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Association between amantadine and the onset of dementia in Parkinson's disease

The objective of this study is to compare the occurrence of dementia among Parkinsons disease (PD) patients treated with amantadine (AM group) with those never exposed to it (NoAM group). PD dementia shares neuroanatomical and biochemical similarities with Alzheimers disease (AD). Memantine, an N‐methyl‐D‐aspartate (NMDA) receptor antagonist has been shown to be beneficial in AD. Memantine is a dimethyl derivative of amantadine, which also possesses NMDA receptor blocking properties. We hypothesized that amantadine could have a beneficial effect on the occurrence of PD dementia. PD patients attending the Movement Disorders Clinics in Hillel Yaffe, Asaf Harofe Medical Centers (Israel) and Pisa (Italy) were included. Taking the onset of dementia as the endpoint, survival curves for AM and NoAM patients were estimated by the Kaplan–Meier method. The study population consisted of 593 patients (age, 69.5 ± 9.9 years; PD duration, 9.2 ± 6.0 years; 263 patients (44%) amantadine treated). The endpoint of dementia was reached by 116 patients (20%). PD duration until dementia was significantly longer for AM patients (9.1 ± 5.7 years) than for NoAM patients (5.9 ± 4.6 years, P = 0.006). The duration of amantadine exposure positively correlated with PD duration until dementia (P = 0.0001). Survival analysis, taking dementia onset as endpoint, showed slower mental decline in AM patients (Log rank P = 0.0049, Wilcoxon P = 0.0024). Mini‐Mental State Examination scores were significantly higher for AM patients than for the NoAM group (P = 0.01). Age of PD onset also significantly influenced the duration of PD until dementia. Amantadine use may delay the onset of dementia in PD patients and may attenuate its severity.

A single-center, cross-sectional prevalence study of impulse control disorders in Parkinson disease: association with dopaminergic drugs.

Abstract The current study aimed at establishing the prevalence of impulse control disorders (ICDs) in patients with Parkinson disease (PD) and their association with demographic, drug-related, and disease-related characteristics. We performed a single-center cross-sectional study of 805 PD patients. Impulse control disorders were investigated with the Questionnaire for Impulsive Compulsive Disorders in Parkinson’s Disease; also comorbid neuropsychiatric complications (dementia, delusions, visual hallucinations) were investigated with clinical interviews and ad hoc instruments (Parkinson Psychosis Questionnaire and Neuropsychiatry Inventory). Impulse control disorders were identified in 65 patients (prevalence, 8.1%), with pathological gambling and hypersexuality the most frequent. Impulse control disorders were present in 57 of 593 cognitively preserved patients (prevalence, 9.6%) and in 8 of 212 demented patients (prevalence, 3.8%). Impulse control disorders were significantly associated with dopamine agonists (odds ratio [OR], 5.50; 95% confidence interval [CI], 2.60–12.46; P < 0.0001) and levodopa (OR, 2.43; 95% CI, 1.06–6.35; P = 0.034). Impulse control disorders frequency was similar for pramipexole and ropinirole (16.6% vs 12.5%; OR, 1.45; 95% CI, 0.79–2.74; P = 0.227). Additional variables associated with ICDs were male sex and younger age. These findings suggested that dopaminergic treatments in PD are associated with increased odds of having an ICD, but also other demographic and clinical variables are associated with ICDs, suggesting the multifactorial nature of the ICD phenomenon in PD.

Presynaptic nigro-striatal function in a group of Alzheimer's disease patients with parkinsonism: evidence from a dopamine transporter imaging study

Summary.The occurrence of parkinsonism in Alzheimer’s disease (AD) is quite common, however the molecular and neurochemical changes underlying such extrapyramidal features in AD have been not fully understood. Post-mortem as well as in vivo imaging study have produced conflicting results as regards the existence of dopaminergic changes in AD. Aim of the present study was to investigate in vivo the nigro-striatal dopaminergic function in a group of AD patients with parkinsonism. Thirteen patients with AD and extrapyramidal features not related to past neuroleptic use (AD-P) underwent SPECT with 123I-FP-CIT, a ligand of dopamine transporter, and the data were compared with those obtained in 15 patients with Diffuse Lewy Body Dementia (DLBD), 20 patients with Parkinson’s disease (PD), and 8 healthy elderly controls. The analysis of the data was performed by regions-of-interest approach and calculations of the striatal-to-non specific (occipital lobes) radioactivity ratios were made. The 123I-FP-CIT striatal uptake in patients with AD-P was similar to that obtained in the control population. Both the DLBD and PD groups showed significantly lower 123I-FP-CIT uptake in all striatal areas with respect to AD-P and control groups (p<0.005). The lack of dopamine transporter changes in our series of AD-P patients can indicate that dopaminergic presynaptic function is preserved in this population and that different dopaminergic changes such as postsynaptic ones, or different neurotransmitter alterations might underlie the extrapyramidal features in AD.

Dopaminergic degeneration and perfusional impairment in Lewy body dementia and Alzheimer's disease

Abstract.The clinical differentiation of Lewy body dementia (LBD) from Alzheimer’s disease (AD) may be difficult. The aim of the present study was to assess the dopamine transporter function and the perfusional pattern in LBD and AD in vivo. Twenty patients with probable LBD and 24 with probable AD underwent on 2 separate days a brain perfusional SPECT with 99mTc-ECD and a SPECT with 123I-FP-CIT, a ligand of dopamine transporter. In LBD a significantly (p<0.0005) lower ratio of specific (bilateral caudate nucleus, putamen) to non-specific (occipital cortex) 123I-FP-CIT binding than in AD was reported. Perfusional data (SPM analysis) showed a significant (p<0.001) decrease of temporo-parietal blood flow in AD versus LBD, whereas in LBD a significant (p<0.001) occipital hypoperfusion with respect to AD was reported. Our findings confirm that dopaminergic nigrostriatal function is impaired in LBD. The selective occipital hypoperfusion in LBD needs to be further investigated.

Influences of Dopaminergic Treatment on Motor Cortex in Parkinson Disease : A MRI/MRS Study

The objective of this study was to investigate neurochemical and metabolic changes in the motor cortex in a group of de novo Parkinsons disease (PD) patients before and after 6 mo treatment with the dopamine agonist pergolide. Proton magnetic resonance spectroscopy (1H‐MRS) has been used to study striatal and cortical metabolism in PD and other parkinsonisms. So far, no studies evaluating possible brain metabolic changes in PD patients before and after dopaminergic therapy have been reported. De novo PD patients (11) and controls (11) underwent clinical evaluation (UPDRS‐III motor evaluation) and a first single‐voxel 1H‐MRS of the motor cortex. 1H‐MRS studies were performed using the PROBE‐SV System implemented on a 1.5 Tesla Scanner (GE Medical System, Milwaukee, WI). Pergolide was administered up to a dose of 1 mg t.i.d. After 6 mo follow‐up, all patients were clinically evaluated and a second single‐voxel 1H‐MRS was performed. Lower values of Cho/Cr and NAA/Cr ratios were observed in the motor cortex of PD patients compared with controls (P < 0.02 and P < 0.01, respectively). After 6 mo therapy with pergolide (1 mg t.i.d), PD patients showed an improvement in motor performances (P < 0.05) and an increase in Cho/Cr ratios in the motor cortex at the second 1H‐MRS evaluation (P < 0.05) was reported. In conclusion, cortical NAA/Cr and Cho/Cr ratios may be impaired in de novo PD. Dopaminergic therapy capable of improving motor function may restore the Cho/Cr ratio in the motor cortex.

Brain perfusion effects of cholinesterase inhibitors in Parkinson’s disease with dementia

Summary.Several evidences suggest that cholinergic deficits may significantly contribute to dementia in Parkinson’s disease (PDD) and acetylcholinesterase inhibitors (ChEIs) have been reported to improve cognitive symptoms in PDD, without worsening parkinsonism. Nineteen PDD patients underwent brain perfusion SPECT with 99mTc-ethyl cysteinate dimer after 6 months ChEIs treatment in order to evaluate the functional correlates of clinical improvement. A clear-cut cognitive improvement was reported in PDD patients with a significant improvement of ADAS-cog total score as well as of subscores exploring executive functions (p < 0.01). MMSE total score did not significantly change after ChEIs but the subscore of attention significantly improved after therapy (p < 0.01). No difference in motor performance as evaluated by UPDRS was reported. SPM analysis showed a significant increase of perfusion (p < 0.0001) in bilateral cingulate, and frontal regions after ChEIs. Our data confirm the efficacy of ChEIs in the treatment of dementia associated with PD mainly on attention and executive functions, and the functional findings indicate that this cognitive improvement could be associated with a sort of pharmacological frontal “re-afferentation”.

Levodopa response in dementia with lewy bodies: A 1-year follow-up study

PURPOSE To evaluate levodopa responsiveness in patients with probable dementia with Lewy bodies (DLB) compared to early Parkinsons disease (PD) patients. METHODS Twenty four cases with DLB and 21 with PD underwent a baseline assessment with UPDRS (sub-item II and III) and an acute levodopa challenge test. Positive response to acute levodopa test was defined as an improvement of at least 15% in the tapping test, and at least 25% in the walking test and rigidity or tremor score. Subsequently, all patients were treated continuously with levodopa and evaluated after 6 and 12 months by means of UPDRS II/III. RESULTS Positive response to the acute levodopa test was observed in 55% of DLB patients (acute DLB responders), and in 90% of PD patients (acute PD responders). Acute DLB responders showed increased latency, and reduction of both duration and amplitude of response to acute levodopa in comparison with acute PD responders. At the 6-month follow-up visit, acute DLB responders showed a greater motor benefit compared with acute DLB non-responders. This improvement was similar to that observed in PD patients. However, at 1-year follow-up acute DLB responders showed a faster worsening of UPDRS III scores compared with acute PD responders, implying a reduction of levodopa efficacy. CONCLUSIONS Positive response to acute levodopa test can occur in DLB patients and may be predictive of long-term benefit of chronic levodopa therapy, although the motor improvement is less impressive than in PD patients.

‘Indotest’ in Atypical Hemicrania Continua

Hemicrania continua (HC) is an indomethacin-responsive headache characterized by a chronic, strictly unilateral, side-locked without side-shifting, persistent headache. We report three cases of HC with atypical features in which an acute administration of indomethacin 50 mg IM (INDOTEST) was performed. In all three cases INDOTEST predicted chronic responsiveness to indomethacin. Thus, in cases of HC with atypical features, INDOTEST could help for a correct diagnosis and therapy.

Diagnosis, assessment and management of delusional jealousy in Parkinson's disease with and without dementia

Patients with Parkinson’s disease (PD) may present delusional jealousy (DJ). In a previous cross-sectional prevalence study we identified 15 cognitively preserved and five demented PD patients with DJ. The current study aimed at evaluating their clinical (motor and non-motor) characteristics and the pharmacological treatments associated with DJ, and its subsequent pharmacological management. Patients were assessed by neurologists and psychiatrists using the Hoehn and Yahr scale, the Unified Parkinson’s Disease Rating Scale, the Brief Psychiatric Rating Scale, the Beck Depression Inventory, the Hamilton Anxiety Scale and the Neuropsychiatric Inventory. Efficacy of DJ management was evaluated in follow-up visits. All patients were in therapy with dopamine agonists. A subgroup of five cognitively preserved patients developed DJ after a short period of treatment of therapy with dopamine agonists, while other patients developed DJ after a longer period of dopaminergic treatment. Psychiatric comorbidities were common in cognitively preserved and in demented patients. The pharmacological management included the interruption of dopamine agonists in two patients and the reduction of dopamine agonist dose plus the use of antipsychotics in other patients. These clinical data suggest that the management of medicated PD patients should include investigation for the presence of DJ and the evaluation of clinical characteristics potentially relevant to the prevention or the early recognition of delusions.

Postpartum Headache Due to Spontaneous Cervical Artery Dissection

Postpartum headache is quite common and often related to potentially ominous cerebrovascular accidents. As illustrated in previously published reports, spontaneous cervical artery dissection is a rare but possible cause of headache in the postpartum. We provide 2 additional cases to the 19 described so far, including the first ever report of migraine with aura‐like symptoms. Additionally, we summarize the literature and we speculate about the possible etiopathological mechanism underlying this condition.