Late Parkinson's Disease Patients Research Articles

Parkinson's disease duration determines effect of dopaminergic therapy on ventral striatum function

We investigated the hypothesis that variation in endogenous dopamine (DA) across brain regions explains dissimilar effects of dopaminergic therapy on aspects of cognition in early Parkinson's disease (PD). Extensive degeneration of DA-producing cells in the substantia nigra cause dorsal striatum (DS) DA deficiency and movement abnormalities. Particularly in early PD, this contrasts with relative sparing of the dopaminergic cells of the ventral tegmental area (VTA). The hypothesis predicts that DS-mediated cognitive functions are deficient at baseline and improved by DA replacement, whereas functions depending upon VTA-innervated brain regions are normal off medication and worsen with treatment. The latter pattern presumably owes to overdose of relatively DA-replete VTA-supplied brain regions with medication levels titrated to DS-mediated motor symptoms. As PD progresses, however, VTA degeneration increases. Impairment in cognitive operations performed by VTA-innervated brain regions, such as the ventral striatum (VS), is expected. We compared the performance of early and late PD patients, on and off dopaminergic medication, relative to age-matched controls, on reward learning, previously shown to implicate the VS. As expected, in early PD, stimulus-reward learning was normal off medication, but worsened with DA replacement. At more advanced disease stages, PD patients learned stimulus-reward contingencies more poorly than controls and early PD patients off medication. Furthermore, dopaminergic medication did not worsen reward learning in late PD patients, in line with the dopamine overdose hypothesis. Unlike its effect on DS-mediated functions, however, DA-replacement therapy did not improve reward learning in late PD patients.

Treatment options in late Parkinson's disease: decimeter wave therapy

Late stage Parkinson's disease (PD) is characterized by significant worsening of symptoms, motor fluctuations and decrease of effectiveness of drug therapy. Decimeter wave therapy (DWT) is one option to enlarge treatment strategy in late PD. We studied the effect of DWT in 12 patients (7 males), aged 65,83± 4,02 years, with 6,42± 1,51 years disease duration. Seven were at Hoehn-Yahr stage III and remaining 5 at stage IV. Mean UPDRS total score sum was 39,25± 1,91, and mean UPDRS part III sum was 24,67± 2,1. DMW was performed according to a standard protocol with apparatus Volna - 2, 10 consecutive procedures, once daily. Evaluation of UPDRS total and part III was performed on baseline, on days 11, 31 and 61. On day 11 all patients showed decrease in their both UPDRS total and part III. We lowered the levodopa doses of 6 patients in Hoehn-Yahr stage III with greatest decrease of UPDRS. On days 31 and 61 UPDRS total and part III were still lower. Our results demonstrate substantial effect of DWT on motor symptoms in late PD patients. All patients showed improvement, assessed by UPDRS, as the effect still lasted for 2 months after the physical therapy, even slightly diminished on day 61, compared to day 11. According to our results and patients subjective satisfaction reported, we could propose DWT become a part of the treatment strategy in late PD patients.

Approaching disturbed sleep in late Parkinson's Disease: first step toward a proposal for a revised UPDRS

A patient in stage 3–4 of the Unified Parkinson's Disease Rating Scale (UPDRS), or in stage 4–5 of Hoehn and Yahr staging scale, or a patient with 0–50% activities of daily living scale of Schwab and England is considered a Late Parkinson's Disease (LPD) patient. The prevalence of disturbed sleep in Parkinson's Disease (PD) was found to vary according to an objective rating, from 60 to 98%. The factors predicting the quality of life in PD patients are: depression, sleep disturbances and dependence. The present article proposes the insertion of the following items as a chapter in a revised UPDRS based on updated knowledge in sleep arousal disturbances in PD. V. SLEEP-AROUSAL DISTURBANCES: Sleep disturbances 43. Light fragmented sleep (LFS) 44. Sleep-related breathing disorders (SRBD) 45. Restless legs-periodic leg movements during sleep (RLS-PLM) 46. REM behavior disorders (RBD) 47. Sleep-related hallucinations (SRH) 48. Sleep-related psychotic behavior (SRPB) Arousal disturbances 49. Sleep attacks (SA) 50. Excessive daytime sleepiness (EDS) Approaching the treatment of disturbed sleep in LPD means postponement of the institutionalization of the LPD patient, allowing the spouse or the caregiver a quiet nights sleep. This approach consists of three steps, each one of major importance. (1) Correct diagnosis based on detailed anamnesis of the patient, of the spouse or of the caregiver; a one week recording on a symptom diary (log) by the patient or the caregiver; excluding co morbidities. Then choosing the most appropriate sleep test, if necessary: polysomnography (PSG), multiple sleep latency test (MSLT), multiple wake latency test (MWLT), actigraphy or video-PSG. This first step allows the diagnosis of one of the above mentioned sleep-arousal disturbances. (2) The non-specific therapeutic approach consists of: (a) checking the sleep effect on motor performance: beneficial, worse or neutral. (b) Dopaminergic adjustment is necessary due to the progression of the nigrostriatal degeneration and the increased sensitivity of the terminals which alter the normal modulator mechanisms of motor centers in LPD patients. Among the many neurotransmitters of the nigro-striatal pathway one can distinguish two with a major influence on REM and non-REM sleep. REM sleep corresponds to an increased cholinergic receptor activity and a decreased dopaminergic activity. This is the reason why REM sleep deprivation by suppressing cholinergic receptor activity ameliorates LPD motor symptoms. l-Dopa and its agonists by suppressing cholinergic receptors suppress REM sleep. l-Dopa has also an arousal effect on Non-REM sleep, repeatedly awakening the patient and enhancing the fragmentation due to the involuntary movements. (c) Socio–physical assistance. (3) The specific therapy consists of: LFS-Sinemet CR, Tolcapone, Intranasal Desmopressin, Domperidon, Cisapride and neurosurgery; SRBD-CPAP, UPPP, nasal interventions, losing weight; RLS-PLM-Benzodiazepine (Clonazepam), Opioid, Apomorphine infusion; RBD-Clonazepam and dopaminergic agonists; SRH-Clozapine, Risperidone; SRPD-Nortriptyline, Clozapine, Olanzepine; SA-adjustment; EDS-arousing drugs. Each therapeutic approach must be tailored to the individual LPD patient.

Evaluation of [ 123I]β-CIT binding with SPECT in controls, early and late Parkinson's disease

The main neuropathological feature in Parkinson's disease (PD) is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine in the striatum. Recently, a new radioligand (β-CIT) for single photon emission computed tomography (SPECT) became available for in vivo imaging of the dopamine transporter on nerve endings of dopaminergic neurons in the striatum. The present results demonstrate that [ 123I]-β-CIT SPECT allows a discrimination between early and late PD patients. In our opinion, these preliminary data suggest that [ 123I]-β-CIT SPECT should be used from now on in longitudinal studies (such as the DATATOP study) in which the effects of (putative) neuroprotective interventions in PD are monitored.