brain infarcts and the risk of dementia and cognitive decline. , 2003, The New England journal of medicine.

[26]  R. Mayeux,et al.  The relationship of hypertension in the elderly to AD, vascular dementia, and cognitive function , 2002, Neurology.

[27]  Tom den Heijer,et al.  Association between blood pressure levels over time and brain atrophy in the elderly , 2003, Neurobiology of Aging.

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

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

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

[31]  Frederik Barkhof,et al.  White matter lesions and hippocampal atrophy in Alzheimer’s disease , 2004, Neurology.

[32]  W. Burke,et al.  Blood pressure regulation in Alzheimer's disease. , 1994, Journal of the autonomic nervous system.

[33]  Ian G. McKeith,et al.  Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales , 2001, The Lancet.

[34]  I. Skoog,et al.  Hypertension and Related Factors in the Etiology of Alzheimer's Disease , 2002, Annals of the New York Academy of Sciences.

[35]  C. Jack,et al.  Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia , 2002, Neurology.

[36]  I. Skoog Highs and lows of blood pressure: a cause of Alzheimer's disease? , 2003, The Lancet Neurology.

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

[38]  L. Hansson,et al.  Hypertension is related to cognitive impairment: a 20-year follow-up of 999 men. , 1998, Hypertension.

[39]  W. M. van der Flier,et al.  Interaction of medial temporal lobe atrophy and white matter hyperintensities in AD , 2004, Neurology.

[40]  B. Pappas,et al.  Hippocampal nitric oxide upregulation precedes memory loss and Aβ 1-40 accumulation after chronic brain hypoperfusion in rats , 2003, Neurological research.

[41]  C. Dufouil,et al.  Cognitive decline in individuals with high blood pressure , 1999, Neurology.

[42]  Nick C Fox,et al.  Assessing the onset of structural change in familial Alzheimer's disease , 2003, Annals of neurology.

[43]  A Hofman,et al.  A follow‐up study of blood pressure and cerebral white matter lesions , 1999, Annals of neurology.

[44]  R. Havlik,et al.  Midlife blood pressure and dementia: the Honolulu–Asia aging study☆ , 2000, Neurobiology of Aging.

[45]  J. C. Torre,et al.  Alzheimer Disease as a Vascular Disorder: Nosological Evidence , 2002 .

[46]  D. Sparks,et al.  Increased density of senile plaques (SP), but not neurofibrillary tangles (NFT), in non-demented individuals with the apolipoprotein E4 allele: comparison to confirmed Alzheimer's disease patients , 1996, Journal of the Neurological Sciences.

[47]  W. Markesbery,et al.  Hippocampal volume as an index of Alzheimer neuropathology: Findings from the Nun Study , 2002, Neurology.

[48]  S. Black,et al.  Beyond the hippocampus , 2001, Neurology.

[49]  A. Korczyn Mixed Dementia—the Most Common Cause of Dementia , 2002, Annals of the New York Academy of Sciences.

[50]  A. Hofman,et al.  Blood Pressure and Risk of Dementia: Results from the Rotterdam Study and the Gothenburg H-70 Study , 2000, Dementia and Geriatric Cognitive Disorders.

[51]  A. Hofman,et al.  Prevalence and Risk Factors of Silent Brain Infarcts in the Population-Based Rotterdam Scan Study , 2002, Stroke.

[52]  O B Paulson,et al.  Cerebral autoregulation. , 1984, Stroke.