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From the Rush Alzheimer’s Disease Center and Rush Institute for Healthy Aging (Drs. Bennett, Wilson, Schneider, Evans, Aggarwal, Barnes, Fox, and J. Bach), and Departments of Neurological Sciences (Drs. Bennett, Wilson, Schneider, Evans, Barnes, Aggarwal, and Fox), Pathology (Dr. Schneider), and Internal Medicine (Dr. Evans), Rush–Presbyterian–St. Luke’s Medical Center, Chicago, IL; and Department of Epidemiology and Preventive Medicine (Dr. Beckett), School of Medicine, University of California at Davis.
Address correspondence and reprint requests to Dr. David A. Bennett, Rush Alzheimer’s Disease Center, 1645 W. Jackson, Suite 675, Chicago, IL 60612; e-mail: dbennett{at}rush.edu
Background: Cognitive abilities of older persons range from normal, to mild cognitive impairment, to dementia. Few large longitudinal studies have compared the natural history of mild cognitive impairment with similar persons without cognitive impairment.
Methods: Participants were older Catholic clergy without dementia, 211 with mild cognitive impairment and 587 without cognitive impairment, who underwent annual clinical evaluation for AD and an assessment of different cognitive abilities. Cognitive performance tests were summarized to yield a composite measure of global cognitive function and separate summary measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. The authors compared the risk of death, risk of incident AD, and rates of change in global cognition and different cognitive domains among persons with mild cognitive impairment to those without cognitive impairment. All models controlled for age, sex, and education.
Results: On average, persons with mild cognitive impairment had significantly lower scores at baseline in all cognitive domains. Over an average of 4.5 years of follow-up, 30% of persons with mild cognitive impairment died, a rate 1.7 times higher than those without cognitive impairment (95% CI, 1.2 to 2.5). In addition, 64 (34%) persons with mild cognitive impairment developed AD, a rate 3.1 times higher than those without cognitive impairment (95% CI, 2.1 to 4.5). Finally, persons with mild cognitive impairment declined significantly faster on measures of episodic memory, semantic memory, and perceptual speed, but not on measures of working memory or visuospatial ability, as compared with persons without cognitive impairment.
Conclusions: Mild cognitive impairment is associated with an increased risk of death and incident AD, and a greater rate of decline in selected cognitive abilities.
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P J Visser, P Scheltens, and F R J Verhey Do MCI criteria in drug trials accurately identify subjects with predementia Alzheimer's disease? J. Neurol. Neurosurg. Psychiatry, October 1, 2005; 76(10): 1348 - 1354. [Abstract] [Full Text] [PDF]
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D. A. Fleischman, R. S. Wilson, J. D. E. Gabrieli, J. A. Schneider, J. L. Bienias, and D. A. Bennett Implicit memory and Alzheimer's disease neuropathology Brain, September 1, 2005; 128(9): 2006 - 2015. [Abstract] [Full Text] [PDF]
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R. C. Petersen and J. C. Morris Mild Cognitive Impairment as a Clinical Entity and Treatment Target Arch Neurol, July 1, 2005; 62(7): 1160 - 1163. [Full Text] [PDF]
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R. C. Petersen, R. G. Thomas, M. Grundman, D. Bennett, R. Doody, S. Ferris, D. Galasko, S. Jin, J. Kaye, A. Levey, et al. Vitamin E and Donepezil for the Treatment of Mild Cognitive Impairment N. Engl. J. Med., June 9, 2005; 352(23): 2379 - 2388. [Abstract] [Full Text] [PDF]
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L. L. Barnes, R. S. Wilson, J. L. Bienias, J. A. Schneider, D. A. Evans, and D. A. Bennett Sex Differences in the Clinical Manifestations of Alzheimer Disease Pathology Arch Gen Psychiatry, June 1, 2005; 62(6): 685 - 691. [Abstract] [Full Text] [PDF]
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T. R. Stoub, M. Bulgakova, S. Leurgans, D. A. Bennett, D. Fleischman, D. A. Turner, and L. deToledo-Morrell MRI predictors of risk of incident Alzheimer disease: A longitudinal study Neurology, May 10, 2005; 64(9): 1520 - 1524. [Abstract] [Full Text] [PDF]
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 P. J. Modrego, N. Fayed, and M. A. Pina Conversion From Mild Cognitive Impairment to Probable Alzheimer's Disease Predicted by Brain Magnetic Resonance Spectroscopy Am J Psychiatry, April 1, 2005; 162(4): 667 - 675. [Abstract] [Full Text] [PDF]
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D. A. Bennett, J. A. Schneider, J. L. Bienias, D. A. Evans, and R. S. Wilson Mild cognitive impairment is related to Alzheimer disease pathology and cerebral infarctions Neurology, March 8, 2005; 64(5): 834 - 841. [Abstract] [Full Text] [PDF]
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M. Muller, A. Aleman, D. E. Grobbee, E. H.F. de Haan, and Y. T. van der Schouw Endogenous sex hormone levels and cognitive function in aging men: Is there an optimal level? Neurology, March 8, 2005; 64(5): 866 - 871. [Abstract] [Full Text] [PDF]
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M. D. Ikonomovic, E. J. Mufson, J. Wuu, D. A. Bennett, and S. T. DeKosky Reduction of Choline Acetyltransferase Activity in Primary Visual Cortex in Mild to Moderate Alzheimer's Disease Arch Neurol, March 1, 2005; 62(3): 425 - 430. [Abstract] [Full Text] [PDF]
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 J. Weuve, J. H. Kang, J. E. Manson, M. M. B. Breteler, J. H. Ware, and F. Grodstein Physical Activity, Including Walking, and Cognitive Function in Older Women JAMA, September 22, 2004; 292(12): 1454 - 1461. [Abstract] [Full Text] [PDF]
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P. M. Horowitz, K. R. Patterson, A. L. Guillozet-Bongaarts, M. R. Reynolds, C. A. Carroll, S. T. Weintraub, D. A. Bennett, V. L. Cryns, R. W. Berry, and L. I. Binder Early N-Terminal Changes and Caspase-6 Cleavage of Tau in Alzheimer's Disease J. Neurosci., September 8, 2004; 24(36): 7895 - 7902. [Abstract] [Full Text] [PDF]
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P. J. Modrego and J. Ferrandez Depression in Patients With Mild Cognitive Impairment Increases the Risk of Developing Dementia of Alzheimer Type: A Prospective Cohort Study Arch Neurol, August 1, 2004; 61(8): 1290 - 1293. [Abstract] [Full Text] [PDF]
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M. Ganguli, H. H. Dodge, C. Shen, and S. T. DeKosky Mild cognitive impairment, amnestic type: An epidemiologic study Neurology, July 13, 2004; 63(1): 115 - 121. [Abstract] [Full Text] [PDF]
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F. C. Bakker, C. J.M. Klijn, J. van der Grond, L. J. Kappelle, and A. Jennekens-Schinkel Cognition and quality of life in patients with carotid artery occlusion: A follow-up study Neurology, June 22, 2004; 62(12): 2230 - 2235. [Abstract] [Full Text] [PDF]
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 R. S. Wilson, C. F. Mendes de Leon, J. L. Bienias, D. A. Evans, and D. A. Bennett Personality and Mortality in Old Age J. Gerontol. B. Psychol. Sci. Soc. Sci., May 1, 2004; 59(3): P110 - P116. [Abstract] [Full Text] [PDF]
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Z. Arvanitakis, R. S. Wilson, J. L. Bienias, D. A. Evans, and D. A. Bennett Diabetes Mellitus and Risk of Alzheimer Disease and Decline in Cognitive Function Arch Neurol, May 1, 2004; 61(5): 661 - 666. [Abstract] [Full Text] [PDF]
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J. A. Schneider, R. S. Wilson, J. L. Bienias, D. A. Evans, and D. A. Bennett Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology Neurology, April 13, 2004; 62(7): 1148 - 1155. [Abstract] [Full Text] [PDF]
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D. A. Bennett, J. A. Schneider, R. S. Wilson, J. L. Bienias, and S. E. Arnold Neurofibrillary Tangles Mediate the Association of Amyloid Load With Clinical Alzheimer Disease and Level of Cognitive Function Arch Neurol, March 1, 2004; 61(3): 378 - 384. [Abstract] [Full Text] [PDF]
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R. S. Wilson, D. A. Evans, J. L. Bienias, C. F. Mendes de Leon, J. A. Schneider, and D. A. Bennett Proneness to psychological distress is associated with risk of Alzheimer's disease Neurology, December 9, 2003; 61(11): 1479 - 1485. [Abstract] [Full Text] [PDF]
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R. S. Wilson, J. L. Bienias, C. F. Mendes de Leon, D. A. Evans, and D. A. Bennett Negative Affect and Mortality in Older Persons Am. J. Epidemiol., November 1, 2003; 158(9): 827 - 835. [Abstract] [Full Text] [PDF]
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R.S. Wilson, J.A. Schneider, J.L. Bienias, S.E. Arnold, D.A. Evans, and D.A. Bennett Depressive symptoms, clinical AD, and cortical plaques and tangles in older persons Neurology, October 28, 2003; 61(8): 1102 - 1107. [Abstract] [Full Text] [PDF]
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C.A. Luis, D.A. Loewenstein, A. Acevedo, W.W. Barker, and R. Duara Mild cognitive impairment: Directions for future research Neurology, August 26, 2003; 61(4): 438 - 444. [Abstract] [Full Text] [PDF]
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E. J. Mufson, M. D. Ikonomovic, S. D. Styren, S. E. Counts, J. Wuu, S. Leurgans, D. A. Bennett, Elizabeth. J. Cochran, and S. T. DeKosky Preservation of Brain Nerve Growth Factor in Mild Cognitive Impairment and Alzheimer Disease Arch Neurol, August 1, 2003; 60(8): 1143 - 1148. [Abstract] [Full Text] [PDF]
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D. A. Bennett, R. S. Wilson, J. A. Schneider, D. A. Evans, C. F. Mendes de Leon, S. E. Arnold, L. L. Barnes, and J. L. Bienias Education modifies the relation of AD pathology to level of cognitive function in older persons Neurology, June 24, 2003; 60(12): 1909 - 1915. [Abstract] [Full Text] [PDF]
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L.L. Barnes, R.S. Wilson, J.A. Schneider, J.L. Bienias, D.A. Evans, and D.A. Bennett Gender, cognitive decline, and risk of AD in older persons Neurology, June 10, 2003; 60(11): 1777 - 1781. [Abstract] [Full Text] [PDF]
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R. S. Wilson, L. A. Beckett, J. L. Bienias, D. A. Evans, and D. A. Bennett Terminal decline in cognitive function Neurology, June 10, 2003; 60(11): 1782 - 1787. [Abstract] [Full Text] [PDF]
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J. Hee Kang and F. Grodstein Regular use of nonsteroidal anti-inflammatory drugs and cognitive function in aging women Neurology, May 27, 2003; 60(10): 1591 - 1597. [Abstract] [Full Text] [PDF]
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