Extrapyramidal Motor Abnormalities Associated With Late-life Psychosis

Extrapyramidal Motor Abnormalities Associated With Late-Life Psychosis by Michael P. Caligiuri, James B. Lohr, Diane Panton, and M. Jackuelyn Harris Abstract Studies of extrapyramidal motor function in patients with schizophrenia have contributed to our understanding of the phenomenology and therapeutic outcome associated with neuroleptics. An increasing body of literature suggests that extrapyramidal motor abnormalities associated with schizophrenia may be linked to the pathophysiological mechanisms responsible for schizophrenia. Similarly, it has been documented that the extrapyramidal system may be involved in motor abnormalities in patients with Alzheimer's disease (AD). The present study was undertaken to examine motor function in schizophrenia and AD patients with psychosis. Quantitative instrumental procedures were used to examine rigidity, tremor, and bradykinesia in 13 neuroleptic-naive patients with schizophrenia, 13 AD patients with psychosis, and 26 agecomparable controls. Both schizophrenia and AD patients had significantly higher tremor and rigidity scores than did normal subjects. This comparative study of schizophrenia and AD patients with psychosis suggests that the effect of dementia in patients with psychosis is to prolong movement time, whereas abnormal parkinsonian postural tremor tends to be associated with psychosis in the absence of dementia. Previous studies of motor function in neuropsychiatric patients have contributed to our understanding of the phenomenology and therapeutic outcome associated with neuroleptics. There is evidence from studies of neuroleptic-naive patients suggesting that parkinsonian motor disturbances may be directly related to schizophrenia. Extrapyramidal disorders such as tremor, rigidity, and akinesia were observed in many of the patients described by Kraepelin (1919/1921) in his treatise on dementia praecox. Subsequent clinical (Reiter 1926; Mettler and Crandell 1959a, 1959b) and laboratory (Caligiuri et al. 1993) investigations have found that a sizable proportion of drugfree schizophrenia patients exhibited parkinsonism. The presence of extrapyramidal involvement in patients with Alzheimer disease (AD) is well established (Mayeux et al. 1985; Ditter and Mirra 1987; Hansen et al. 1990; Tyrell et al. 1990). It remains unclear, however, whether the extrapyramidal motor disturbances found in AD are similar to those found in schizophrenia. The presence of extrapyramidal motor signs in schizophrenia and AD patients suggests abnormal nigrostriatal dopaminergic neurotransmission. Anatomic and physiologic evidence implicating this region of the basal ganglia in schizophrenia comes from functional imaging studies (Owen et al. 1978; Wong et al. 1986) and postmortem neurochemical studies (Bird et al. 1979, 1984; Seeman et al. 1984; Bracha and Kleinman 1986). Neuropathological studies of AD have implicated the substantia nigra and substantia innominata as the subcortical sites involved in producing extrapyramidal motor Reprint requests should be sent to Dr. M.P. Caligiuri, Motor Function Laboratory (V-116), VA Medical Center, 3350 La Jolla Village Dr., San Diego, CA 92161. VOL. 19, NO. 4, 1993 SCHIZOPHRENIA BULLETIN 748 Methods Subjects. Fifty-two subjects were studied; 26 were patients with psychosis that began during late life (after age 45) and 26 were age-matched normal comparison (NC) subjects. The patients either had no past exposure to neuroleptic medication or had been neuroleptic-free for at least 10 years. Psychiatric diagnoses were made according to DSM-III-R criteria (American Psychiatric Association 1987) by board-certified staff psychiatrists (M.J.H. and D.P.). Thirteen patients were diagnosed as having either schizophrenia or delusional disorders, and 13 patients were diagnosed as having probable AD. All patients were candidates for neuroleptic treatment and were examined before beginning treatment. All AD patients exhibited at least mild psychosis as judged by clinical assessment (see below). The mean age of the schizophrenia patients was 60.7 (standard deviation [SD] = 8.8) years; that of the AD patients was 77.7 (±10.5) years. Because schizophrenia patients were significantly younger than AD patients (t = 4.28, p < 0.01), normative data from an ongoing data base were selected to attain age comparability for the two groups. NC subjects had been recruited over the previous 4 years from among San Diego Department of Veterans Affairs Medical Center volunteers, staff, patients' spouses, and conservators. All NC subjects were over the age of 45 years. Data from some of the NC subjects and schizophrenia patients have been reported previously in studies validating the quantitative procedures (Caligiuri et al. 1993; Caligiuri and Galasko 1992). Procedures. All subjects underwent laboratory assessment for parkinsonism. Patients received the Brief Psychiatric Rating Scale (BPRS; Overall and Gorham 1962) to rate the overall severity of psychopathology and the positive and negative symptom severity on the basis of subscale scores (Jeste et al. 1984; McGlashan and Fenton 1992). Positive symptoms included disorganized speech, suspiciousness, hallucinatory behavior, hallucinatory statements, and unusual thought content. Negative symptoms included emotional withdrawal, motor retardation, and blunted affect. Group characteristics and mean BPRS scores for the three groups are shown in table 1. Group comparisons for the total and for positive and negative subscale scores revealed no significant differences. Parkinsonism was examined with an established instrumental procedure for quantifying rigidity, postural tremor, and aspects of bradykinesia. Quantitative motor assessment offers the advantage of sensitivity to mild abnormalities. With these laboratory procedures, relatively mild parkinsonian signs, which would remain undetected by an observer, can be identified on the basis of statistical criteria. Electromechanical devices have been shown to be sensitive to mild rigidity and parkinsonian tremor, making them particularly useful in studies of psychopathology and aging. Hand rigidity was quantified by means of a device that transduces displacement and force simultaneously (Caligiuri and Galasko 1992). Stiffness slope coefficients were obtained from resting and activated conditions. The ratio of the activated coefficient to the resting coefficient was used as the index to score severity of parkinsonian rigidity. Postural tremor was quantified using a hand force transducer. We have previously demonstrated that sustained force is a sensitive procedure for quantifying postural tremor phenomena signs (Hansen et al. 1990), whereas functional imaging studies showed abnormal activity within the putamen and caudate (Tyrell et al. 1990) and ventricular enlargement (Burns et al. 1991) in AD patients with parkinsonism. The neuropathological and neurochemical similarities between AD and schizophrenia patients with extrapyrami (...truncated)