You are seeing this message because your Web browser does not support basic Web standards. Find out more about why this message is appearing and what you can do to make your experience on this site better.


ABOUT JAMA
Advanced Search

Welcome   | My Account | E-mail Alerts | Access Rights | Sign In


  Vol. 277 No. 10, March 12, 1997 TABLE OF CONTENTS
  JAMA
  •  Online Features
  Original Contributions
 This Article
 •References
 •Full text PDF
 •Send to a friend
 • Save in My Folder
 •Save to citation manager
 •Permissions
 Citing Articles
 •Citation map
 •Citing articles on HighWire
 •Contact me when this article is cited
 Related Content
 •Similar articles in JAMA
 Social Bookmarking
  Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit Add to Technorati Add to Twitter What's this?

Brain Infarction and the Clinical Expression of Alzheimer Disease

The Nun Study

David A. Snowdon, PhD; Lydia H. Greiner, BSN; James A. Mortimer, PhD; Kathryn P. Riley, PhD; Philip A. Greiner, DNSc; William R. Markesbery, MD

JAMA. 1997;277(10):813-817.


Abstract

Objective.
—To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD).

Design.
—Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD.

Setting.
—Convents in the Midwestern, Eastern, and Southern United States.

Participants.
—A total of 102 college-educated women aged 76 to 100 years.

Main Outcome Measures.
—Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria.

Results.
—Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7,95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts.

Conclusion.
—These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.



Author Affiliations

From the Sanders-Brown Center on Aging (Drs Snowdon, Riley, and Markesbery, and Ms Greiner), and the Departments of Preventive Medicine (Drs Snowdon and Riley), Pathology (Dr Markesbery), and Neurology (Dr Markesbery), College of Medicine, University of Kentucky, Lexington; the Institute on Aging, University of South Florida, Tampa (Dr Mortimer); and the School of Nursing, Fairfield University, Fairfield, Conn (Dr Greiner).


Footnotes

Reprints: David A. Snowdon, PhD, Sanders-Brown Center on Aging, University of Kentucky, 101 Sanders-Brown Bldg, Lexington, KY 40536-0230.



Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Differential Impact of Lacunes and Microvascular Lesions on Poststroke Depression
Santos et al.
Stroke 2009;40:3557-3562.
ABSTRACT | FULL TEXT  

CSF biomarkers predict rate of cognitive decline in Alzheimer disease
Kester et al.
Neurology 2009;73:1353-1358.
ABSTRACT | FULL TEXT  

Diabetes is associated with a slower rate of cognitive decline in Alzheimer disease
Sanz et al.
Neurology 2009;73:1359-1366.
ABSTRACT | FULL TEXT  

Preventing dementia: role of vascular risk factors and cerebral emboli
Purandare
Br Med Bull 2009;91:49-59.
ABSTRACT | FULL TEXT  

Poststroke dementia predicts poor survival in long-term follow-up: influence of prestroke cognitive decline and previous stroke
Melkas et al.
J. Neurol. Neurosurg. Psychiatry 2009;80:865-870.
ABSTRACT | FULL TEXT  

Cognitive impairment risk: White matter hyperintensity progression matters
Silbert et al.
Neurology 2009;73:120-125.
ABSTRACT | FULL TEXT  

{beta}-Amyloid, Blood Vessels, and Brain Function
Smith and Greenberg
Stroke 2009;40:2601-2606.
ABSTRACT | FULL TEXT  

Current Concepts in Vascular Cognitive Impairment and Pharmacotherapeutic Implications
Rojas-Fernandez and Moorhouse
The Annals of Pharmacotherapy 2009;43:1310-1323.
ABSTRACT | FULL TEXT  

Leisure Activities and Risk of Vascular Cognitive Impairment in Older Adults
Verghese et al.
J Geriatr Psychiatry Neurol 2009;22:110-118.
ABSTRACT  

Association of Prior Stroke With Cognitive Function and Cognitive Impairment: A Population-Based Study
Knopman et al.
Arch Neurol 2009;66:614-619.
ABSTRACT | FULL TEXT  

Early Age-Related Macular Degeneration, Cognitive Function, and Dementia: The Cardiovascular Health Study
Baker et al.
Arch Ophthalmol 2009;127:667-673.
ABSTRACT | FULL TEXT  

Risk of dementia in MCI: Combined effect of cerebrovascular disease, volumetric MRI, and 1H MRS
Kantarci et al.
Neurology 2009;72:1519-1525.
ABSTRACT | FULL TEXT  

Age-associated leukoaraiosis and cortical cholinergic deafferentation
Bohnen et al.
Neurology 2009;72:1411-1416.
ABSTRACT | FULL TEXT  

Contribution of Vascular Risk Factors to the Progression in Alzheimer Disease
Helzner et al.
Arch Neurol 2009;66:343-348.
ABSTRACT | FULL TEXT  

Interhemispheric Distribution of Alzheimer Disease and Vascular Pathology in Brain Aging
Giannakopoulos et al.
Stroke 2009;40:983-986.
ABSTRACT | FULL TEXT  

Regional White Matter Integrity Differentiates Between Vascular Dementia and Alzheimer Disease
Zarei et al.
Stroke 2009;40:773-779.
ABSTRACT | FULL TEXT  

Understanding White Matter Disease: Imaging-Pathological Correlations in Vascular Cognitive Impairment
Black et al.
Stroke 2009;40:S48-S52.
ABSTRACT | FULL TEXT  

An inverse association of cardiovascular risk and frontal lobe glucose metabolism
Kuczynski et al.
Neurology 2009;72:738-743.
ABSTRACT | FULL TEXT  

Alzheimer's disease
Burns and Iliffe
BMJ 2009;338:b158-b158.
FULL TEXT  

MRI Biomarkers of Vascular Damage and Atrophy Predicting Mortality in a Memory Clinic Population
Henneman et al.
Stroke 2009;40:492-498.
ABSTRACT | FULL TEXT  

Vascular risk factors and dementia: How to move forward?
Viswanathan et al.
Neurology 2009;72:368-374.
ABSTRACT | FULL TEXT  

Cerebrovascular Dysfunction in Amyloid Precursor Protein Transgenic Mice: Contribution of Soluble and Insoluble Amyloid-{beta} Peptide, Partial Restoration via {gamma}-Secretase Inhibition
Han et al.
J. Neurosci. 2008;28:13542-13550.
ABSTRACT | FULL TEXT  

Childhood cognitive ability and risk of late-onset Alzheimer and vascular dementia
McGurn et al.
Neurology 2008;71:1051-1056.
ABSTRACT | FULL TEXT  

Galantamine treatment in Alzheimer's disease with cerebrovascular disease: responder analyses from a randomized, controlled trial (GAL-INT-6)
Erkinjuntti et al.
J Psychopharmacol 2008;22:761-768.
ABSTRACT  

Measuring Cerebral Atrophy and White Matter Hyperintensity Burden to Predict the Rate of Cognitive Decline in Alzheimer Disease
Brickman et al.
Arch Neurol 2008;65:1202-1208.
ABSTRACT | FULL TEXT  

Apolipoprotein E {varepsilon}4 Allele Genotype and the Effect of Depressive Symptoms on the Risk of Dementia in Men: The Honolulu-Asia Aging Study
Irie et al.
Arch Gen Psychiatry 2008;65:906-912.
ABSTRACT | FULL TEXT  

Lacunar infarcts: no black holes in the brain are benign
Norrving
PN 2008;8:222-228.
ABSTRACT | FULL TEXT  

Hypoxia and Alzheimer disease
Patterson
CMAJ 2008;178:1687-1688.
FULL TEXT  

The Inhalation Anesthetic Desflurane Induces Caspase Activation and Increases Amyloid {beta}-Protein Levels under Hypoxic Conditions
Zhang et al.
J. Biol. Chem. 2008;283:11866-11875.
ABSTRACT | FULL TEXT  

Cognitive and Anatomic Contributions of Metabolic Decline in Alzheimer Disease and Cerebrovascular Disease
Kuczynski et al.
Arch Neurol 2008;65:650-655.
ABSTRACT | FULL TEXT  

Amyloid-Associated Depression: A Prodromal Depression of Alzheimer Disease?
Sun et al.
Arch Gen Psychiatry 2008;65:542-550.
ABSTRACT | FULL TEXT  

Comparability of the Clinical Diagnostic Criteria for Vascular Dementia: A Critical Review. Part I
Wiederkehr et al.
J. Neuropsychiatry Clin. Neurosi. 2008;20:150-161.
ABSTRACT | FULL TEXT  

Diagnosis and treatment of dementia: 2. Diagnosis
Feldman et al.
CMAJ 2008;178:825-836.
ABSTRACT | FULL TEXT  

Altered morphology and 3D architecture of brain vasculature in a mouse model for Alzheimer's disease
Meyer et al.
Proc. Natl. Acad. Sci. USA 2008;105:3587-3592.
ABSTRACT | FULL TEXT  

The Cerebrovascular Pathology in Alzheimer's Disease and Its Influence on Clinical Variables
Modrego et al.
AM J ALZHEIMERS DIS OTHER DEMEN 2008;23:91-96.
ABSTRACT  

11C PiB and structural MRI provide complementary information in imaging of Alzheimer's disease and amnestic mild cognitive impairment
Jack et al.
Brain 2008;131:665-680.
ABSTRACT | FULL TEXT  

Linking MRI Hyperintensities With Patterns of Neuropsychological Impairment: Evidence for a Threshold Effect
Libon et al.
Stroke 2008;39:806-813.
ABSTRACT | FULL TEXT  

Gray Matter Atrophy in Patients With Ischemic Stroke With Cognitive Impairment
Stebbins et al.
Stroke 2008;39:785-793.
ABSTRACT | FULL TEXT  

Untangling Vascular Cognitive Impairment
Merino
Stroke 2008;39:739-740.
FULL TEXT  

Is amnestic mild cognitive impairment always AD?
Jagust
Neurology 2008;70:502-503.
FULL TEXT  

Abnormal Regional Cerebral Blood Flow in Cognitively Normal Elderly Subjects With Hypertension
Dai et al.
Stroke 2008;39:349-354.
ABSTRACT | FULL TEXT  

Diagnosis and treatment of dementia: Introduction. Introducing a series based on the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia
Chertkow
CMAJ 2008;178:316-321.
FULL TEXT  

Nox2-derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein
Park et al.
Proc. Natl. Acad. Sci. USA 2008;105:1347-1352.
ABSTRACT | FULL TEXT  

Magnetic Resonance Imaging White Matter Hyperintensities and Brain Volume in the Prediction of Mild Cognitive Impairment and Dementia
Smith et al.
Arch Neurol 2008;65:94-100.
ABSTRACT | FULL TEXT  

Joint effect of stroke and APOE 4 on dementia risk: The Canadian Study of Health and Aging
Jin et al.
Neurology 2008;70:9-16.
ABSTRACT | FULL TEXT  

Mixed brain pathologies account for most dementia cases in community-dwelling older persons
Schneider et al.
Neurology 2007;69:2197-2204.
ABSTRACT | FULL TEXT  

Recurrent lacunar infarction following a previous lacunar stroke: a clinical study of 122 patients
Arboix et al.
J. Neurol. Neurosurg. Psychiatry 2007;78:1392-1394.
ABSTRACT | FULL TEXT  

Progressive Increase in Infarct Size, Neuroinflammation, and Cognitive Deficits in the Presence of High Levels of Amyloid
Whitehead et al.
Stroke 2007;38:3245-3250.
ABSTRACT | FULL TEXT  

Cerebrovascular disease and dementia
KNOPMAN
Br. J. Radiol. 2007;80:S121-S127.
ABSTRACT | FULL TEXT  

Biomarkers of cerebrovascular disease in dementia
MILLS et al.
Br. J. Radiol. 2007;80:S128-S145.
ABSTRACT | FULL TEXT  

Healthy ageing in the Nun Study: definition and neuropathologic correlates
Tyas et al.
Age Ageing 2007;36:650-655.
ABSTRACT | FULL TEXT  

Lobar Distribution of Changes in Gray Matter and White Matter in Memory Clinic Patients: Detected Using Magnetization Transfer Imaging
van Es et al.
Am. J. Neuroradiol. 2007;28:1938-1942.
ABSTRACT | FULL TEXT  

Identification of Alzheimer and vascular lesion thresholds for mixed dementia
Gold et al.
Brain 2007;130:2830-2836.
ABSTRACT | FULL TEXT  

Subcortical Hyperintensities Are Associated With Cognitive Decline in Patients With Mild Cognitive Impairment
Debette et al.
Stroke 2007;38:2924-2930.
ABSTRACT | FULL TEXT  

Tooth loss, dementia and neuropathology in the Nun Study
Stein et al.
Journal of the American Dental Association 2007;138:1314-1322.
ABSTRACT | FULL TEXT  

Age-dependent cerebrovascular dysfunction in a transgenic mouse model of cerebral amyloid angiopathy
Shin et al.
Brain 2007;130:2310-2319.
ABSTRACT | FULL TEXT  

Magnetic Resonance Imaging Predictors of Cognition in Mild Cognitive Impairment
van de Pol et al.
Arch Neurol 2007;64:1023-1028.
ABSTRACT | FULL TEXT  

Retinal Microvascular Signs, Cognitive Function, and Dementia in Older Persons: The Cardiovascular Health Study
Baker et al.
Stroke 2007;38:2041-2047.
ABSTRACT | FULL TEXT  

Transitions to Mild Cognitive Impairments, Dementia, and Death: Findings from the Nun Study
Tyas et al.
Am J Epidemiol 2007;165:1231-1238.
ABSTRACT | FULL TEXT  

Brain Microbleeds and Cognitive Function
Schneider
Stroke 2007;38:1730-1731.
FULL TEXT  

Atrial Fibrillation, Stroke, and Cognition: A Longitudinal Population-Based Study of People Aged 85 and Older
Rastas et al.
Stroke 2007;38:1454-1460.
ABSTRACT | FULL TEXT  

Cortical microinfarcts and demyelination affect cognition in cases at high risk for dementia
Kovari et al.
Neurology 2007;68:927-931.
ABSTRACT | FULL TEXT  

Less Atherosclerosis and Lower Blood Pressure for a Meaningful Life Perspective With More Brain
Staessen et al.
Hypertension 2007;49:389-400.
FULL TEXT  

Serum estradiol and risk of stroke in elderly men
Abbott et al.
Neurology 2007;68:563-568.
ABSTRACT | FULL TEXT  

The Inhalation Anesthetic Isoflurane Induces a Vicious Cycle of Apoptosis and Amyloid {beta}-Protein Accumulation
Xie et al.
J. Neurosci. 2007;27:1247-1254.
ABSTRACT | FULL TEXT  

Course and Causes of Suspected Dementia in Young Adults: A Longitudinal Study
Panegyres and Frencham
AM J ALZHEIMERS DIS OTHER DEMEN 2007;22:48-56.
ABSTRACT  

Strategic Subcortical Hyperintensities in Cholinergic Pathways and Executive Function Decline in Treated Alzheimer Patients
Behl et al.
Arch Neurol 2007;64:266-272.
ABSTRACT | FULL TEXT  

Serum response factor and myocardin mediate arterial hypercontractility and cerebral blood flow dysregulation in Alzheimer's phenotype
Chow et al.
Proc. Natl. Acad. Sci. USA 2007;104:823-828.
ABSTRACT | FULL TEXT  

Education and Alzheimer disease without dementia: Support for the cognitive reserve hypothesis
Roe et al.
Neurology 2007;68:223-228.
ABSTRACT | FULL TEXT  

Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression
Sun et al.
Proc. Natl. Acad. Sci. USA 2006;103:18727-18732.
ABSTRACT | FULL TEXT  

Anterior-medial thalamic lesions in dementia: frequent, and volume dependently associated with sudden cognitive decline
Swartz and Black
J. Neurol. Neurosurg. Psychiatry 2006;77:1307-1312.
ABSTRACT | FULL TEXT  

Relationship of vascular risk to the progression of Alzheimer disease
Regan et al.
Neurology 2006;67:1357-1362.
ABSTRACT | FULL TEXT  

Effect of a clinical stroke on the risk of dementia in a prospective cohort
Gamaldo et al.
Neurology 2006;67:1363-1369.
ABSTRACT | FULL TEXT  

Use of Antidementia Agents in Vascular Dementia: Beyond Alzheimer Disease
Farlow
Mayo Clin Proc. 2006;81:1350-1358.
ABSTRACT | FULL TEXT  

Associations between white matter lesions, cerebrovascular risk factors, and low CSF Abeta42.
Stenset et al.
Neurology 2006;67:830-833.
ABSTRACT | FULL TEXT  

National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards
Hachinski et al.
Stroke 2006;37:2220-2241.
ABSTRACT | FULL TEXT  

Education and the cognitive decline associated with MRI-defined brain infarct
Elkins et al.
Neurology 2006;67:435-440.
ABSTRACT | FULL TEXT  

Age-Related Macular Degeneration and Risk for Stroke
Wong et al.
ANN INTERN MED 2006;145:98-106.
ABSTRACT | FULL TEXT  

Effects of Combination Estrogen Plus Progestin Hormone Treatment on Cognition and Affect
Resnick et al.
J. Clin. Endocrinol. Metab. 2006;91:1802-1810.
ABSTRACT | FULL TEXT  

Postmortem Examination of Vascular Lesions in Cognitive Impairment: A Survey Among Neuropathological Services
Pantoni et al.
Stroke 2006;37:1005-1009.
ABSTRACT | FULL TEXT  

Dementia and Cerebrovascular Disease
Knopman
Mayo Clin Proc. 2006;81:223-230.
ABSTRACT | FULL TEXT  

Plasma {beta}-amyloid and white matter lesions in AD, MCI, and cerebral amyloid angiopathy
Gurol et al.
Neurology 2006;66:23-29.
ABSTRACT | FULL TEXT  

Dissociation of neuropathology from severity of dementia in late-onset Alzheimer disease
Prohovnik et al.
Neurology 2006;66:49-55.
ABSTRACT | FULL TEXT  

Polymorphisms in the PON gene cluster are associated with Alzheimer disease
Erlich et al.
Hum Mol Genet 2006;15:77-85.
ABSTRACT | FULL TEXT  

Genetics of Vascular Cognitive Impairment: The Opportunity and the Challenges
Leblanc et al.
Stroke 2006;37:248-255.
ABSTRACT | FULL TEXT  

Very Early Detection of Alzheimer Neuropathology and the Role of Brain Reserve in Modifying Its Clinical Expression
Mortimer et al.
J Geriatr Psychiatry Neurol 2005;18:218-223.
ABSTRACT  

Lipid lowering agents are associated with a slower cognitive decline in Alzheimer's disease
Masse et al.
J. Neurol. Neurosurg. Psychiatry 2005;76:1624-1629.
ABSTRACT | FULL TEXT  

White Matter Lesions Are Prevalent but Differentially Related With Cognition in Aging and Early Alzheimer Disease
Burns et al.
Arch Neurol 2005;62:1870-1876.
ABSTRACT | FULL TEXT  

Use of laboratory and imaging investigations in dementia
van der Flier and Scheltens
J. Neurol. Neurosurg. Psychiatry 2005;76:v45-v52.
FULL TEXT  

The Pattern of Cognitive Performance in CADASIL: A Monogenic Condition Leading to Subcortical Ischemic Vascular Dementia
Peters et al.
Am. J. Psychiatry 2005;162:2078-2085.
ABSTRACT | FULL TEXT  

Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study
van der Flier et al.
J. Neurol. Neurosurg. Psychiatry 2005;76:1497-1500.
ABSTRACT | FULL TEXT  

NMDA Receptor Activation Inhibits {alpha}-Secretase and Promotes Neuronal Amyloid-{beta} Production
Lesne et al.
J. Neurosci. 2005;25:9367-9377.
ABSTRACT | FULL TEXT  

Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia
Fuh et al.
J. Neurol. Neurosurg. Psychiatry 2005;76:1337-1341.
ABSTRACT | FULL TEXT  

Small Vessel Disease and General Cognitive Function in Nondisabled Elderly: The LADIS Study
van der Flier et al.
Stroke 2005;36:2116-2120.
ABSTRACT | FULL TEXT  





HOME | CURRENT ISSUE | PAST ISSUES | TOPIC COLLECTIONS | CME | SUBMIT | SUBSCRIBE | HELP
CONDITIONS OF USE | PRIVACY POLICY | CONTACT US | SITE MAP
 
© 1997 American Medical Association. All Rights Reserved.