Skip to main content
    • Aa
    • Aa

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

  • Elise A. Weamer (a1) (a2), James E. Emanuel (a1), Daniel Varon (a1), Sachiko Miyahara (a3), Patricia A. Wilkosz (a1), Oscar L. Lopez (a1) (a2), Steven T. DeKosky (a1) and Robert A. Sweet (a1) (a2) (a4)...

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.

Corresponding author
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:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

C. G. Ballard , J. T. O'Brien , B. Coope and G. Wilcock (1997). Psychotic symptoms in dementia and the rate of cognitive decline. Journal of the American Geriatrics Society, 45, 10311032.

J. T. Becker , F. Boller , J. Saxton and K. L. McGonigle-Gibson (1987). Normal rates of forgetting of verbal and non-verbal material in Alzheimer's disease. Cortex, 23, 5972.

A. L. Benton (1968). Differential behavioral effects in frontal lobe disease. Neuropsychologia, 6, 5360.

J. G. Borkowski , A. L. Benton and O. Spreen (1967). Word fluency and brain damage. Neuropsychologia, 5, 135140.

S. T. DeKosky and S. W. Scheff (1990). Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Annals of Neurology, 27, 457464.

M. F. Folstein , S. E. Folstein and P. R. McHugh (1975). “Mini mental state”: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189198.

L. A. Glantz and D. A. Lewis (2000). Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Archives of General Psychiatry, 57, 6573.

S. Y. Guenette and R. E. Tanzi (1999). Progress toward valid transgenic mouse models for Alzheimer's disease. Neurobiology of Aging, 20, 201211.

P. Hollingworth (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.

O. L. Lopez , M. I. Kamboh , J. T. Becker , D. I. Kaufer and S. T. DeKosky (1997). The apolipoprotein E ɛ4 allele is not associated with psychiatric symptoms or extrapyramidal signs in probable Alzheimer's disease. Neurology, 49, 794797.

O. L. Lopez , S. R. Wisniewski , J. T. Becker , F. Boller and S. T. DeKosky (1999). Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease. Archives of Neurology, 56, 12661272.

O. L. Lopez (2003). Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1. Archives of Neurology, 60, 13851389.

G. McKhann , D. Drachman , M. Folstein , R. Katzman , D. Price and E. M. Stadlan (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.

T. A. Niendam (2003). A prospective study of childhood neurocognitive functioning in schizophrenic patients and their siblings. American Journal of Psychiatry, 160, 20602062.

J. S. Paulsen (2000)a. Neurobehaviors and psychotic symptoms in Alzheimer's disease. Journal of the International Neuropsychological Society, 6, 815820.

J. Saxton (2004). Preclinical Alzheimer disease: neuropsychological test performance 1.5 to 8 years prior to onset. Neurology, 63, 23412347.

N. Scarmeas (2005). Delusions and hallucinations are associated with worse outcome in Alzheimer disease. Archives of Neurology, 62, 16011608.

S. W. Scheff and D. A. Price (2003). Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies. Neurobiology of Aging, 24, 10291046.

B. E. Snitz , A. W. III Macdonald and C. S. Carter (2006). Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. Schizophrenia Bulletin, 32, 179194.

D. A. Snowdon , S. J. Kemper , J. A. Mortimer , L. H. Greiner , D. R. Wekstein and W. R. Markesbery (1996). Linguistic ability in early life and cognitive function and Alzheimer's disease in late life – findings from the Nun Study. JAMA, 275, 528532.

Y. Stern , R. Mayeux , M. Sano , W. A. Hauser and T. Bush (1987). Predictors of disease course in patients with probable Alzheimer's disease. Neurology, 37, 16491653.

R. A. Sweet , V. L. Nimgaonkar , B. Devlin , O. L. Lopez and S. T. DeKosky (2002)a. Increased familial risk of the psychotic phenotype of Alzheimer disease. Neurology, 58, 907911.

R. A. Sweet (2005). Catechol-O-methyltransferase haplotypes are associated with psychosis in Alzheimer disease. Molecular Psychiatry, 10, 10261036.

R. A. Sweet , S. E. Bergen , Z. Sun , M. J. Marcsisin , A. R. Sampson and D. A. Lewis (2007). Anatomical evidence of impaired feedforward auditory processing in schizophrenia. Biological Psychiatry, 61, 854864.

P. A. Wilkosz , S. Miyahara , O. L. Lopez , S. T. DeKosky and R. A. Sweet (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.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

International Psychogeriatrics
  • ISSN: 1041-6102
  • EISSN: 1741-203X
  • URL: /core/journals/international-psychogeriatrics
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 2
Total number of PDF views: 3 *
Loading metrics...

Abstract views

Total abstract views: 71 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 29th May 2017. This data will be updated every 24 hours.