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J Neuropsychiatry Clin Neurosci 13:50-55, February 2001
© 2001 American Psychiatric Press, Inc.

The Psychotic Phenomenon in Probable Alzheimer's Disease

A Positron Emission Tomography Study

Oscar L. Lopez, M.D., Gwenn Smith, Ph.D., James T. Becker, Ph.D., Carolyn Cidis Meltzer, M.D. and Steven T. DeKosky, M.D.

Received September 15, 1999; revised February 7, 2000; accepted March 31, 2000. From the Alzheimer's Disease Research Center and Departments of Neurology, Psychiatry, and Radiology (PET Facility), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Address correspondence to Dr. Lopez, Neuropsychology Research Program, 3501 Forbes Avenue, Suite 830, Pittsburgh, PA 15213.


  ABSTRACT

 
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Positron emission tomography was used to examine the mechanisms of the psychotic phenomenon in Alzheimer's disease (AD). Data from 2 patients with delusions and 2 with hallucinations were compared with those of 5 AD patients without psychosis. The patients with paranoid delusions had diminished relative regional cerebral blood flow (rel-CBF) in the left dorsolateral prefrontal and left medial temporal cortices. The patients with visual hallucinations showed diminished rel-CBF in the right parietal, left medial temporal, and left dorsolateral prefrontal cortices. These findings support the hypothesis that a frontal-temporal abnormality is associated with paranoid delusions in AD. By contrast, visual hallucinations are associated with parietal as well as frontal and temporal lobe dysfunction. In these patients, a left prefrontal–temporal cortex dysfunction appears to be a common denominator for the development of the psychotic phenomenon in AD.

Key Words: Alzheimer's Disease • Psychosis • Delusions • PET Studies

  INTRODUCTION

 
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
P;t4>sychotic symptoms (e.g., delusions, hallucinations) are common in AD patients and impose a considerable burden on caregivers and clinicians involved in the patients' care.1–8 These symptoms are associated with premorbid low educational levels9,10 and are important predictors of institutionalization and cognitive and functional decline in AD patients.11–15 Because the presence of psychotic symptoms can alter the course of the disease and have significant social and medical implications, researchers have explored the clinical, neuropathological, and radiological correlates of delusions, hallucinations, or both in AD patients in order to understand their pathophysiological mechanisms.

One recent approach to the study of cerebral neurophysiology of psychosis in AD has been the use of functional neuroimaging techniques, although the results have been inconsistent (Table 1). Some single-photon emission computed tomography studies in AD patients with delusions have found bilateral temporal lobe hypoperfusion,16 while others found a right temporal17 or frontal18 lobe hypoperfusion. Kotrla et al.19 reported frontal lobe hypoperfusion in patients with delusions and parietal lobe hypoperfusion in those with hallucinations.


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TABLE 1. Functional neuroimaging studies of psychosis in Alzheimer's disease



Positron emission tomography (PET) is a sensitive instrument to measure cerebral metabolism in AD, even in its early stages.20 Grady et al.21 found that patients with psychosis had hypometabolism of the frontal lobes, in addition to temporoparietal dysfunction. Sultzer et al.22 found that delusions, hallucinations, and suspiciousness correlated with frontal hypometabolism. More recently, Hirono et al.23 found that regional cerebral glucose metabolism was increased in the left temporal lobe and decreased in the left occipital lobe in AD patients with a history of delusions.

One of the difficulties with functional neuroimaging studies of psychotic symptoms in AD is that these symptoms rarely occur in isolation. For example, patients with psychosis have more episodes of verbal and physical aggression14,24–26 and more behavioral disturbances14,26 than those without psychosis. The presence of these other psychiatric symptoms can alter the results of neuroimaging studies. Furthermore, patients may present with either delusions or hallucinations (or both), which may have separate clinical and neuroimaging correlates in AD. For example, patients with visual hallucinations may have dysfunction in the right posterior cortex, whereas patients with auditory hallucinations may have greater left posterior cortex dysfunction.

The frontal and temporal lobes appear to be involved in the etiology of both delusions and hallucinations. However, it is not clear whether frontal lobe dysfunction is critical in the etiology of the psychotic phenomenon. It is possible that previous studies detected an abnormality related to the presence of delusions (which are more frequent than hallucinations) but that the functional abnormality associated with hallucinations remains undetected. We report here a series of 4 AD patients with psychosis who underwent PET studies of cerebral blood flow. The purpose of the study was to determine whether there is a critical brain region that serves as a common denominator for the development of the psychotic phenomenon in AD.


  METHODS

 
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
We reviewed the psychiatric characteristics of 9 patients with Probable AD27 who were participating in a longitudinal study of dementia at the University of Pittsburgh. Each patient underwent an extensive evaluation, including medical, neurological, psychiatric, social work/nursing, and neuropsychological examinations, as previously described.5,28 All patients were fluent speakers of English before the onset of dementia. None of these patients had significant signs of cerebrovascular disease, and none met the exclusion criteria of Hachinski Ischemic Score29 greater than 4 or evidence of possible infarction in neuroimaging studies. The clinical diagnosis was reached after a careful review at a consensus conference by two neurologists, two psychiatrists, and two neuropsychologists.

Demographic characteristics of the subjects are shown in Table 2. All patients had more than 12 years of education. Although our goal was to closely match patients by age, educational level, and Mini-Mental State Examination (MMSE) score,30 1 patient with delusions was older and 1 patient with hallucinations was more cognitively impaired than other psychotic and nonpsychotic patients.


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TABLE 2. Demographic and neuropsychiatric characteristics of Alzheimer's disease patients with and without psychosis



First, the relative regional cerebral blood flow (rel-CBF) of the 9 AD patients and 9 nondemented elderly control subjects was examined to determine specific differences between groups. None of the nondemented control subjects had experienced any psychiatric illness or was taking psychiatric medication. Second, the rel-CBF values of 2 patients with delusions and 2 patients with hallucinations were compared and contrasted with the mean rel-CBF of 5 AD patients without those symptoms. All of the 4 patients with psychosis experienced psychotic symptoms within 24 hours of the PET scan session, and none of them was taking psychiatric medication. None of the 5 AD patients without psychosis had experienced symptoms of major depression, mood lability, or apathy, and none of them was taking psychiatric medication.

Psychiatric Assessment
The psychiatric evaluations were conducted by psychiatrists using a semistructured interview.31 Delusions were defined in accordance with the DSM-IV criteria32 and were distinguished from confabulations, disorientation, and amnesia by requiring that the false beliefs be persistent despite evidence to the contrary. Hallucinations were accepted as present if the patient had spontaneously reported a sensory perception with no concomitant external perception. None of these patients had a past history of major depression, a previous psychotic illness, or a history of substance abuse.

Positron Emission Tomography
Subjects were scanned in a Siemens 951R/31 PET scanner. At the end of the transmission scan, 40–50 mCi of [15O]-water was injected as an intravenous bolus, and data acquisition began 30 seconds after the injection. The actual rel-CBF from the [15O]-water time activity data was calculated by using a standard compartment model with corrections for dispersion and timing delays in the blood activity curve.33 The rel-CBF was examined in nine regions of interest (ROIs): orbitofrontal, frontal dorsolateral, anterior cingulate, medial temporal, superior temporal, parietal, and occipital cortices, and basal ganglia and thalami. The rel-CBF data for each ROI were normalized to the whole brain activity by computing an average of all of the ROIs and dividing each ROI by this denominator. The patients' magnetic resonance (MR) scans and a neuroanatomy atlas34 were used to identify the ROI. The MR images were not digitally co-registered to the PET images, but were used to visually guide the identification of the ROI.


  RESULTS

 
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 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Nondemented control subjects showed higher rel-CBF in the left dorsolateral prefrontal cortex, superior temporal, and parietal cortices bilaterally than AD patients. The Mini-Mental State Examination30 and the Mattis Dementia Rating Scale35 scores were higher in nondemented control subjects than in AD patients (Table 3).


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TABLE 3. Relative regional cerebral blood flow in Alzheimer's disease patients and nondemented control subjects



Three principal findings emerged from this study. First, all of the AD patients with psychotic symptoms had significantly lower rel-CBF in the left medial temporal and dorsolateral frontal cortices than AD patients without psychotic symptoms. As shown in Table 4, the rel-CBF values for the psychotic patients in these brains regions were all below the 95% confidence interval established by the nonpsychotic patients. Second, the 2 patients with hallucinations had, in addition, significantly lower rel-CBF in the right parietal cortex relative to the nonpsychotic AD patients. Third, the 2 patients with aggression (1 with hallucinations and 1 with delusions) also had decreased rel-CBF in the right orbital and dorsolateral frontal cortices and the right cingulate cortex.


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TABLE 4. Relative regional cerebral blood flow (rel-CBF) in Alzheimer's disease patients with and without psychosis



One of the patients with delusions had increased rel-CBF in the right thalamus, the other in the left thalamus. One of the patients with hallucinations had increased rel-CBF in the right basal ganglia and right thalamus, the other in the right anterior cingulate gyrus and right orbitofrontal cortex and in the basal ganglia, bilaterally. These results are most likely related to the method of normalizing the data, which accentuated the relatively normal rel-CBF of these regions.


  DISCUSSION

 
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Although most neuroimaging studies have found either a temporal16,17,22 or a frontal18,19 lobe abnormality associated with delusions in AD, our findings suggest that both a frontal and a temporal lobe dysfunction are necessary for the development of psychotic symptoms in general, including delusions. Our findings further suggest that for the development of hallucinations, AD patients must also have an abnormality in the functions of the right parietal cortex.

These findings converge with neuropsychological and neuropathological studies that found temporal and frontal lobe abnormalities in AD patients with psychosis. Neuropsychological studies have shown a greater frontal lobe dysfunction in AD patients with delusions36 and a greater temporal–parietal lobe dysfunction in AD patients with psychosis (e.g., delusions and visual and auditory hallucinations)14 than in AD patients without these features. Neuropathological studies have found more neurofibrillary tangles in the superior middle frontal lobe and more senile (neuritic) plaques in the temporal prosubicular area in AD patients with psychosis than in those without psychosis.37

Aggressive behavior was associated with frontal lobe dysfunction, especially on the right. Because AD patients with aggressive behavior have been shown to have a greater frontal lobe dysfunction than those without aggression,21,38,39 our finding would suggest there is an even greater vulnerability of the frontal association areas in AD patients with both psychosis and aggressive behavior. Moreover, as mentioned above, patients with psychotic symptoms have a higher frequency of aggressive behavior than those without psychosis.14,24–26 These associations may affect neuroimaging studies of psychosis in AD; that is, including a greater number of patients with both aggressive behavior and psychosis may increase the probability of finding hypofrontality associated with psychosis.

Clearly, with a small (albeit well characterized) sample of AD patients with hallucinations and delusions, the current findings are only suggestive. However, the association between parietal and frontal–temporal blood flow reductions in the etiology of delusions or hallucinations is consistent with a variety of behavioral neurological data. The question of whether a combined frontal-temporal system dysfunction is a precondition for the development of the psychotic phenomenon in AD bears careful examination. The results of such a study would have implications not only for the etiology of psychotic phenomena, but also for their possible pharmacological management.


  ACKNOWLEDGMENTS

 
This study was funded by Grants AG03705 and AG05133 from the National Institute on Aging and by Grants MH57078, MH49936, and MH01621 from the National Institute of Mental Health. J.T.B. is a recipient of the Research Scientist Development Award (Level II) (K02-MH01077).


  REFERENCES

 
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Wragg RE, Jeste DV: Overview of depression and psychosis in Alzheimer's disease. Am J Psychiatry 1989; 146:577–587[Abstract/Free Full Text]
  2. Burns A, Jacoby R, Levy R: Psychiatric phenomena in Alzheimer's disease, I: disorders of thought content. Br J Psychiatry 1990; 157:72–76[Abstract/Free Full Text]
  3. Mendez MF, Martin RJ, Smyth KA, et al: Psychiatric symptoms associated with Alzheimer's disease. J Neuropsychiatry Clin Neurosci 1990; 2:28–33[Abstract/Free Full Text]
  4. Drevets WC, Rubin EH: Psychotic symptoms and the longitudinal course of senile dementia of the Alzheimer type. Biol Psychiatry 1989; 25:39–48[CrossRef][Medline]
  5. Becker JT, Boller F, Lopez OL, et al: The natural history of Alzheimer's disease: description of study cohort and accuracy of diagnosis. Arch Neurol 1994; 51:585–594[Abstract/Free Full Text]
  6. Mega MS, Cummings JL, Fiorello T, et al: The spectrum of behavioral changes in Alzheimer's disease. Neurology 1996; 46:130–135[Abstract/Free Full Text]
  7. Levy ML, Cummings JL, Fairbanks LA, et al: Longitudinal assessment of symptoms of depression, agitation, and psychosis in 181 patients with Alzheimer's disease. Am J Psychiatry 1996; 153:1438–1443
  8. Bylsma FW, Folstein MF, Devanand DP, et al: Delusions and patterns of cognitive impairment in Alzheimer's disease. Neuropsychiatry Neuropsychol Behav Neurol 1994; 7:98–103
  9. Flynn FG, Cummings JL, Gornbein J: Delusions in dementia syndromes: investigation of behavioral and neuropsychological correlates. J Neuropsychiatry Clin Neurosci 1991; 3:364–370[Abstract/Free Full Text]
  10. Ortiz H, Lopez OL, Becker JT, et al: Methodological problems in the analysis of delusions and hallucinations in Alzheimer's disease (abstract). Neurology 1997; 48(suppl 3):A99
  11. Lopez OL, Brenner RP, Becker JT, et al: EEG spectral abnormalities and psychosis as predictors of cognitive and functional decline in probable Alzheimer's disease. Neurology 1997; 48:1521– 1525
  12. Stern Y, Albert M, Brandt J, et al: Utility of extrapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission, and death in Alzheimer's disease: prospective analyses from the Predictors Study. Neurology 1994; 44:2300–2307[Abstract/Free Full Text]
  13. Chui HC, Lyness SA, Sobel E, et al: Extrapyramidal signs and psychiatric symptoms predict faster cognitive decline in Alzheimer's disease. Arch Neurol 1994; 51:676–681[Abstract/Free Full Text]
  14. Lopez OL, Becker JT, Brenner RP, et al: Alzheimer's disease with delusions and hallucinations: neuropsychological and electroencephalographic correlates. Neurology 1991; 41:906–912[Abstract/Free Full Text]
  15. Mortimer JA, Ebbitt B, Jun SP, et al: Predictors of cognitive and functional progression in patients with probable Alzheimer's disease. Neurology 1992; 42:1689–1696
  16. Starkstein SE, Vazquez S, Petracca G, et al: A SPECT study of delusions in Alzheimer's disease. Neurology 1994; 44:2055–2059[Abstract/Free Full Text]
  17. Ponton MO, Darcourt J, Miller BL, et al: Psychometric and SPECT studies in Alzheimer's disease with and without delusions. Neuropsychiatry Neuropsychol Behav Neurol 1995; 8:264–270
  18. Staff RT, Shanks MF, Macintosh L, et al: Delusions in Alzheimer's disease: SPECT evidence of right hemisphere dysfunction. Cortex 1999; 35:549–560[Medline]
  19. Kotrla K, Chacko RC, Harper RG, et al: SPECT findings on psychosis in Alzheimer's disease. Am J Psychiatry 1995; 152:1470– 1475
  20. Haxby JV, Grady CL, Duara R, et al: Neocortical metabolic abnormalities precede nonmemory cognitive deficits in early Alzheimer's-type dementia. Arch Neurol 1986; 43:882–885[Abstract/Free Full Text]
  21. Grady CL, Haxby JV, Schapiro MB, et al: Subgroups in dementia of the Alzheimer type identified using positron emission tomography. J Neuropsychiatry Clin Neurosci 1990; 2:373–384[Abstract/Free Full Text]
  22. Sultzer DL, Mahler ME, Mandelkern MA, et al: The relationship between psychiatric symptoms and regional cortical metabolism in Alzheimer's disease. J Neuropsychiatry Clin Neurosci 1995; 7:476–484[Abstract/Free Full Text]
  23. Hirono N, Mori E, Ishii K, et al: Alteration of regional cerebral glucose utilization with delusions in Alzheimer's disease. J Neuropsychiatry Clin Neurosci 1998; 10:433–439[Abstract/Free Full Text]
  24. Deutsch LH, Bylsma FW, Rovner BW, et al: Psychosis and physical aggression in probable Alzheimer's disease. Am J Psychiatry 1991; 148:1159–1163
  25. Aarsland D, Cummings JL, Yenner G, et al: Relationship of aggressive behavior to other neuropsychiatric symptoms in patients with Alzheimer's disease. Am J Psychiatry 1996; 153:243– 247[Abstract/Free Full Text]
  26. Kotrla KJ, Chacko RC, Harper RG, et al: Clinical variables associated with psychosis in Alzheimer's disease. Am J Psychiatry 1995; 152:1377–1379
  27. McKhann G, Drachman DA, Folstein MF, et al: Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's disease. Neurology 1984; 34:939–944[Abstract/Free Full Text]
  28. Lopez OL, Larumbe MR, Becker JT, et al: Reliability of NINDS-AIREN criteria for vascular dementia. Neurology 1994; 44:1240– 1245
  29. Hachinski VC, Iliff LD, Zihka E, et al: Cerebral blood flow in dementia. Arch Neurol 1975; 32:632–637[Abstract/Free Full Text]
  30. Folstein MF, Folstein SE, McHugh PR: "Mini-Mental State:" a practical method grading the cognitive state of patients for the clinician. Psychiatry Res 1975; 12:189–198[CrossRef][Medline]
  31. Mezzich JE, Dow JT, Cottman GA: Developing an information system for a comprehensive psychiatric institute, I: principles, design, and organization. Behav Res Methods Instrument 1981; 13:459–463
  32. American Psychiatric Association: Diagnostic and Statistic Manual of Mental Disorders, 4th edition. Washington, DC, American Psychiatric Association, 1994
  33. Quarles R, Mintun M, Larson K, et al: Measurement of regional cerebral blood flow with positron emission tomography. J Cereb Blood Flow Metab 1994; 13:733–747
  34. Talairach J, Tournoux P: Co-Planar Stereotaxic Atlas of the Human Brain. New York, Thieme Medical, 1988
  35. Mattis S: Mental status examination for organic mental syndrome in the elderly patient, in Geriatric Psychiatry, edited by Bellak L, Karuso TB. New York, Grune and Stratton, 1976
  36. Jeste DV, Wragg RE, Salmon DP, et al: Cognitive deficits of patients with Alzheimer's disease with and without delusions. Am J Psychiatry 1992; 149:184–189[Abstract/Free Full Text]
  37. Zubenko GS, Moossey J, Martinez J: Neuropathologic and neurochemical correlates of psychosis in primary dementia. Arch Neurol 1991; 48:619–624[Abstract/Free Full Text]
  38. Lopez OL, Gonzalez MP, Becker JT, et al: Symptoms of depression and psychosis in frontal lobe dementia and Alzheimer's disease. Neuropsychiatry Neuropsychol Behav Neurol 1996; 9:154–161
  39. Palmer AA, Statman GC, Procter AW, et al: Possible neurotransmitter basis of behavioral changes in Alzheimer's disease. Ann Neurol 1988; 23:616–620[CrossRef][Medline]
  40. Blessed G, Tomlinson BE, Roth M: The association between quantitative measures of dementia and senile changes in the cerebral white matter of elderly subjects. Br J Psychiatry 1968; 114:797–811.40[Abstract/Free Full Text]
  41. Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23:56–62
  42. Hoehn M, Yahr M: Parkinsonism: onset, progression, and mortality. Neurology 1967; 17:427–442[Free Full Text]



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