Aromatic L-amino acid decarboxylase (AAAD) activity is enhanced in the striatum of control and MPTP-treated mice after administration of a single dose of the dopamine receptor antagonists haloperidol, sulpiride, and SCH 23390. MPTP-treated mice appear more sensitive to the antagonists, i.e., respond earlier and to lower doses of antagonists than control mice. The rise of AAAD activity induced by the antagonists is prevented by pretreatment with cycloheximide. The apparent Km values for L-3,4-dihydroxyphenylalanine (L-DOPA) and pyridoxal 5-phosphate appear unchanged after treatment with the antagonists. Increased AAAD activity was observed also after subchronic administration of dopamine receptor antagonists or treatment with reserpine. A single dose of a selective dopamine receptor agonists had no effect on AAAD activity. In contrast, administration of L-DOPA, quinpirole, or SKF 23390 for 7 days lowers AAAD activity in the striatum. We conclude that AAAD is modulated in striatum via dopaminergic receptors.

Cognitive deficits are common in Parkinson’s disease (PD), but the pathophysiology and relationship to Alzheimer’s disease (AD) are not understood. We used a case-control format to investigate putative risk factors for the development of dementia in patients with Parkinson’s disease. We compared 52 cognitively intact patients with PD to 43 PD patients with dementia with regard to factors previously suggested as relevant to either AD or PD. Multiple logistic regression yielded the following significant predictors of dementia in PD: lack of education (less than a high school graduate) (OR 21); severity of motor deficit (UPDRS total motor score greater than 20; OR 6.34), and PD onset at greater than 60 years of age (OR 4.12). The predictive probability of dementia in our subjects when all three variables were positive was 97.9%. We conclude that education may modify the risk of cognitive decline in PD. Protective effects of educational attainment, independent of dementia etiology, may be due to greater functional brain reserve.

No abstract