Elderly Parkinson's Disease Patients Research Articles

Age-related changes in cognitive function and postural control in Parkinson’s disease

This study objectively analyzed postural instability and cognitive function in patients with Parkinson's disease (PD) and a group of healthy elderly and middle-aged individuals. The study included ten healthy middle-aged individuals (range 42-57years), 14 healthy elderly individuals (range 60-90years) and 15 PD patients (range 58-93years). Center of pressure (COP) parameters were determined by means of computed static posturography during free standing with open and closed eyes. The level of cognitive functioning was examined with mini mental state examination (MMSE) and counting backwards test (CBT). Parkinson's disease patients showed significantly lower MMSE scores compared to healthy middle-aged (p=0.004) and elderly individuals (p=0.03). Mean duration of CBT in PD patients was significantly longer than in healthy subjects. COP parameters correlated with age of subjects and cognitive function (MMSE score). No significant differences in any stabilographic parameters were observed between healthy elderly subjects and PD patients. Age is the most significant factor impacting upon the static balance of older individuals during free standing. Compared to middle-aged and elderly individuals without central nervous system impairment, patients with PD present with significant delay in cognitive processes associated with executive function.

Transcendent Experiences Motivate “Escape” From the Body via Intimate Partnerships

Three studies involving younger and older samples tested a model centered upon individual differences in one's personal history of “immutable self” (IS) experiences, typified by consciousness transcending the usual spatiotemporal bounds associated with embodiment, such that conscious existence no longer seems contingent upon the physical body. In Study 1, optical-acoustic stimulation evoked an IS-related experience that increased the sense of physical containment (i.e., feeling isolated within one's body, separate from the rest of the world) among some individuals. Studies 2 and 3 showed that the heightened sense of physical containment associated with a history of IS experiences predicted intensified motivation to maintain an intimate partnership, previously shown elsewhere to reduce the salience of the body. Key comparisons between elderly Parkinson's disease patients versus their spouses and healthy controls provided suggestive evidence that dopaminergic function may be a critical contributor to this motivational sequence.

Evaluation of cardiac autonomic functions in elderly Parkinson's disease patients

Evaluation of cardiac autonomic functions in elderly Parkinson's disease patients

Rapid onset of efficacy of rasagiline in early Parkinson’s disease

Rasagiline is a monoamine oxidase type-B inhibitor used as monotherapy or in addition to levodopa in the treatment of Parkinson's disease (PD). This naturalistic single-blind study was aimed at evaluating the rapidity of onset effect of rasagiline on motor symptoms in a cohort of early relatively elderly PD patients. 102 outpatients (55 males, median age 71 years) have been selected: 26 were PD therapy-naive and 76 received rasagiline as add-on therapy. The third section of the Unified Parkinson's Disease Rating Scale (UPDRSIII) and the Hoehn-Yahr (HY) scale were assessed at baseline and after 1 and 4 weeks thereafter. The mean UPDRS III total score (-6.7 at week 1 and -8.9 at week 4) and single items, as well as mean HY score (-0.40 at week 1 and -0.67 at week 4), significantly decreased from baseline (p < 0.001). Improvements were significant in both therapy-naive and add-on therapy patients: the mean decreases from baseline to week 4 in UPDRSIII and HY score were -8.8 and -0.46, and -9.0 and -0.74, respectively, in the two subgroups. The mean decrease from baseline in UPDRSIII and HY score did not significantly differ in patients aged > or ≤71 years. Rasagiline had a rapid therapeutic effect from the first week of therapy, which further improved at 4 weeks. The rapid onset of action and the absence of a dose titration are important issues in the management of the PD patient.

Older participants are frequently excluded from Parkinson's disease research

BackgroundThe exclusion of older participants from clinical research is common and limits the generalisation of research findings. We aimed to assess the current potential for older patients to participate in Parkinson's disease (PD) research. MethodWe performed a systematic analysis of data extracted from the World Health Organization Clinical Trials Registry Platform regarding 206 actively recruiting PD research studies. Data regarding study variables and exclusion on the grounds of an upper age limit was extracted from each registry entry and subsequently used for statistical analysis. ResultsExclusion by arbitrary upper age limit is common, with 101 (49%) of studies excluding participants by age and with a mean upper age limit for exclusion of 79.3 years (range 64–95 years). Exclusion by age was significantly more common in studies with an estimated enrolment of fewer than 100 participants; OR 1.92 (95%CI 1.13–3.42) P = 0.018. Rates of exclusion by age were not significantly influenced by study subject, study location, source of funding, study duration or number of centres. ConclusionExclusion of participants from PD research on the basis of an upper age limit is common and particularly problematic in smaller studies. The exclusion of older participants seriously compromises the generalisation of findings from PD research to the large numbers of elderly PD patients seen in clinical practice.

Visual restriction and anterior-posterior body oscillations in Parkinson's disease

Sem visão poucos ajustes antecipatórios e/ou compensatórios ocorrem na doença de Parkinson e as evidências destes ajustes são menores quando a evolução da doença e as oscilações corporais são consideradas. Objetivo: O objetivo deste estudo foi evidenciar os efeitos da restrição visual sobre os ângulos das oscilações corporais ântero-posteriores na postura ereta de parkinsonianos considerando os estágios inicias de evolução da doença. Método: Dez idosos com Doença de Parkinson até o estágio 2 de Hoehn &amp; Yahr (HY) ficaram de pé parados por 30 segundos para medir os ângulos das oscilações corporais com e sem visão. Resultados: ANOVA two-way com medidas repetidas revelou efeito principal de visão (F(1,7) = 8,931; p &lt; 0,02). Conclusão: Os ângulos das oscilações corporais ântero-posteriores sem visão foram maiores do que com visão, estes não diferiram entre si quanto aos estágios de HY e as condições de visão interferiram no controle da postura independente do estágio de evolução da Doença de Parkinson.

Marked Improvement of Psychotic Symptoms After Electroconvulsive Therapy in Parkinson Disease

Psychosis is common and often medically intractable in Parkinson disease (PD). Sometimes, its management is essential for the determination of the prognosis of PD. There have been several lines of studies demonstrating the effectiveness of electroconvulsive therapy (ECT) for depression in PD but very few for psychosis. The purpose of this retrospective study was to examine the effects of acute ECT on PD-associated psychosis. The subjects were 5 elderly PD patients (duration, 2-10 years); 4 of whom were diagnosed as "other substance (antiparkinsonian medications)-induced psychotic disorder, with hallucinations," and as 1 "psychotic disorder due to PD, with hallucinations," according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Two patients had comorbidity of major depressive disorder, single episode. The psychosis, being refractory to antipsychotics, was treated with a course of acute ECT. Psychiatric conditions were evaluated using the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale (HDRS), and the Global Assessment of Functioning (GAF) scale. Motor function was assessed using the Hoehn and Yahr staging. The total BPRS and GAF scores after ECT improved significantly compared with those just before ECT. The Hoehn and Yahr staging also showed significant improvement. No marked adverse effects were seen. Duration of the improvement was between 5 and 30 weeks in followed-up patients. Acute ECT was effective for medically refractory psychosis in patients with PD regardless of the comorbidity of depression. Our results suggest a possible indication of acute ECT for refractory psychosis in patients with PD.

Evidence for a dopaminergic innervation of the pedunculopontine nucleus in monkeys, and its drastic reduction after MPTP intoxication

The involvement of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus (CuN), known as the mesencephalic locomotor area, in the pathophysiology of parkinsonian symptoms is receiving increasing attention. Taking into account the role of dopamine (DA) in motor control and its degeneration in Parkinson's disease, this neurotransmitter could induce dysfunction in the PPN and CuN through a direct dopaminergic innervation of these brainstem structures. This study provides the first demonstration that the PPN and CuN are innervated by dopamine transporter-bearing fibres in normal monkeys, which points to a novel dopaminergic system that targets the lower brainstem. Intoxication with MPTP induced a significant loss of dopamine transporter-positive fibres in the PPN and CuN of young (3-5 years old) acutely or chronically intoxicated monkeys compared with control animals. The more severe DA depletion found after chronic intoxication may explain, at least in part, deficits that appear late in the evolution of Parkinson's disease. A drastic loss of DA fibres was also observed in aged acutely intoxicated monkeys (about 30 years old) suggesting that age- and disease-related loss of dopaminergic fibres might be responsible for symptoms, such as gait disorders, that are more severe in elderly parkinsonian patients.

Entacapone in elderly Parkinsonian patients experiencing levodopa-related wearing-off: a pilot study

Levodopa (LD) provides the most effective symptomatic treatment for Parkinson's disease (PD). Long-term treatment with LD, however, is often associated with the development of response fluctuations. Previous evidence suggests that the short half-life of LD is a major contributor to the development of response fluctuations and the wearing-off phenomenon in particular. Entacapone, a peripheral catechol-O-methyltransferase inhibitor has been shown to reduce OFF time and increase ON time in several therapeutic trials on PD patients treated with LD experiencing motor fluctuations. However, data are missing on the tolerability and efficacy of entacapone in elderly PD patients. This is of particular relevance, as most PD patients develop LD-related motor fluctuations after several years of disease duration. Here we report that addition of entacapone in a group of 45 elderly PD patients with LD-related motor fluctuations is well tolerated and efficacious in reducing the time, frequency and severity of the OFF periods. These data suggest that the drug can be used safely and efficaciously in elderly PD patients.

The neuropathological basis for depression in Parkinson's disease

Depression is found in 30–40% of all patients with Parkinson's disease (PD), but its etiology is unclear. Using neuropathology as a signpost for neurotransmitter function, we investigated the prevalence of pathological features found at postmortem and sought to uncover differences between depressed ( n = 11) and non-depressed ( n = 9) elderly PD patients. The results indicate a higher prevalence of pathological features in depressed compared to non-depressed PD patients, particularly in catecholamine areas of the brain; the locus coeruleus (neuronal loss: odds ratio = 7.2, p = 08; gliosis: odds ratio = 18.0, p = 008); dorsal vagus nerve (gliosis: odds ratio = 7.63, p < 0.05), and substantia nigra pars compacta (gliosis: odds ratio = 2.85, ns). However, neuropathological differences were absent in the dorsal raphe nuclei, amygdala, and cortical regions. Our evidence suggests that depression in PD is related more to catecholaminergic than serotonergic system dysfunction.

Tremor reduction by subthalamic nucleus stimulation and medication in advanced Parkinson’s disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proved to be effective for tremor in Parkinson's disease (PD). Most of the recent studies used only clinical data to analyse tremor reduction. The objective of our study was to quantify tremor reduction by STN DBS and antiparkinsonian medication in elderly PD patients using an objective measuring system. Amplitude and frequency of resting tremor and re-emergent resting tremor during postural tasks were analysed using an ultrasound-based measuring system and surface electromyography. In a prospective study design nine patients with advanced PD were examined preoperatively off and on medication, and twice postoperatively during four treatment conditions: off treatment, on STN DBS, on medication, and on STN DBS plus medication. While both STN DBS and medication reduced tremor amplitude, STN DBS alone and the combination of medication and STN DBS were significantly superior to pre- and postoperative medication. STN DBS but not medication increased tremor frequency, and off treatment tremor frequency was significantly reduced postoperatively compared to baseline. These findings demonstrate that STN DBS is highly effective in elderly patients with advanced PD and moderate preoperative tremor reduction by medication. Thus, with regard to the advanced impact on the other parkinsonian symptoms, STN DBS can replace thalamic stimulation in this cohort of patients. Nevertheless, medication was still effective postoperatively and may act synergistically. The significantly superior efficacy of STN DBS on tremor amplitude and its impact on tremor frequency in contrast to medication might be explained by the influence of STN DBS on additional neural circuits independent from dopaminergic neurotransmission.

Visuomotor learning in immersive 3D virtual reality in Parkinson’s disease and in aging

Successful adaptation to novel sensorimotor contexts critically depends on efficient sensory processing and integration mechanisms, particularly those required to combine visual and proprioceptive inputs. If the basal ganglia are a critical part of specialized circuits that adapt motor behavior to new sensorimotor contexts, then patients who are suffering from basal ganglia dysfunction, as in Parkinson's disease should show sensorimotor learning impairments. However, this issue has been under-explored. We tested the ability of 8 patients with Parkinson's disease (PD), off medication, ten healthy elderly subjects and ten healthy young adults to reach to a remembered 3D location presented in an immersive virtual environment. A multi-phase learning paradigm was used having four conditions: baseline, initial learning, reversal learning and aftereffect. In initial learning, the computer altered the position of a simulated arm endpoint used for movement feedback by shifting its apparent location diagonally, requiring thereby both horizontal and vertical compensations. This visual distortion forced subjects to learn new coordinations between what they saw in the virtual environment and the actual position of their limbs, which they had to derive from proprioceptive information (or efference copy). In reversal learning, the sign of the distortion was reversed. Both elderly subjects and PD patients showed learning phase-dependent difficulties. First, elderly controls were slower than young subjects when learning both dimensions of the initial biaxial discordance. However, their performance improved during reversal learning and as a result elderly and young controls showed similar adaptation rates during reversal learning. Second, in striking contrast to healthy elderly subjects, PD patients were more profoundly impaired during the reversal phase of learning. PD patients were able to learn the initial biaxial discordance but were on average slower than age-matched controls in adapting to the horizontal component of the biaxial discordance. More importantly, when the biaxial discordance was reversed, PD patients were unable to make appropriate movement corrections. Therefore, they showed significantly degraded learning indices relative to age-matched controls for both dimensions of the biaxial discordance. Together, these results suggest that the ability to adapt to a sudden biaxial visuomotor discordance applied in three-dimensional space declines in normal aging and Parkinson disease. Furthermore, the presence of learning rate differences in the PD patients relative to age-matched controls supports an important contribution of basal ganglia-related circuits in learning novel visuomotor coordinations, particularly those in which subjects must learn to adapt to sensorimotor contingencies that were reversed from those just learned.

Impact of Functional Age on the Use of Dopamine Agonists in Patients With Parkinson Disease

Parkinson disease (PD) is primarily a neurodegenerative disorder that affects as many as 1,500,000 people in the United States. It is predominantly a disease of the elderly, and special treatment challenges must be addressed in this patient population. It has been generally accepted that PD patients over the age of 70 will have a shorter lifespan than younger patients and are at less risk for developing treatment-emergent complications by virtue of their lower exposure to medication over the course of the disease. Consequently, elderly patients are often treated aggressively when motor symptoms start to become disabling. Recent statistics, however, suggest that effective treatments for PD have helped to increase the longevity of PD patients, suggesting that elderly patients may, in fact, have sufficient medication exposure to raise concern over levodopa-induced motor complications. If this is the case, physicians should consider treating their elderly PD patients with dopamine agonists, which have several advantages over levodopa therapy, not the least of which is a lower prevalence of motor complications. Dopamine agonists are safe and effective in elderly patients and offer numerous advantages when used as either monotherapy or adjunctive therapy, particularly in patients requiring long-term treatment.

Clinical Trial: Efficacy and Tolerability of Entacapone versus Cabergoline in Elderly Parkinsonian Patients with Fluctuations

Clinical Trial: Efficacy and Tolerability of Entacapone versus Cabergoline in Elderly Parkinsonian Patients with Fluctuations

The Effect of Ascorbic Acid on the Pharmacokinetics of Levodopa in Elderly Patients with Parkinson Disease

Levodopa (LD) is one of the most effective drugs for clinical symptoms in patients with Parkinson disease (PD). Most PD patients are advanced in age and may have trouble with LD absorption because aging influences drug absorption processes. Previous reports have indicated that ascorbic acid (AsA) can reduce LD dosage without losing its effectiveness. The current study sought to determine whether AsA affects LD absorption in elderly PD patients. Sixty-seven elderly PD patients took a tablet orally containing 100 mg LD and 10 mg carbidopa following an overnight fast. Plasma LD concentrations were determined at 6 points up to 3 hours, using high-performance liquid chromatography with electrochemical detection. The area under the curve (AUC), peak drug concentration (Cmax), and time to peak drug concentration (Tmax) were calculated. The pharmacokinetic evaluation was repeatedly performed 1 week later in the same way except for adding 200 mg AsA to the tablet. The changes in AUC, Cmax, and Tmax between the tests were evaluated. Significant changes in these parameters were not observed when analyzed using data from all patients. However, significant increases in AUC and Cmax, and a significant reduction in Tmax by adding AsA were observed in 25 patients with baseline AUC < or =2500 ng.hour/mL. In conclusion, AsA can improve LD absorption in elderly PD patients with poor LD bioavailability. LD therapy in combination with AsA may be one of the strategies for PD treatment.

Increased Alzheimer pathology in Parkinson's disease related to antimuscarinic drugs.

The hypothesis that blockade of muscarinic receptors is associated with increased Alzheimer-type pathology was investigated in Parkinson's disease. Amyloid plaque densities were more than 2.5-fold higher in cases treated with antimuscarinic medication in the long term compared with untreated or short-term treated cases (p = 0.005 and 0.00005, respectively). Neurofibrillary tangle densities were also highest in chronic compared with untreated or acute-treated groups (p = 0.02 and 0.05, respectively). The findings, if replicated, have potential implications for the use of anticholinergic medication in elderly Parkinson's disease patients.

RETRACTED: Risk factors for hip fracture among elderly patients with Parkinson's disease

Incidence of hip fracture among patients with Parkinson's disease (PD) is high, especially in elderly women. To determine the effects of various factors on hip fracture risk, we prospectively studied fractures in a group of 115 elderly patients of both genders with PD (46 men, 69 women; mean age, 71.9 years) for 1 year. At baseline, we recorded body mass index (BMI), Hoehn and Yahr stage, and postmenopausal interval, and also measured bone mineral density (BMD) and serum concentrations of ionized calcium, intact parathyroid hormone (PTH), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP; a bone resorption marker), and 25-hydroxyvitamin D (25-OHD). During the year, hip fractures occurred in 18 patients (2 male and 16 female). We compared baseline variables between patients with and without hip fracture. PD patients with decreased BMI, lower BMD, and low concentrations of serum ionized calcium, and 25-OHD (mean 4.0 ng/ml) with compensatory hyperparathyroidism had increased risk of hip fracture. Female PD patients with long postmenopausal intervals also had increased hip fracture risk. BMI, illness duration, postmenopausal intervals, Hoehn and Yahr stage, 25-OHD, PTH, calcium and ICTP were determinants of BMD in patients with fracture. Elderly PD patients with low BMI, low BMD and serum 25-OHD concentrations ≤5 ng/ml with secondary hyperparathyroidism have increased risk of hip fracture, as do female PD patients with long postmenopausal intervals.

Reversal of a body image disorder (Macrosomatognosia) in parkinson's disease by treatment with ac pulsed electromagnetic fields

Macrosomatognosia refers to a disorder of the body image in which the patient perceives a part or parts of his body as disproportionately large. Macrosomatognosia has been associated with lesions in the parietal lobe, particularly the right parietal lobe, which integrates perceptual-sensorimotor functions concerned with the body image. It has been observed most commonly in patients with paroxysmal cerebral disorders such as epilepsy and migraine. The Draw-a-Person-Test has been employed in neuropsychological testing to identify disorders of the body image. Three fully medicated elderly Parkinsonian patients who exhibited, on the Draw-a-Person Test, macrosomatognosia involving the upper limbs are presented. In these patients spontaneous drawing of the figure of a man demonstrated disproportionately large arms. Furthermore, it was observed that the arm affected by tremor or, in the case of bilateral tremor, the arm showing the most severe tremor showed the greatest abnormality. This association implies that dopaminergic mechanisms influence neuronal systems in the nondomi-nant right parietal lobe which construct the body image. After receiving a course of treatments with AC pulsed electromagnetic fields (EMFs) in the picotesla flux density applied transcranially, these patients' drawings showed reversal of the macrosomatognosia. These findings demonstrate that transcranial applications of AC pulsed EMFs affect the neuronal systems involved in the construction of the human body image and additionally reverse disorders of the body image in Parkinsonism which are related to right parietal lobe dysfunction.

Presynaptic monoaminergic vesicles in Parkinson's disease and normal aging.

We present development and human application of a method for determining the regional cerebral density of the type 2 vesicular monoamine transporter (VMAT2) using positron emission tomography (PET) and [11C]dihydrotetrabenazine (DTBZ). Previous animal studies indicate striatal VMAT2 density is linearly related to the integrity of substantia nigra dopamine neurons and is not subject to drug- or lesion-compensatory regulation. In the present studies, kinetic compartmental modeling was employed to estimate blood-brain [11C]DTBZ transport (K1) and VMAT2 binding site density (tissue-to-plasma DTBZ distribution volume, DV) from the cerebral and plasma DTBZ time courses after intravenous tracer injection. In controls, we found reductions of putamen DTBZ DVwith advancing age, corresponding to losses of 0.77% per year in specific VMAT2 binding. Parkinson's disease (PD) patients had reduction in specific DTBZ DV in the putamen (-61%) and in the caudate nucleus (-43%). There was no overlap of lowest specific putamen DTBZ DV between individual elderly controls and PD patients. The present results indicate the suitability of [11C]DTBZ PET for objective quantification of nigrostriatal integrity, including evaluation of PD progression and its possible therapeutic modification.

Does levodopa therapy delay death in Parkinson's disease? A review of the evidence.

Studies examining the mortality from Parkinson's disease have been reviewed to assess the impact of levodopa therapy. These include national mortality data taken from death certificate returns, cohort studies comparing the deaths observed in a group of patients with those expected from population statistics, and case-control studies comparing deaths in patients with those in a matched control group. It is concluded that the decrease in crude mortality rate in the early 1970s in several western countries was mirrored by a decrease in observed to expected mortality rates in cohort studies over the same period. The rise in crude mortality in the late 1970s and early 1980s paralleled an increase in observed to expected mortality in cohort studies. These trends are compatible with the hypothesis that levodopa delayed the death of a cohort of frail elderly parkinsonian patients who succumbed approximately 5 years later, leading to an apparent "catch-up" increment in national mortality data. Whilst crude mortality in England and Wales does not appear to be increasing as fast as before the introduction of levodopa, recent cohort and case-control studies report mortality ratios comparable to those seen in the prelevodopa era. Further case-control studies are required to determine the position with current treatment regimens.