Cognitive Impairment in Early, Untreated Parkinson's Disease and Its Relationship to Motor Disability

Abstract

Current knowledge of cognitive dysfunction in Parkinson's disease (PD) has largely been obtained from studies of chronically treated patients in whom effects of disease chronicity, treatment, depression and dementia are confounding factors. Studies of untreated patients have examined few cognitive domains and relationships between cognition, depression and motor disability have been incompletely explored. Accordingly, we studied 60 consecutive patients with newly diagnosed, untreated, idiopathic PD and 37 matched, healthy control subjects; no subject had clinical dementia or depression. All subjects received tests of specific processes of memory and cognition, including working memory, verbal and non-verbal short- and long-term memory, language, visuospatial capacity, set-formation and shifting and sequencing. Patients also received quantitative global clinical measures of severity of dementia, depression and motor disability. The PD group as a whole showed deficits in immediate recall of verbal material, language production and semantic fluency, set-formation, cognitive sequencing and working memory and visuomotor construction. However, this group was unimpaired in immediate memory span, long-term forgetting, naming, comprehension and visual perception. Language deficits and more severe frontal lobe impairments were confined to those PD patients scoring abnormally on a Mini Mental State examination. Motor disability correlated strongly with severity of depression but weakly with cognitive impairment. Cognitive sequencing, set-formation and set-shifting deficits tended to associate with depression, but otherwise there was no association between cognition and depression. The results indicate dissociation of cognition and motor control in early PD which suggests that cognitive dysfunction is largely independent of frontostriatal dopamine deficiency underlying motor disability. Some, but not all, of the frontal lobe deficits of chronic disease are detectable in early, untreated PD. The pathogenesis of the cognitive deficits shown here appears to involve extrastriatal dopamine systems or non-dopaminergic pathology. Longitudinal study is necessary to determine whether increasing disease duration exacerbates the early cognitive deficits and affects new cognitive domains, in addition to producing increasing motor disability.

The anatomy of melancholia: does frontal-subcortical pathophysiology underpin its psychomotor and cognitive manifestations?

“…While there is little correlation between motor disability and cognitive impairment in PD (Cooper et al 1991), cognitive deficits tend to be associated with concurrent depression. For example, Starkstein et al (1989), in a matched control study examining cognitive impairment in PD patients with and without depression, found that the depressed PD patients performed significantly worse than the non-depressed PD subjects on all aspects of neuropsychological function, but especially frontal tasks.…”

Gait dynamics, fractals and falls: Finding meaning in the stride-to-stride fluctuations of human walking

“…Thus, these findings support the idea that reduced stride-to-stride variability on the treadmill and the increased stride-to-stride variability typically seen in PD seems likely to be a result of changes in locomotor rhythmicity. (Cooper, Sagar, Jordan, Harvey, & Sullivan, 1991;Elias & Treland, 1999;Hausdorff et al, 2006;Yogev et al, 2005) and the putative reliance of a steady gait on this cognitive domain, we hypothesized that MPH may improve gait and reduce fall risk in patients with PD. MPH has a long history as the drug of choice for improving attention in children with ADHD, however, its potential to modify motor function is less known.…”

Cognitive and Behavioural Changes After Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease

“…Among the cognitive deficits which may be detected in patients with Parkinson's disease, deficits of executive functions (planning, problem solving, set-shifting), mediated by disruption of neural circuits involving the frontal lobes and the basal ganglia, are the most common in both early disease phases and in patients with advanced Parkinson's disease Cooper et al, 1991;Robbins et al, 1994;Taylor et al, 1986;Cools et al, 2001;Green et al, 2002). (Boller et al, 1984;Hovestadt et al, 1987;Ransmayr et al, 1987), impairment on language tasks of verbal fluency (Matison et al, 1982;Cooper et al, 1991) and tasks of oral naming (Peran et al, 2003) may occur in individual Parkinsonian patients since early phases and become more frequent in advanced Parkinson's disease (Green et al, 2002).…”

“…(Boller et al, 1984;Hovestadt et al, 1987;Ransmayr et al, 1987), impairment on language tasks of verbal fluency (Matison et al, 1982;Cooper et al, 1991) and tasks of oral naming (Peran et al, 2003) may occur in individual Parkinsonian patients since early phases and become more frequent in advanced Parkinson's disease (Green et al, 2002).…”

“…As to memory deficits, different studies reported in Parkinsonian patients an impairment of episodic memory (Taylor et al, 1986), verbal short-term memory (Cooper et al, 1991), spatial short-term memory (Robbins et al, 1994), and procedural memory (Harrington et al, 1990). In patients with Parkinson's disease and dementia, the pattern of neuropsychological impairment may differ in distinct patient subgroups.…”