One hundred de novo patients with Parkinson's disease (PD) were classified into two groups according to age of onset of symptoms. Seventy two patients were under 70 years and 28 were 70 years and over. All patients were given neurological and neuropsychological assessments, and the severity of the signs was rated on a modified Columbia scale. The neuropsychological assessment was also administered to 50 age-and-education-matched controls. The neuropsychological test battery included tests of verbal learning, visual memory, verbal fluency, visuospatial skill, simple and choice reaction time, language and maze learning. The late-onset patients had significant impairment in nonverbal reasoning, auditory verbal learning, visual memory and choice reaction time in contrast to early-onset patients and controls. A relationship was found between bradykinesia and widespread cognitive impairment. Severity of tremor was found to be significantly correlated with impairment in auditory verbal learning, visual memory and increased choice reaction time, while rigidity was found to be associated with cognitive impairment in verbal fluency and visuospatial skill. Using DSM II criteria, 39% of the late-onset and 8% of the early-onset group were classified as demented. Dementia was more common in patients with bilateral symmetrical disease and in those patients with marked tremor and bradykinesia. The pattern of cognitive impairment in PD was consistent with that associated with a subcortical dementia. This study confirms that the expression of PD is markedly influenced by the age of onset.

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The study was designed to examine the effects of long-term anticholinergic therapy on neuropsychological functioning in a group of non-demented PD patients before and after treatment with benzhexol. Forty-two de novo patients with PD who were participants in a larger multicentre drug study were divided into two groups according to long treatment with and without an anticholinergic agent. There were 12 in the anticholinergic group. All patients were receiving treatment with either levodopa or bromocriptine or a combination of the two as their primary therapy. The patients were given a detailed neuropsychological assessment at baseline before commencing treatment. The assessment was repeated in phase 2 after 3 years of treatment. The groups were compared at baseline and at 3 years. Those patients treated with anticholinergics had significant impairment in their performance in an auditory verbal learning test compared to those treated with dopaminergic therapy alone. By contrast, their speed of retrieval of words from memory in a verbal fluency test significantly improved. Analysis of the serial position curve revealed that the anticholinergic group had impairment in the recency effect (short-term memory store). It is suggested that anticholinergics have a selective effect on sustained attention and effortful processing due to lesions in the ascending cholinergic neurons projecting to the frontal lobes. However, the improved verbal fluency with muscarinic blockade suggests a disinhibition or release phenomenon of certain frontal lobe functions due to deregulation of other non-cholinergic neurotransmitters projecting to the frontal lobes. It is suggested that treatment with anticholinergics thus serves to amplify the already compromised cholinergic system in PD and at the same time disinhibit possible catecholamine activity in the frontal lobes resulting in improvement in specific areas of frontal lobe function.

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