Elsevier

Brain and Cognition

Volume 50, Issue 2, November 2002, Pages 194-206
Brain and Cognition

Patterns of neuropsychological performance in multiple system atrophy compared to sporadic and hereditary olivopontocerebellar atrophy

https://doi.org/10.1016/S0278-2626(02)00503-1Get rights and content

Abstract

Although neuropsychological symptoms are associated with multiple system atrophy (MSA), sporadic olivopontocerebellar atrophy (sOPCA), and dominantly inherited olivopontocerebellar atrophy (dOPCA), the differences between these groups have not been explored. We compared 28 MSA patients on psychiatric rating scales and neuropsychological measures to 67 sOPCA patients, 42 dOPCA patients, and 30 normal controls. Patients with dOPCA, sOPCA, and MSA all exhibited significant deficits on motor-related tasks, as well as relatively mild deficits in cognitive functioning. Patients with MSA had greater neuropsychological dysfunction, particularly in memory and other “higher order” cognitive processes, than patients with either sOPCA or dOPCA.

Introduction

Multiple system atrophy (MSA) is a progressive neurodegenerative disease that includes varying combinations of parkinsonian features, cerebellar disorders, pyramidal tract dysfunction, and autonomic insufficiency (Gilman et al., 1998; Wenning, Ben-Shlomo, Magalhaes, Daniel, & Quinn, 1994). Levodopa therapy often results in limited or no reduction in the parkinsonian features (Izumi, Inoue, Shirabe, Miyazaki, & Kuroiwa, 1971; Ito, Kusaka, Matsumoto, & Imai, 1996; Rajput, Kazi, & Rozdilsky, 1972; Wenning et al., 1994). The neuropathological changes include neuronal loss, gliosis, and both oligodendroglial and neuronal intracytoplasmic and intranuclear argyrophilic inclusions in the basal ganglia, brainstem, cerebellum, and spinal cord (Kume, Takahashi, Hashizume, & Asai, 1991; Lantos & Papp, 1994; Oppenheimer, 1984; Wenning et al., 1994). The prevalence of MSA has been estimated to be approximately 4.4 per 100,000 population (Schrag, Ben-Shlomo, & Quinn, 1999), with cases reported worldwide.

Olivopontocerebellar atrophy (OPCA) is a related neurodegenerative disorder characterized by progressive cerebellar ataxia due to neuronal loss in the inferior olives, pons, and cerebellar cortex (Eadie, 1975a, Eadie, 1975b; Gilman, Bloedel, & Lechtenberg, 1981; Harding, 1984; Oppenheimer, 1984). Cases of OPCA occur as a sporadic (sOPCA) or hereditary disorder, usually with dominant transmission (dOPCA). Now that identification of the mutation responsible for dOPCA in some families has become available, these patients are subclassified as SCA (spinocerebellar ataxia) types 1–17. Both sOPCA and dOPCA lead to atrophy of the cerebellum and brainstem (Gilman et al., 1988), and the decreased tissue mass results in decreased local blood flow in the cerebellum (Gilman et al., 1995), and decreased glucose metabolic rates in the cerebellum and brainstem (Gilman et al., 1995). Some and perhaps most patients with sOPCA evolve to develop MSA (Gilman et al., 2000). The prevalence of olivopontocerebellar atrophy has been estimated to be around 2 in 100,000 (Berciano, 1993), and cases have been reported worldwide.

Little information is available to indicate whether MSA patients have neuropsychological findings or patterns that differentiate them from dOPCA and sOPCA patients. Moreover, the reported presence and nature of neuropsychological deficits associated with OPCA have been variable. Estimates of the incidence of dementia in OPCA have varied widely, from as high as 80% (Jellinger & Tarnowska-Dziduozko, 1971) to as low as 11% (Berciano, 1982). In addition, Kish and colleagues (Kish et al., 1988, Kish et al., 1994) reported generalized but relatively mild cognitive deficits in dOPCA, particularly frontal lobe dysfunction (El-Awar et al., 1991; Botez-Marquard & Botez, 1993). Frontal lobe dysfunction has been reported also in MSA (Robbins et al., 1992).

We previously reported that motor dysfunction appeared to account for an initial discrepancy on cognitive tasks between OPCA patients and normal controls (Berent et al., 1996), noting that there were no significant between group differences in cognitive performance when we controlled for educational level and impairments in motor function (Berent et al., 1990). Moreover, patients with OPCA displayed a variety of relatively intact and average cognitive abilities (Berent et al., 1996, Berent et al., 1990).

Emotional disturbances have been implicated in OPCA. We previously reported high levels of depression and anxiety in OPCA patients, as compared to normal controls (Berent et al., 1996). Although the OPCA patients in our earlier work evidenced higher levels of depression than normal, with some individual self-ratings as high as those seen in formally diagnosed psychiatric patients, the overall level of severity remained relatively mild (Berent et al., 1996). We also found a strongly positive relationship between ratings of emotional disturbance and glucose metabolic rates in the frontal lobes in both sOPCA and dOPCA (Berent et al., 1990). Little research has been conducted on psychiatric disturbances in MSA, although one recent study reported that a sample of 12 patients with striatonigral-type MSA was characterized by blunted affect, with one patient reporting symptoms consistent with major depression and one patient reporting symptoms consistent with dysthymia (Fetoni, Soliveri, Monza, Testa, & Girotti, 1999).

Although neuropsychological symptoms are associated with MSA, sOPCA, and dOPCA, the differences between these three groups have not been explored. It is unknown whether specific neuropsychological findings or patterns may be unique to each diagnostic group. In a study of cerebral glucose metabolism utilizing positron emission tomography, distinctive regional patterns of decreased metabolism are found in patients with dOPCA, sOPCA, and MSA, with more similarity between sOPCA and MSA, than between dOPCA and either MSA or sOPCA (Gilman et al., 1994). Moreover, sOPCA patients tended to perform more poorly than dOPCA patients on some cognitive tasks, particularly on measures of initial learning for verbal and visual stimuli (Berent et al., 1996).

The present study was undertaken to examine the neuropsychological functioning in MSA patients as compared with sOPCA patients, dOPCA patients, and normal controls. Based on previous studies and the widespread neuropathological findings, we hypothesized that MSA patients would show more extensive neuropsychological dysfunction, including involvement of memory and other “higher order” cognitive functions, reflecting the multiple systems involved in the disease, than patients with either sOPCA or dOPCA. As mentioned earlier, there is some indication that disturbances in motor and emotional functioning may represent confounding factors and could adversely impact on cognitive performance in patients with OPCA or MSA. Therefore, it is important to consider such factors in research with these patient populations.

Section snippets

Patient groups and normal controls

This study was approved by the Institutional Human Use Review Board of the University of Michigan and informed consent was obtained from each subject after the nature of the procedure had been fully explained. Over a three year interval all subjects seen through the Neuropsychology service who had a diagnosis of MSA, sOPCA, or dOPCA, and who agreed to participate were included. Based upon history, clinical examination, laboratory findings, and imaging studies, patients were grouped according to

General

Participants consisted of 76 (46%) men and 91 (54%) women with a mean age of 54 years and a mean of 14 years of education (Table 1). Descriptive statistics for neuropsychological variables are presented in Table 2 and measures of emotional functioning in Table 3. Dysarthria severity rating, assigned by the speech pathologist, ranged from one (mild) to three (severe). According to these clinical ratings, MSA patients were significantly more dysarthric than sOPCA or dOPCA patients (F[2,129]=7.17,

Discussion

In this study, patients with dOPCA, sOPCA, and MSA all exhibited deficits on motor-related tasks, whereas, specific difficulties on tasks of learning and recognition memory may better differentiate between these patient groups. These results generally support the notion that patients with MSA have greater neuropsychological dysfunction, particularly in memory and other “higher order” cognitive processes (as seen in performance on tasks of learning, recognition memory, and verbal fluency), than

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    This study is supported in part by grants from the National Institutes of Health (NS 15655, AG 08671 and AG 07378).

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