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The relationship of excess cognitive impairment in MCI and early Alzheimer's disease to the subsequent emergence of psychosis

Published online by Cambridge University Press:  25 September 2008

Elise A. Weamer
Affiliation:
Department of Psychiatry, University of Pittsburgh, Pittsburgh, U.S.A. Department of Neurology, University of Pittsburgh, Pittsburgh, U.S.A.
James E. Emanuel
Affiliation:
Department of Psychiatry, University of Pittsburgh, Pittsburgh, U.S.A.
Daniel Varon
Affiliation:
Department of Psychiatry, University of Pittsburgh, Pittsburgh, U.S.A.
Sachiko Miyahara
Affiliation:
Department of Epidemiology, University of Pittsburgh, Pittsburgh, U.S.A.
Patricia A. Wilkosz
Affiliation:
Department of Psychiatry, University of Pittsburgh, Pittsburgh, U.S.A.
Oscar L. Lopez
Affiliation:
Department of Psychiatry, University of Pittsburgh, Pittsburgh, U.S.A. Department of Neurology, University of Pittsburgh, Pittsburgh, U.S.A.
Steven T. DeKosky
Affiliation:
Department of Psychiatry, University of Pittsburgh, Pittsburgh, U.S.A.
Robert A. Sweet*
Affiliation:
Department of Psychiatry, University of Pittsburgh, Pittsburgh, U.S.A. Department of Neurology, University of Pittsburgh, Pittsburgh, U.S.A. VISN 4 Mental Illness Research, Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA.U.S.A.
*
Correspondence should be addressed to: Robert A. Sweet, M.D., Associate Professor of Psychiatry and Neurology, Biomedical Science Tower, Rm W-1645, 3811 O'Hara Street, Pittsburgh, PA 15213–2593, U.S.A. Phone + 1 412 383 8548; Fax + 1 412 624 9910. Email: sweetra@upmc.edu.

Abstract

Background: Psychotic symptoms in Alzheimer disease (AD + P) identify a heritable phenotype associated with greater cognitive impairment. Knowing when the cognitive course of AD + P subjects diverges from that of subjects without psychosis would enhance understanding of how genetic variation results in AD + P and its associated cognitive burden. This study seeks to determine whether the degree of cognitive impairment and cognitive decline in early AD predicts subsequent AD + P onset.

Methods: 361 subjects with possible or probable AD or mild cognitive impairment (MCI) without psychosis were evaluated every 6 months until psychosis onset.

Results: Severity of cognitive dysfunction was a strong predictor of AD + P up to two years prior to psychosis onset. Cognition did not decline more rapidly prior to onset of AD + P.

Conclusions: Individuals who will develop AD + P already demonstrate excess cognitive impairment during the mild stages of disease. Genetic variation and brain pathophysiology may lead to a cognitive risk phenotype which is present prior to dementia onset.

Type
Research Article
Copyright
Copyright © International Psychogeriatric Association 2008

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References

Bacanu, S. A., Devlin, B., Chowdari, K. V., DeKosky, S. T., Nimgaonkar, V. L. and Sweet, R. A. (2002). Linkage analysis of Alzheimer disease with psychosis. Neurology, 59, 118120.CrossRefGoogle ScholarPubMed
Ballard, C. G., O'Brien, J. T., Coope, B. and Wilcock, G. (1997). Psychotic symptoms in dementia and the rate of cognitive decline. Journal of the American Geriatrics Society, 45, 10311032.CrossRefGoogle ScholarPubMed
Becker, J. T., Boller, F., Saxton, J. and McGonigle-Gibson, K. L. (1987). Normal rates of forgetting of verbal and non-verbal material in Alzheimer's disease. Cortex, 23, 5972.Google Scholar
Becker, J. T., Boller, F., Lopez, O. L., Saxton, J. and McGonigle, K. L. (1994). The natural history of Alzheimer's disease: description of study cohort and accuracy of diagnosis. Archives of Neurology, 51, 585594.Google Scholar
Benton, A. L. (1968). Differential behavioral effects in frontal lobe disease. Neuropsychologia, 6, 5360.Google Scholar
Benton, A. L., Hamsher, K., Varney, N. R. and Spreen, O. (1983). Contribution to Neuropsychological Assessment: A Clinical Manual. New York: Oxford University Press.Google Scholar
Borkowski, J. G., Benton, A. L. and Spreen, O. (1967). Word fluency and brain damage. Neuropsychologia, 5, 135140.Google Scholar
Davies, C. A., Mann, D. M., Sumpter, P. Q. and Yates, P. O. (1987). A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer's disease. Journal of the Neurological Sciences, 78, 151164.CrossRefGoogle ScholarPubMed
DeKosky, S. T. and Scheff, S. W. (1990). Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Annals of Neurology, 27, 457464.Google Scholar
Drevets, W. C. and Rubin, E. H. (1989). Psychotic symptoms and the longitudinal course of senile dementia of the Alzheimer type. Biological Psychiatry, 25, 3948.Google Scholar
Folstein, M. F., Folstein, S. E. and McHugh, P. R. (1975). “Mini mental state”: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189198.Google Scholar
Glantz, L. A. and Lewis, D. A. (2000). Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Archives of General Psychiatry, 57, 6573.Google Scholar
Guenette, S. Y. and Tanzi, R. E. (1999). Progress toward valid transgenic mouse models for Alzheimer's disease. Neurobiology of Aging, 20, 201211.Google Scholar
Hollingworth, P. et al. (2007). Increased familial risk and genomewide significant linkage for Alzheimer's disease with psychosis. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 144B, 841848.CrossRefGoogle ScholarPubMed
Hsia, A. Y. et al. (1999). Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proceedings of the National Academy of Sciences U.S.A, 96, 32283233.Google Scholar
Jeste, D. V., Wragg, R. E., Salmon, D. P., Harris, M. J. and Thal, L. J. (1992). Cognitive deficits of patients with Alzheimer's disease with and without delusions. American Journal of Psychiatry, 149, 184189.Google Scholar
Kaplan, E. F., Goodglass, H. and Weintraub, S. (1983). The Boston Naming Test. Philadelphia: Lea & Febiger.Google Scholar
Levy, M. L., Cummings, J., Fairbanks, L. A., Bravi, D., Calvani, M. and Carta, A. (1996). Longitudinal assessment of symptoms of depression, agitation, and psychosis in 181 patients with Alzheimer's disease. American Journal of Psychiatry, 153, 14381443.Google Scholar
Lopez, O. L., Kamboh, M. I., Becker, J. T., Kaufer, D. I. and DeKosky, S. T. (1997). The apolipoprotein E ɛ4 allele is not associated with psychiatric symptoms or extrapyramidal signs in probable Alzheimer's disease. Neurology, 49, 794797.CrossRefGoogle ScholarPubMed
Lopez, O. L., Wisniewski, S. R., Becker, J. T., Boller, F. and DeKosky, S. T. (1999). Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease. Archives of Neurology, 56, 12661272.Google Scholar
Lopez, O. L. et al. (2000)a. Research evaluation and diagnosis of probable Alzheimer's disease over the last two decades. I. Neurology, 55, 18541862.Google Scholar
Lopez, O. L. et al. (2000)b. Research evaluation and diagnosis of possible Alzheimer's disease over the last two decades. II. Neurology, 55, 18631869.Google Scholar
Lopez, O. L. et al. (2003). Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. Archives of Neurology, 60, 13851389.Google Scholar
Masliah, E. et al. (2001). Altered expression of synaptic proteins occurs early during progression of Alzheimer's disease. Neurology, 56, 127129.Google Scholar
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E. M. (1984). 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. Neurology, 34, 939944.CrossRefGoogle ScholarPubMed
Niendam, T. A. et al. (2003). A prospective study of childhood neurocognitive functioning in schizophrenic patients and their siblings. American Journal of Psychiatry, 160, 20602062.Google Scholar
Paulsen, J. S. et al. (2000)a. Neurobehaviors and psychotic symptoms in Alzheimer's disease. Journal of the International Neuropsychological Society, 6, 815820.Google Scholar
Paulsen, J. S. et al. (2000)b. Incidence of and risk factors for hallucinations and delusions in patients with probable Alzheimer's disease. Neurology, 54, 19651971.CrossRefGoogle Scholar
Reitan, R. M. and Wolfson, D. (1993). The Halstead-Reitan Neuropsychological Test Battery. Tuson: Neuropsychology Press.Google Scholar
Rockwell, E., Jackson, E., Vilke, G. and Jeste, D. V. (1994). A study of delusions in a large cohort of Alzheimer's disease patients. American Journal of Geriatric Psychiatry, 2, 157164.Google Scholar
Rosen, W. G., Mohs, R. C. and Davis, K. L. (1984). A new rating scale for Alzheimer's disease. American Journal of Psychiatry, 141, 13561364.Google Scholar
Saxton, J. et al. (2004). Preclinical Alzheimer disease: neuropsychological test performance 1.5 to 8 years prior to onset. Neurology, 63, 23412347.Google Scholar
Scarmeas, N. et al. (2005). Delusions and hallucinations are associated with worse outcome in Alzheimer disease. Archives of Neurology, 62, 16011608.Google Scholar
Scheff, S. W. and Price, D. A. (2003). Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies. Neurobiology of Aging, 24, 10291046.Google Scholar
Snitz, B. E., Macdonald, A. W. III and Carter, C. S. (2006). Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. Schizophrenia Bulletin, 32, 179194.Google Scholar
Snowdon, D. A., Kemper, S. J., Mortimer, J. A., Greiner, L. H., Wekstein, D. R. and Markesbery, W. R. (1996). Linguistic ability in early life and cognitive function and Alzheimer's disease in late life – findings from the Nun Study. JAMA, 275, 528532.CrossRefGoogle ScholarPubMed
Stern, Y., Mayeux, R., Sano, M., Hauser, W. A. and Bush, T. (1987). Predictors of disease course in patients with probable Alzheimer's disease. Neurology, 37, 16491653.Google Scholar
Sweet, R. A., Nimgaonkar, V. L., Kamboh, M. I., Lopez, O. L., Zhang, F. and DeKosky, S. T. (1998). Dopamine receptor genetic variation, psychosis, and aggression in Alzheimer's disease. Archives of Neurology, 55, 13351340.Google Scholar
Sweet, R. A., Nimgaonkar, V. L., Devlin, B., Lopez, O. L. and DeKosky, S. T. (2002)a. Increased familial risk of the psychotic phenotype of Alzheimer disease. Neurology, 58, 907911.Google Scholar
Sweet, R. A. et al. (2002)b. Psychosis in Alzheimer disease: postmortem magnetic resonance spectroscopy evidence of excess neuronal and membrane phospholipid pathology. Neurobiology of Aging, 23, 547553.Google Scholar
Sweet, R. A. et al. (2005). Catechol-O-methyltransferase haplotypes are associated with psychosis in Alzheimer disease. Molecular Psychiatry, 10, 10261036.Google Scholar
Sweet, R. A., Bergen, S. E., Sun, Z., Marcsisin, M. J., Sampson, A. R. and Lewis, D. A. (2007). Anatomical evidence of impaired feedforward auditory processing in schizophrenia. Biological Psychiatry, 61, 854864.Google Scholar
Tariot, P. N. et al. and Behavioral Pathology Committee of the Consortium to Establish a Registry for Alzheimer's Disease (1995). The behavior rating scale for dementia of the Consortium to Establish a Registry for Alzheimer's Disease. American Journal of Psychiatry, 152, 13491357.Google Scholar
Wechsler, D. (1987). The Wechsler Memory Scale Manual-Revised. New York: The Psychological Corporation.Google Scholar
Whalley, L. J., Starr, J. M., Athawes, R., Hunter, D., Pattie, A. and Deary, I. J. (2000). Childhood mental ability and dementia. Neurology, 55, 14551459.Google Scholar
Wilkosz, P. A., Miyahara, S., Lopez, O. L., DeKosky, S. T. and Sweet, R. A. (2006). Prediction of psychosis onset in Alzheimer disease: the role of cognitive impairment, depressive symptoms, and further evidence for psychosis subtypes. American Journal of Geriatric Psychiatry, 14, 352356.Google Scholar