Reduced perfusion in the anterior cingulate cortex of patients with pure autonomic failure: an 123I-IMP SPECT study.

BACKGROUND: Pure autonomic failure (PAF) is a selective peripheral disorder in which Lewy bodies form within the autonomic ganglia. Patients with this disorder usually have no central lesions; however, chronic autonomic failure may secondarily affect the central nervous system. This study evaluated brain perfusion in patients with PAF by using N-isopropyl-p-(123)I iodoamphetamine ((123)I-IMP) single photon emission computed tomography (SPECT). METHODS: Six patients with PAF (all men; mean (SD) age 68+/-5 years) who had experienced autonomic symptoms for more than 5 years and six age-matched healthy control subjects (all men; mean (SD) age 67+/-5 years) were included in this study. The regions of interest (ROI) on spacially normalized (123)I-IMP SPECT images were automatically computed for both groups. RESULTS: Perfusion of the dorsal anterior cingulate cortex was decreased in the PAF group compared with the healthy control group (0.93 vs 1.01; p<0.001). In the other brain regions measured, there was no significant difference in regional perfusion between the two groups. CONCLUSIONS: The dorsal anterior cingulate cortex is poorly perfused and may be functionally altered in patients with PAF. The reduced perfusion in such individuals may be a secondary change that results from chronic autonomic failure.

Kinetic analysis of [(11)C]MP4A using a high-radioactivity brain region that represents an integrated input function for measurement of cerebral acetylcholinesterase activity without arterial blood sampling.

N -[(11)C]methylpiperidin-4-yl acetate ([(11)C]MP4A) is an acetylcholine analog. It has been used successfully for the quantitative measurement of acetylcholinesterase (AChE) activity in the human brain with positron emission tomography (PET). [(11)C]MP4A is specifically hydrolyzed by AChE in the brain to a hydrophilic metabolite, which is irreversibly trapped locally in the brain. The authors propose a new method of kinetic analysis of brain AChE activity by PET without arterial blood sampling, that is, reference tissue-based linear least squares (RLS) analysis. In this method, cerebellum or striatum is used as a reference tissue. These regions, because of their high AChE activity, act as a biologic integrator of plasma input function during PET scanning, when regional metabolic rates of [(11)C]MP4A through AChE (k(3); an AChE index) are calculated by using Blomqvist's linear least squares analysis. Computer simulation studies showed that RLS analysis yielded k(3) with almost the same accuracy as the standard nonlinear least squares (NLS) analysis in brain regions with low (such as neocortex and hippocampus) and moderately high (thalamus) k(3) values. The authors then applied these methods to [(11) C]MP4A PET data in 12 healthy subjects and 26 patients with Alzheimer disease (AD) using the cerebellum as the reference region. There was a highly significant linear correlation in regional k(3) estimates between RLS and NLS analyses (456 cerebral regions, [RLS k(3) ] = 0.98 x [NLS k(3) ], r = 0.92, P < 0.001). Significant reductions were observed in k(3) estimates of frontal, temporal, parietal, occipital, and sensorimotor cerebral neocortices (P < 0.001, single-tailed t-test), and hippocampus (P = 0.012) in patients with AD as compared with controls when using RLS analysis. Mean reductions (19.6%) in these 6 regions by RLS were almost the same as those by NLS analysis (20.5%). The sensitivity of RLS analysis for detecting cortical regions with abnormally low k 3 in the 26 patients with AD (138 of 312 regions, 44%) was somewhat less than NLS analysis (52%), but was greater than shape analysis (33%), another method of [(11)C]MP4A kinetic analysis without blood sampling. The authors conclude that RLS analysis is practical and useful for routine analysis of clinical [(11)C]MP4A studies.

Positron emission tomographic measurement of brain acetylcholinesterase activity using N-[(11)C]methylpiperidin-4-yl acetate without arterial blood sampling: methodology of shape analysis and its diagnostic power for Alzheimer's disease.

N-[11C]methylpiperidin-4-yl acetate ([11C]MP4A) is a radiotracer that has been used successfully for the quantitative measurement of acetylcholinesterase (AChE) activity in the human brain with positron emission tomography (PET) using a standard compartment model analysis and a metabolite-corrected arterial input function. In the current study, the authors evaluated the applicability of a simple kinetic analysis without blood sampling, namely shape analysis. First, the authors used computer simulations to analyze factors that affect the precision and bias of shape analysis, then optimized the shape analysis procedure for [11C]MP4A. Before shape analysis execution, the later part of dynamic PET data except for the initial 3 minutes were smoothed by fitting to a bi-exponential function followed by linear interpolation of 8 data points between each of adjacent scan frames. Simulations showed that shape analysis yielded estimates of regional metabolic rates of [11C]MP4A by AChE (k3) with acceptable precision and bias in brain regions with low k3 values such as neocortex. Estimates in regions with higher k3 values became progressively more inaccurate. The authors then applied the method to [11C]MP4A PET data in 10 healthy subjects and 20 patients with Alzheimer's disease (AD). There was a highly significant linear correlation in regional k3 estimates between shape and compartment analyses (300 neocortical regions, [shape k3] = 0.93 x [NLS k3], r = 0.89, P < 0.001). Significant reductions in k3 estimates of frontal, temporal, parietal, occipital, and sensorimotor cerebral cortices in patients with AD as compared with controls were observed when using shape analysis (P < 0.013, two-tailed t-test), although these reductions (17% to 20%) were somewhat less than those obtained by compartment analysis (22% to 27%). The sensitivity of shape analysis for detecting neocortical regions with abnormally low k3 in the 20 patients with AD (92 out of 200 regions, 46%) also was somewhat less than compartment analysis (136 out of 200 regions, 68%). However, taking its simplicity and noninvasiveness into account, the authors conclude that quantitative measurement of neocortical AChE activity with shape analysis and [11C]MP4A PET is practical and useful for clinical diagnosis of AD.

Normal CAG repeat length in the Huntington's disease gene in senile chorea.

There is a widely held belief that most patients presenting with senile chorea have late-onset Huntington's disease (HD) with an unknown family history. We measured CAG trinucleotide repeat expansion in the HD gene in four patients with a clinical presentation of senile chorea and found that CAG repetition lengths were normal. These findings support senile chorea as being a distinct clinical entity that is nosologically separate from late-onset HD.

Effect of donepezil on brain acetylcholinesterase activity in patients with AD measured by PET.

Acetylcholinesterase (AChE) activities in the brain of three patients with AD were measured once before and once during donepezil treatment (5 mg/d in two patients, 3 mg/d in one patient) using PET and N-[11C]methylpiperidin-4-yl acetate. Donepezil reduced k(3) values, an index of AChE activity, in the cerebral cortex by 39 +/- 5%. All patients showed some degree of symptomatic improvement, and it was concluded that this improvement was likely caused by improved cholinergic activity by inhibition of AChE in the brain.

Presynaptic and postsynaptic striatal dopaminergic function in patients with manganese intoxication: a positron emission tomography study.

We performed PET on four patients with chronic industrial Mn intoxication; presynaptic and postsynaptic dopaminergic function were measured with [18F]6-fluoro-L-dopa (6FD) and [11C]raclopride (RAC). All patients had a rigid-akinetic syndrome; they had no sustained benefit from L-dopa. Influx constants (Ki) of 6FD were normal in the caudate and putamen. RAC binding was mildly reduced in the caudate and normal in the putamen. We conclude that nigrostriatal dopaminergic dysfunction is not responsible for the parkinsonism caused by chronic Mn intoxication. The pathology is likely to be downstream of the dopaminergic projection.

Lamotrigine trial in idiopathic parkinsonism: a double-blind, placebo-controlled, crossover study.

Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of idiopathic parkinsonism (IP). We investigated the effects of lamotrigine (LTG), a glutamate-release inhibitor, in the symptomatic treatment of IP in two double-blind, placebo-controlled studies. Single doses of L-dopa/carbidopa (equal to 50% of the usual morning dose) were administered together with either LTG (100, 200, or 400 mg) or two random placebo doses in 14 patients with IP. The patients were assessed using the Modified Columbia Rating Scale (MCRS) and the Purdue Pegboard Test (PPBT) at multiple intervals over 8 hours. There were no significant differences between the placebo doses and the three doses of LTG on the MCRS and PPBT scores. In a 3-month study, 12 patients took LTG titrated up to 400 mg or placebo with their antiparkinsonian medication for 3 months and were then crossed over. Nine of 12 patients did not complete the study because of dyskinesia (n = 2), hallucinations (n = 3), and deterioration of parkinsonian symptoms (n = 4) on LTG. There was no significant difference between placebo and LTG on the MCRS and PPBT in the three patients who completed the study. The results failed to demonstrate any symptomatically beneficial effects of LTG in IP.

Fluorodopa and raclopride PET analysis of patients with Machado-Joseph disease.

We performed [18F]6-fluoro-L-dopa (6-FD) and [11C]raclopride (RAC) PET studies in six patients with Machado-Joseph disease (MJD) (age, 17 to 61 years; duration of illness, 3 to 10 years), normal controls (n = 10 in 6-FD-PET, n = 8 in RAC-PET), and patients with idiopathic parkinsonism (n = 15 in 6-FD-PET). The youngest patient with MJD had prominent dystonia and pyramidal features (type 1 MJD), whereas the remainder were prominently ataxic (types 2 and 3 MJD). Striatal RAC binding was normal in patients with MJD. Striatal 6-FD influx constants (Ki) were low in the range of idiopathic parkinsonism in two patients with MJD (youngest and oldest patients), whereas striatal Ki were normal in the remaining patients with MJD. The impairment of the nigrostriatal dopaminergic pathway did not correlate with the phenotype, CAG repeat length, disease duration, or age of onset of patients with MJD. Our results suggest that striatal D2 receptors are normal and the nigral damage is diverse in MJD.

MRI and PET studies of manganese-intoxicated monkeys.

Using MRI and PET, we investigated the consequences of manganese intoxication in a primate model of parkinsonism and dystonia. Three rhesus monkeys were injected intravenously with doses of 10 to 14 mg/kg of MnCl2 on seven occasions, each a week apart. Two animals became hypoactive with abnormal extended posturing in the hind limbs. These motor disturbances did not improve with administration of levodopa. In all three monkeys, T1-weighted MRI demonstrated high signal intensities in the regions of the striatum, globus pallidus, and substantia nigra. No significant changes were found on [18F]6-fluoro-L-dopa, [11C]raclopride, or [18F]fluorodeoxyglucose PET. These results are consistent with the pathologic findings, which were primarily confined to the globus pallidus, and indicate that manganese intoxication is associated with preservation of the nigrostriatal dopaminergic pathway, despite clinical evidence of parkinsonian deficits. Chronic manganese intoxication may cause parkinsonism by damaging output pathways downstream to the nigrostriatal dopaminergic pathway. This is consistent with the demonstrated lack of therapeutic response to levodopa.

Manganese intoxication in the rhesus monkey: a clinical, imaging, pathologic, and biochemical study.

We gave three adult rhesus monkeys seven IV injections of manganese chloride at approximately 1-week intervals. We evaluated neurologic status by serial clinical examinations and performed a levodopa test if the animal developed features of basal ganglia dysfunction. After the animals were killed, we performed neuropathologic, neurochemical, and laser microprobe mass analysis (LAMMA) studies. Two of three animals developed a parkinsonian syndrome characterized by bradykinesia, rigidity, and facial grimacing suggestive of dystonia but not tremor. Neither animal responded to levodopa. Autopsy demonstrated gliosis primarily confined to the globus pallidus (GP) and the substantia nigra pars reticularis (SNr). We detected focal mineral deposits throughout the GP and SNr, particularly in a perivascular distribution. LAMMA studies noted that mineral deposits were primarily comprised of iron and aluminum. The severity of pathologic change correlated with the degree of clinical dysfunction. These studies demonstrate that, in contrast to Parkinson's disease (PD) and MPTP-induced parkinsonism, manganese primarily damages the GP and SNr and relatively spares the nigrostriatal dopaminergic system. Further, the results suggest that Mn-induced parkinsonism can be differentiated from PD and MPTP-induced parkinsonism by the clinical syndrome and response to levodopa. The accumulation of iron and aluminum suggests that iron/aluminum-induced oxidant stress may contribute to the damage associated with Mn toxicity.

Quantitative in vivo analysis of benzodiazepine binding sites in the human brain using positron emission tomography.

Central-type benzodiazepine binding sites were characterized in a single normal human subject, using positron emission tomography (PET) and the radiolabelled benzodiazepine antagonist, carbon-11 labelled flumazenil ([11C] Ro 15-1788). The subject was scanned using tracer alone and tracer plus 4 different concentrations of unlabelled Ro 15-1788, including one concentration of unlabelled Ro 15-1788, chosen to produce maximum displacement of [11C] Ro 15-1788 from specific binding sites. Concentrations of free, unmetabolized [11C] Ro 15-1788 in plasma were estimated using a simple extraction and ultrafiltration method. Radioactivity in the regional exchangeable pool in brain was estimated under non-saturation conditions from the ratio of radioactivity in brain to plasma, under saturation conditions and the kinetics of free ligand in plasma. The specific binding was, then, estimated by the difference between the total radioactivity in brain and exchangeable pool radioactivity. Scatchard analyses were performed to yield Bmax and Kd values under pseudo-equilibrium conditions, which was observed as an increase of specific binding/free with reduction in specific binding. In cerebral cortex and cerebellum, the Bmax values were about 62-73 nmol/l and the Kd values were 3.6-6 nM in the estimation of free ligand in plasma and 12-15 nM in the estimation of exchangeable pool in brain, as free in brain.

Visualization of specific binding sites of benzodiazepine in human brain.

Using 11C-labeled Ro15-1788 and positron emission tomography, studies of benzodiazepine binding sites in the human brain were performed on four normal volunteers. Rapid and high accumulation of 11C activity was observed in the brain after i.v. injection of [11C]Ro15-1788, the maximum of which was within 12 min. Initial distribution of 11C activity in the brain was similar to the distribution of the normal cerebral blood flow. Ten minutes after injection, however, a high uptake of 11C activity was observed in the cerebral cortex and moderate uptake was seen in the cerebellar cortex, the basal ganglia, and the thalamus. The accumulation of 11C activity was low in the brain stem. This distribution of 11C activity was approximately parallel to the known distribution of benzodiazepine receptors. Saturation experiments were performed on four volunteers with oral administration of 0.3-1.8 mg/kg of cold Ro15-1788 prior to injection. Initial distribution of 11C activity following injection peaked within 2 min and then the accumulation of 11C activity decreased rapidly and remarkably throughout the brain. The results indicated that [11C] Ro15-1788 associates and dissociates to specific and nonspecific binding sites rapidly and has a high ratio of specific receptor binding to nonspecific binding in vivo. Carbon-11 Ro15-1788 is a suitable radioligand for the study of benzodiazepine receptors in vivo in humans.

Kinetics of [11C]N,N-dimethylphenylethylamine in mice and humans: potential for measurement of brain MAO-B activity.

Carbon-11-labeled N,N-dimethylphenylethylamine ([11C]DMPEA) was synthesized by the reaction of N-methylphenylethylamine with [11C]methyl iodide. This newly synthesized radiotracer was developed for the purpose of in vivo measurement of monoamine oxidase-B activity in the brain using a metabolic trapping method. Initially, biodistribution was investigated in mice. The rapid and high uptake of 11C radioactivity in the brain was observed following intravenous injection of [11C]DMPEA, the peak of which was reached at 1 min, followed by a decrease at 1-5 min and slowly thereafter. The kinetics of [11C]DMPEA in the human brain were determined using positron emission tomography (PET) and showed that 11C radioactivity increased gradually over 60 min following initial rapid uptake of 11C radioactivity, with basal ganglia and thalamus showing high accumulation.

Detection of benzodiazepine receptor occupancy in the human brain by positron emission tomography.

Benzodiazepine receptor occupancy in the brain following oral administration of clonazepam (CZP) with a dose of 30 micrograms/kg in six healthy young men and a further dose of 50 micrograms/kg in one of the subjects was estimated by carbon-11 labeled Ro15-1788 and positron emission tomography (PET). The effects of CZP on the latency of auditory event-related potentials (P300) were also studied. Overall brain 11C uptake was depressed and the % inhibition of 11C uptake in the gray matter of the brain at 30 min after [11C]Ro15-1788 injection was 15.3-23.5% (mean, n = 6) following 30 micrograms/kg CZP when compared with that in the control experiment without any previous treatment. The 11C uptake in the cerebral cortex in the subject who received both doses decreased in a dose-related manner after 30 micrograms/kg and 50 micrograms/kg CZP. The P300 latency was prolonged significantly by 30 micrograms/kg CZP [31.6 +/- 16.3 ms (mean +/- SD, n = 6), P less than 0.05]. The P300 latency in the same subject was prolonged in a dose-related manner by 30 micrograms/kg and 50 micrograms/kg CZP. The technique using [11C]Ro15-1788 and PET permits comparison of the pharmacological effects with the percentage of receptor sites which benzodiazepines occupy in the human brain. P300 also seems to be useful to investigate the pharmacological effects of benzodiazepines.

The amygdala and Alzheimer's disease: positron emission tomographic study of the cholinergic system.

The primary transmitter deficit is cholinergic in Alzheimer's disease (AD), and the amygdala receives a major cholinergic projection from the nucleus basalis of Meynert (Ch4), which may play an important role in the retention of affective conditioning and/or memory consolidation. We measured brain acetylcholinesterase (AChE) activity in 54 patients with AD and in 22 normal controls by positron emission tomography and N-[(11)C]methylpiperidin-4-yl acetate to characterize the cholinergic pathology in AD. The k(3) values were calculated as an index of AChE activity in a three-compartment model analysis using the metabolite-corrected arterial input function. The k(3) values were highly significantly reduced by 20% in the cerebral neocortex (P <0.0001 in the two-tailed t test), 14% in the hippocampus (P <0.001), and 33% in the amygdala (P <0.0001) in AD patients compared with normal controls. The k(3) values were significantly correlated with the Mini-Mental State Examination scores in both the cerebral cortex (P <0.001) and the amygdala (P <0.05) in AD patients, supporting the cholinergic hypothesis of cognitive dysfuncion in AD. Further studies are required, however, to elucidate the specific role of the cholinergic deficit in the amygdala in the emotional and behavioral symptoms in AD.

Intracranial dural arteriovenous fistula (DAVF) presenting progressive dementia and parkinsonism.

We studied three patients with dural arteriovenous fistula (DAVF). Major symptoms were progressive dementia and parkinsonism, both of which progressed in step-wise fashion. Two of the three patients showed diffuse cerebral white matter lesions on brain CT and MRI. Progressive dementia and parkinsonism in our patients could be caused by diffuse cerebral parenchymal disturbance: impaired cerebral circulation due to severe venous hypertension. DAVF is important for the differential diagnosis in patients with progressive dementia and parkinsonism.

SPECT imaging of the dopamine transporter with [(123)I]-beta-CIT reveals marked decline of nigrostriatal dopaminergic function in Parkinson's disease with urinary dysfunction.

We studied a correlation of urinary dysfunction with nigrostriatal dopaminergic deficit in Parkinson's disease (PD) by single-photon emission computed tomography (SPECT) imaging of dopamine transporter with [123I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta-CIT). Eleven patients were enrolled in the study, including four men and seven women, with a mean age of 64 years. Seven patients had urinary symptoms 1-5 years after the onset of motor disorder, which included nighttime frequency in six, urinary retardation in four, daytime frequency in one and urge urinary incontinence in one. Using a SPECT camera, the ratio specific to nondisplaceable [123I]-beta-CIT uptake, designated as "striatal V3" was obtained in the caudate, anterior and posterior putamen 24 h after the tracer injection. The striatal V3 was compared in patients with and without urinary dysfunction, and between men and women, using unpaired Student's t-test. Correlation of motor dysfunction and duration of illness with urinary dysfunction, was also analyzed. In the patients, there was a reduction of [123I]-beta-CIT binding in the striatum on both sides, particularly in the putamen contralateral to the affected body side. The striatal V3 of the caudate (p<0.01, Rt; p<0.05, Lt), anterior putamen (p<0.05, Rt) and posterior putamen (p<0.05, Rt) in patients with urinary dysfunction was significantly reduced than those without urinary dysfunction. No sex difference was seen in reduction of [123I]-beta-CIT binding. Urinary dysfunction in PD was more common in patients with higher Unified Parkinson's Disease Rating Scale (UPDRS) score, higher Hoehn-Yahr grade, but not in those with longer duration of disease, although there was no statistical significance. It is likely that our results reflect the association of urinary dysfunction and degeneration of the nigrostriatal dopaminergic cells in PD.

The presymptomatic period in a patient with idiopathic parkinsonism.

A 68-year-old, normal female volunteer was scanned by positron emission tomography (PET) with [(18)F]6-L-fluorodopa (FD). Striatal FD uptake was in the high normal range. Subsequently, she developed parkinsonism 3.7 years after the scan. A repeat FD PET scan revealed a significant reduction of FD uptake by 20% over the 5.2 year interval. Our observations suggest a relatively short presymptomatic period with fast initial losses of nigral neurons in idiopathic parkinsonism.

"Familial Parkinson's disease"--a case-control study of families.

BACKGROUND: Parkinson's disease (PD) patients frequently report a family history of PD and this may provide etiological clues to PD. It has also been suggested that a report of a negative family history is reliable. We studied the prevalence of PD in relatives of PD patients to assess the reliability of family history and to evaluate possible explanations of "familial PD" (fPD). METHODS: 81 of 650 (12.5%) PD probands (all PD patients seen at clinic in 4 years) reported a positive family history of PD. Each fPD proband was matched with non-familial PD (nfPD) proband by gender and year of birth. Screening and follow-up questionnaires were mailed to relatives to obtain information concerning pedigree and presence of neurodegenerative disease. Available family members (regardless of disease status) were examined. RESULTS: On examination, 8 persons, said to be "normal" by probands, relatives and themselves, had definite or possible PD (5 fPD, 3 nfPD). The prevalence rate of PD among first and second degree living relatives of probands varied significantly between fPD and nfPD groups (6269/100,000 versus 1190/100,000; p < 0.001). The weighted prevalence (taking into account the proportions of fPD and nfPD within the clinic) was 1822/100,000, a value more than 5 times higher than reported prevalence rates of PD in the general population (p < 0.001). The prevalence rate was greater in first degree relatives than second degree. CONCLUSIONS: "Familial parkinsonism" cannot be explained merely by size of or advanced age within families. Significant numbers of previously unrecognized PD patients may be identified despite a "negative" family history. That is, the patient's report of an absence of familial parkinsonism is frequently inaccurate. The prevalence rate in relatives of PD patients appears to be higher than the general population-regardless of the family history reported by a PD patient. We believe our study suggests that genetic influences or early life environmental exposures are likely to be of etiological importance in PD.

Questionnaire-based assessment of pelvic organ dysfunction in Parkinson's disease.

Although patients with Parkinson's disease (PD) experience pelvic organ dysfunction of the urinary bladder, bowel and genital organs, an accurate incidence of the dysfunction and its characteristics have yet to be ascertained. We devised a detailed questionnaire on these three pelvic organ functions in PD patients and control subjects, in our search for a hallmark that would distinguish between the two groups. The PD group comprised 115 patients; 52 men and 63 women, age range 35-69 (average 59) years old, average duration of illness 6 years, median Hoehn and Yahr stage 3. All were taking levodopa with/without dopamine agonists. The control group comprised 391 local individuals who were undergoing an annual health survey; 271 men and 120 women, age range 30-69 (average 48) years old. The questionnaire had three parts: bladder (nine questions), bowel (four questions), and sexual (three questions for women, five for men) function. Each question was scored from 0 (none) to 3 (severe) with an additional quality of life (QOL) index scored from 0 (satisfied) to 3 (extremely dissatisfied). The completion rate was 100% for bladder and bowel functions, whereas for sexual function, it was 95% (control) and 88% (PD) for men and 82% (control) and 60% (PD) for women. As compared with the control group, the frequency of dysfunction in the PD group was significantly higher for urinary urgency (women 42%, men 54%), daytime frequency (28%, 16%), nighttime frequency (53%, 63%), urgency incontinence (25%, 28%), retardation (44% of men), prolongation/poor stream (men 70%), straining (women 28%); constipation (63%, 69%), difficulty in expulsion (men 57%), diarrhea (men 21%); decrease in libido (84%, 83%), decrease in sexual intercourse (55%, 88%), decrease in orgasm (men 87%), and in men, decreases in erection (79%) and ejaculation (79%). The QOL index for the PD patients was significantly higher for bladder (27%, 28%) and bowel (46%, 59%) but not for sexual dysfunction, despite the group's high prevalence of sexual dysfunction. In the PD patients, fecal incontinence was associated with urinary incontinence. Stress urinary incontinence and a decrease in libido were more common in women than in men. Bladder and bowel dysfunction, but not sexual dysfunction increased with the Hoehn and Yahr stage. Sexual dysfunction, but neither bladder nor bowel dysfunction, increased with age. Patients taking levodopa and bromocriptine more frequently had bladder (voiding phase) dysfunction than those taking levodopa only. The findings show that bladder, bowel and sexual dysfunction are all prominent in patients with PD. Amelioration of pelvic organ dysfunction, particularly bowel dysfunction which most affects the quality of life, therefore should be a primary target in the treatment of patients with PD.