ABSTRACT
Stereotypies are simple or complex involuntary/unvoluntary behaviors, common in fronto-temporal dementia (FTD), but not studied in other types of degenerative dementias. The aim was to investigate stereotypy frequency and type in patients with FTD, Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and Parkinson's disease with dementia (PDD) in a multicenter observational study; and to investigate the relation of stereotypies to cognitive, behavioral and motor impairment. One hundred fifty-five consecutive outpatients (45 AD, 40 FTD, 35 PSP and 35 PDD) were studied in four hospitals in northern Italy. Stereotypies were examined by the five-domain Stereotypy Rating Inventory. Cognition was examined by the Mini Mental State and Frontal Assessment Battery, neuropsychiatric symptoms by the Neuropsychiatric Inventory, and motor impairment and invalidity by the Unified Parkinson's Disease Rating Scale part III, and activities of daily living. Stereotypies were present in all groups. FTD and PDD had the greatest frequency of one-domain stereotypies; FTD also had the greatest frequency of two-or-more domain stereotypies; movement stereotypies were the most common stereotypies in all groups. AD patients had fewer stereotypies than the other groups. Stereotypies are not exclusive to FTD, but are also fairly common in PSP and PDD, though less so in AD. Stereotypies may be underpinned by dysfunctional striato-frontal circuits, known to be damaged in PSP and PDD, as well as FTD.
Subject(s)
Alzheimer Disease/epidemiology , Frontotemporal Dementia/epidemiology , Parkinson Disease/epidemiology , Stereotypic Movement Disorder/epidemiology , Supranuclear Palsy, Progressive/epidemiology , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Dementia/diagnosis , Dementia/epidemiology , Dementia/psychology , Female , Frontotemporal Dementia/diagnosis , Frontotemporal Dementia/psychology , Humans , Male , Middle Aged , Neuropsychological Tests , Parkinson Disease/diagnosis , Parkinson Disease/psychology , Stereotypic Movement Disorder/diagnosis , Stereotypic Movement Disorder/psychology , Supranuclear Palsy, Progressive/diagnosis , Supranuclear Palsy, Progressive/psychologyABSTRACT
We have recently reported that parkinsonian patients show a significant GH response to gamma-hydroxybutyric acid (GHB), but not to gamma-aminobutyric acid (GABA)-ergic drug administration. In order to establish whether muscarinic cholinergic receptors mediate the GH secretion induced by GHB, normal men and parkinsonian patients were tested with GHB both in the absence and in the presence of the anticholinergic agent, pirenzepine. Both normal controls and parkinsonian patients showed a significant serum GH rise in response to GHB (25 mg/kg body weight p.o.) even though a slightly, but significantly lower response was observed in parkinsonian patients. Pretreatment with pirenzepine (100 mg p.o. 2 h before GHB) completely suppressed the GHB-induced GH release in both normal controls and parkinsonian patients. These data indicate that a cholinergic mechanism mediates the GH response to GHB in normal men. In addition the data indicate that this pathway is preserved in the parkinsonian brain.
Subject(s)
Human Growth Hormone/blood , Neurosecretory Systems/drug effects , Parkinson Disease/metabolism , Receptors, Muscarinic/drug effects , Sodium Oxybate/pharmacology , Aged , Area Under Curve , Humans , Male , Middle Aged , Muscarinic Antagonists/adverse effects , Muscarinic Antagonists/pharmacology , Pirenzepine/adverse effects , Pirenzepine/pharmacology , Sodium Oxybate/adverse effectsABSTRACT
Whole-brain functional magnetic resonance imaging (MRI) was used to examine the neural substrates of internally (endogenous) and externally (exogenous) induced covert shifts of attention. Thirteen normal subjects performed three orienting conditions: endogenous (location of peripheral target predicted by a central arrow 80% of the time), exogenous (peripheral target preceded by noninformative central cue). Behavioral results indicated faster reaction times (RTs) for valid than for invalid trials for the endogenous condition but slower RTs for valid than for invalid trials for the exogenous condition (inhibition of return). The spatial extent and intensity of activation was greatest for the endogenous condition, consistent with the hypothesis that endogenous orienting is more effortful (less automatic) than exogenous orienting. Overall, we did not observe distinctly separable neural systems associated with the endogenous and exogenous orienting conditions. Both exogenous and endogenous orienting, but not the control condition, activated bilateral parietal and dorsal premotor regions, including the frontal eye fields. These results suggest a specific role for these regions in preparatory responding to peripheral stimuli. The right dorsolateral prefrontal cortex (BA 46) was activated selectively by the endogenous condition. This finding suggests that voluntary, but not reflexive, shifts of attention engage working memory systems.
Subject(s)
Attention/physiology , Brain Mapping , Brain/physiology , Cues , Magnetic Resonance Imaging , Psychomotor Performance/physiology , Spatial Behavior/physiology , Visual Pathways/physiology , Visual Perception/physiology , Adult , Dominance, Cerebral , Female , Fixation, Ocular , Frontal Lobe/physiology , Gyrus Cinguli/physiology , Humans , Male , Models, Neurological , Models, Psychological , Parietal Lobe/physiology , Photic Stimulation , Prefrontal Cortex/physiology , Reaction Time , Space Perception/physiology , Temporal Lobe/physiology , Thalamus/physiology , Visual Pathways/anatomy & histologyABSTRACT
The observation that baclofen stimulates growth hormone (GH) secretion in normal men, but not in parkinsonian patients led us to test the GH releasing effect of other gamma-amino-butyric acid (GABA)ergic agents with different mechanisms of action in Parkinson's disease. For this purpose 10 normal men and 10 de novo parkinsonian patients were tested with sodium valproate (800 mg PO), gamma-hydroxybutyric acid (GHB) (25 mg/kg body weight PO) and baclofen (10 mg PO). All drugs induced a significant increment in serum GH levels in the normal controls. On the other hand, GH secretion in parkinsonian patients did not change after baclofen or sodium valproate administration, whereas it showed normal responsiveness to GHB. These data suggest that the mechanism underlying the GH response to GHB is different from that (or those) mediating sodium valproate and/or baclofen action. In addition, the former, but not the latter mechanism appears to be preserved in the parkinsonian brain.
Subject(s)
Growth Hormone/blood , Parkinson Disease/metabolism , Sodium Oxybate/blood , gamma-Aminobutyric Acid/blood , Aged , Baclofen , GABA Agents , GABA Agonists/pharmacology , Humans , Male , Middle Aged , Parkinson Disease/blood , Valproic AcidABSTRACT
Visual attention in dementia of Alzheimer's disease (AD) has not been investigated as extensively as memory or language. The aim of this research was to study the orienting of attention in patients with AD (which temporo-parietal areas are primarily affected) compared with patients with Parkinson-Dementia, Parkinson's disease, and normal controls, using the Posner paradigm. Subjects were instructed to respond by pressing a response key after the appearance of a target at the same location (valid trial) or at the opposite location (invalid trial) indicated by a central cue (arrow). According to the experimental procedure developed by Posner, it has been hypothesized that parietal lobes are involved in "disengagement operation" (when attention has to move from one location to another in the controlateral field). Results showed no differences between AD and the other groups and between left and right hemifield. In conclusion, the authors did not find any sign of difficulty with disengagement, and results are discussed in terms of Kinsbourne's interpretation of a balance between hemispheres.
Subject(s)
Alzheimer Disease/physiopathology , Arousal/physiology , Attention/physiology , Dominance, Cerebral/physiology , Orientation/physiology , Visual Perception/physiology , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Corpus Callosum/physiopathology , Dementia/diagnosis , Dementia/physiopathology , Dementia/psychology , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Parietal Lobe/physiopathology , Parkinson Disease/diagnosis , Parkinson Disease/physiopathology , Parkinson Disease/psychology , Pattern Recognition, Visual/physiology , Reaction Time/physiology , Temporal Lobe/physiopathologyABSTRACT
In order to establish whether the serotonergic disorder affecting the parkinsonian brain also modifies hypothalamic-pituitary function in Parkinson's disease, 10 patients (aged 57-66 years) and 10 normal controls (aged 55-69 years) were tested with the serotonergic agonist d,l-fenfluramine (60 mg p.o.), with CRH (100 micrograms i.v.) and with placebos. Plasma ACTH/cortisol levels during tests were evaluated and compared. Both groups showed similar levels of ACTH and cortisol in basal conditions and after placebo administration. A slight physiological decline in both ACTH and cortisol levels during the placebo test was observed in normal controls and parkinsonian patients. CRH induced similar ACTH/cortisol increments in all subjects. In contrast, d,l-fenfluramine significantly increased plasma ACTH/cortisol concentrations in the normal controls, but not in the parkinsonian patients. These data show a defective serotonergic control of the pituitary-adrenal axis in Parkinson's disease.
Subject(s)
Adrenocorticotropic Hormone/blood , Fenfluramine , Hydrocortisone/blood , Hypothalamo-Hypophyseal System/physiopathology , Parkinson Disease/physiopathology , Pituitary-Adrenal System/physiopathology , Serotonin Receptor Agonists , Aged , Analysis of Variance , Case-Control Studies , Corticotropin-Releasing Hormone/pharmacology , Humans , Longitudinal Studies , Male , Middle Aged , Parkinson Disease/blood , PlacebosABSTRACT
In order to gain a better insight in the serotonergic disorder affecting the parkinsonian brain, the growth hormone (GH) response to the 5-HT 1 serotonergic receptor agonist sumatriptan was tested. Sumatriptan was injected subcutaneously in 10 de novo parkinsonian patients (aged 58-69 years) and in 9 age-matched normal controls. On different occasions, subjects were also tested with GH-releasing hormone (GH-RH; 1 micrograms/kg body weight in an intravenous bolus) and L-arginine (30 g in 50 ml normal saline over 30 min), which releases GH from somatostatin inhibition, to determine whether GH secretion in response to alternate secretagogues is preserved in Parkinson's disease. In addition, a control test with the administration of normal saline instead of drug treatments was performed. Plasma GH levels were recorded over 2 h in all tests. Placebo administration did not change plasma GH levels in any subject. Similar GH responses were observed in normal controls and parkinsonian patients when GH-RH or arginine were administered. A significant GH increase was observed in normal controls after sumatriptan injection; in contrast, GH secretion was not modified by sumatriptan administration in parkinsonian patients. These data show that Parkinson's disease is associated with an impairment in the 5-HT1-receptor-mediated serotonergic transmission in the control of GH secretion, suggesting that this specific defect might alter other serotonergic-mediated mechanisms in the parkinsonian brain.
Subject(s)
Human Growth Hormone/blood , Parkinson Disease/physiopathology , Pituitary Gland/physiopathology , Serotonin Receptor Agonists , Sumatriptan , Aged , Analysis of Variance , Arginine , Case-Control Studies , Growth Hormone-Releasing Hormone , Humans , Longitudinal Studies , Male , Middle AgedABSTRACT
The function of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated in insulin-dependent diabetics without (group I, n = 10) or with (group II, n = 10) established symptomatic neuropathy and in age- and weight-matched normal controls (n = 11). Since the corticotropin (ACTH)/cortisol response to the minimal-effective dose of corticotropin-releasing hormone ([CRH] 0.03 microgram/kg body weight) represents a useful tool for HPA axis examination, all subjects were tested with the low-dose ovine CRH stimulation test. Experiments started at 8:30 AM, when CRH was injected after two basal blood samples were withdrawn, and lasted 2 hours. Basal serum levels of ACTH were similar in the three groups. Administration of CRH induced a small but significant increase in ACTH levels in all subjects; however, the CRH-induced ACTH increase was significantly higher in normal controls than in diabetic groups I and II. Furthermore, a significantly lower ACTH response was observed in group II than in group I. In contrast, basal and CRH-induced cortisol levels were significantly higher in diabetics than in normal controls. Comparisons between diabetic groups showed that both basal and stimulated cortisol secretion was significantly higher in group II than in group I. When peak ACTH responses to CRH and basal cortisol levels were combined, a significant negative correlation was found (r = .545, P < .02). These data show that even uncomplicated diabetes mellitus is associated with adrenal hyperfunction. Such an alteration is more pronounced in the presence of neuropathy.
Subject(s)
Corticotropin-Releasing Hormone , Diabetes Mellitus/physiopathology , Diabetic Neuropathies/physiopathology , Adrenocorticotropic Hormone/blood , Adult , Animals , Corticotropin-Releasing Hormone/administration & dosage , Diabetes Mellitus/blood , Diabetic Neuropathies/blood , Humans , Hydrocortisone/blood , Male , Reference Values , SheepABSTRACT
Psychiatric symptoms were investigated and compared in 95 patients with Alzheimer type dementia (DAT) and in 39 patients with Parkinson's disease with dementia (PD-D). The diagnosis of the dementia and psychiatric disorders was based on DSM III R criteria; dementia stage was assessed using the Clinical Dementia Rating Scale (CDR). PD-D were significantly older than DAT patients. Delirium was more frequent in the advanced stages of both PD-D and DAT, being mainly of the hypoactive type in PD-D and the hyperactive type in DAT. Delusions and hallucinations predominated in the early CDR stages of both illnesses and did not differ between groups; the same was true for depression. The results revealed different psychopathological profiles in DAT and PD-D patients.
Subject(s)
Alzheimer Disease/psychology , Cognition Disorders/diagnosis , Parkinson Disease/psychology , Aged , Alzheimer Disease/diagnosis , Case-Control Studies , Cognition Disorders/psychology , Dementia/diagnosis , Dementia/psychology , Female , Humans , Male , Middle Aged , Parkinson Disease/diagnosis , Psychiatric Status Rating ScalesABSTRACT
Naloxone is unable to stimulate ACTH/cortisol secretion in patients with de novo Parkinson's disease, suggesting a reduced endogenous opioid control of the hypothalamic-pituitary-adrenal axis in parkinsonian patients. In the present study we examined whether Parkinson's disease also impairs the secretion of LH, which is under the inhibitory control of different opioid peptides than ACTH/cortisol. In addition, we examined whether a chronic dopaminergic therapy for at least one year with levodopa (450 mg/day) plus benserazide (112.5 mg/day) in 3 divided oral doses/day of Madopar modifies the ACTH/cortisol and/or the LH response to naloxone (4 mg as an i.v. bolus plus 10 mg infused in 2 hours). Ten parkinsonian patients (aged 52-62 years) and 8 normal controls (50-60 years) were tested with naloxone and in a different occasion with normal saline. The parkinsonian patients were tested both before and after dopaminergic treatment. Tests started at 09.00 h and lasted 2.5 hours. Basal ACTH/cortisol and LH levels were similar in all groups. During saline tests, ACTH/cortisol levels showed a slight physiological decline in all groups, whereas LH levels remained constant. Naloxone administration significantly increased the plasma levels of ACTH/cortisol and LH in the normal controls, but not in the parkinsonian patients before the dopaminergic treatment. In contrast, dopaminergic therapy restored significant ACTH/cortisol and LH responses to naloxone in parkinsonian patients. In fact, after levodopa plus benserazide, naloxone-induced ACTH, cortisol and LH increments in parkinsonian patients were significantly higher than before therapy and were indistinguishable from those observed in the normal controls. These data suggest that in men Parkinson's-related dopaminergic alterations may underlie the defective endogenous opioid control of ACTH/cortisol and LH secretion.
Subject(s)
Adrenocorticotropic Hormone/blood , Levodopa/therapeutic use , Luteinizing Hormone/blood , Naloxone/metabolism , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Humans , Male , Middle AgedABSTRACT
It is generally accepted that presenile Alzheimer's disease (AD) has faster progression and severer clinical manifestation than senile onset AD. Recently a relative left frontal hypoperfusion was only found in patients with presenile AD by using SPECT imaging. The aim of the present report was to ascertain whether the same conclusion could be drawn matching the population with respect to the severity of the cognitive profile and disease duration. Twenty subjects for each group were studied with SPECT and no differences emerged between groups. It is postulated that presenile and senile onset AD represent aspects of the same biological process.
Subject(s)
Alzheimer Disease/diagnostic imaging , Age of Onset , Aged , Alzheimer Disease/epidemiology , Alzheimer Disease/psychology , Basal Ganglia/diagnostic imaging , Cerebral Ventricles/diagnostic imaging , Cerebrovascular Circulation/physiology , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Tomography, Emission-Computed, Single-PhotonABSTRACT
In order to test possible changes in the stimulating effect of intravenously-infused substance P (SP) on ACTH/cortisol and GH secretion in Parkinson's disease, 10 male parkinsonian patients and 10 age-matched normal controls were infused intravenously for 60 min with SP (1.0 or 1.5 pmol/kg-1/min-1 SP) or normal saline. The circulating levels of ACTH, cortisol and GH were measured during and for 20 min after SP or saline infusion. No untoward side effects or changes in blood pressure were observed during SP infusion in any subjects. In basal conditions and during saline infusion, plasma ACTH and cortisol levels were similar in normal and parkinsonian patients. During SP infusions, ACTH/cortisol concentrations in normal controls rose significantly vs baseline and saline test in a dose-dependent fashion. In contrast, at both SP infused amounts, parkinsonian patients showed ACTH/cortisol levels similar to those observed in the saline test. All subjects showed similar basal concentrations of GH. GH levels rose significantly in the normal controls when the higher dose of SP was infused, but they were not modified by the infusion of the lower dose of SP or saline. At both tested amounts of SP and during saline infusion, GH levels remained unchanged in the parkinsonian subjects. In agreement with previous observations in the literature showing SP abnormalities in the parkinsonian brain, these data fail to show significant effects of plasma SP on the ACTH/cortisol and GH secretory systems in Parkinson's disease.
Subject(s)
Adrenocorticotropic Hormone/blood , Growth Hormone/blood , Hydrocortisone/blood , Parkinson Disease/blood , Substance P/pharmacology , Blood Pressure/drug effects , Dose-Response Relationship, Drug , Heart Rate/drug effects , Humans , Infusions, Intravenous , Male , Middle Aged , Prolactin/blood , Radioimmunoassay , Substance P/administration & dosage , Thyrotropin/bloodABSTRACT
In order to evaluate whether the stimulating effect of GABA on growth hormone (GH) secretion changes in patients affected by Parkinson's disease, ten male parkinsonian patients and ten age matched normal controls were tested with the GABA derivative and GABAergic agent Baclofen (10 mg in a single oral administration at 09.00 h) (experimental test). In a different occasion, normal men and parkinsonian patients were tested with a placebo (control test). Basal GH levels were similar in normal controls and parkinsonian patients and remained unmodified during the control test. Plasma GH levels rose three times within 120 min after the administration of baclofen in the normal subjects. In contrast, plasma GH concentrations remained unmodified after baclofen treatment in the parkinsonian patients. In agreement with previous reports in the literature showing alterations of GABAergic neurotransmission in the parkinsonian brain, these data show a reduced GABAergic control of GH secretion in patients with Parkinson's disease.
Subject(s)
Baclofen/pharmacology , Growth Hormone/metabolism , Parkinson Disease/metabolism , Aged , Growth Hormone/blood , Humans , Male , Middle Aged , Parkinson Disease/blood , Reference Values , gamma-Aminobutyric AcidABSTRACT
The Fuld formula and the linear discriminant function applied to WAIS subtest scores were tested for their ability to identify Alzheimer's disease and senile dementia of the Alzheimer type in a group of 101 demented subjects. The sensitivity and specificity of Fuld's formula for Alzheimer dementia against other dementias were 44.2% and 73.8% respectively; when compared with an age-matched normal control group specificity was 91.4%. When the linear discriminant function was applied only WAIS subtest scores in "similarities and digit span" and "object assembly" significantly differentiated Alzheimer from other dementias (sensitivity 61.5% and specificity 63.3%). Specificity increased to 97.1% when the function was applied to discriminate Alzheimer from normal controls. Discriminant analysis applied to other WAIS subtests for the two demented groups revealed "picture completion" as significantly differentiating the groups but it did not contribute to diagnostic accuracy. WAIS scores are of limited value in the differential diagnosis of dementias.
Subject(s)
Alzheimer Disease/diagnosis , Dementia/diagnosis , Wechsler Scales/statistics & numerical data , Aged , Diagnosis, Differential , Discriminant Analysis , Female , Humans , Male , Middle AgedABSTRACT
In order to establish whether the inhibitory control exerted by endogenous opioid peptides on ACTH/cortisol secretion changes in patients affected by Parkinson's disease, ten parkinsonian male subjects and eight age matched normal controls were tested with naloxone (4 mg an i.v. bolus plus 10 mg infused in two hours). In a different occasion all subjects were tested with normal saline. Experiments started at 09.00 h. Plasma ACTH and cortisol concentrations showed a slight physiological decline during saline test in both groups. In the normal controls and in the parkinsonian patients both ACTH and cortisol levels were significantly higher after naloxone administration than during saline test. However, both naloxone induced ACTH and cortisol responses were significantly higher in normal than in parkinsonian subjects. In agreement with the well-known opioid deficiency characterizing the parkinsonian brain, these data show a reduced opioid inhibitory control of ACTH/cortisol secretion in patients with Parkinson's disease.
Subject(s)
Adrenocorticotropic Hormone/metabolism , Hydrocortisone/metabolism , Naloxone , Parkinson Disease/blood , Adrenocorticotropic Hormone/blood , Aged , Humans , Hydrocortisone/blood , Kinetics , Male , Parkinson Disease/physiopathology , Reference Values , Time FactorsABSTRACT
Formal neuropsychological evaluation in patient with transient global amnesia (TGA) associated with migraine was performed 6 days and 17 months after the episode. Verbal learning difficulties and verbal IQ deficit were observed in line with the neuropsychological profile seen in the follow-up of TGA. A common origin for the TGA-Migraine episode and isolated TGA is discussed.
Subject(s)
Amnesia, Retrograde/etiology , Amnesia/etiology , Learning Disabilities/etiology , Migraine Disorders/complications , Amnesia, Retrograde/physiopathology , Female , Humans , Middle Aged , Migraine Disorders/physiopathology , Neuropsychological Tests , Time Factors , Verbal Learning/physiologyABSTRACT
A method for the relative quantification of 99mTc-HM-PAO distribution in brain SPECT is described. The method, applied in 12 normal volunteers and 150 patients suffering from different cerebral diseases, uses circumferential profiles to quantify the relative radionuclide distribution in the brain tomograms as an angular function with the origin at the center of the brain slice. Abnormal 99mTc-HM-PAO distribution is evaluated by comparing the count content of symmetrical selected parts of the profile curve and comparing each patient's profile with the corresponding limits of normal ones, determined from the pooled profiles of 12 normal subjects. This computerized method allows an accurate, reproducible and objective assessment of the relative HM-PAO distribution in the brain.
Subject(s)
Brain Diseases/diagnostic imaging , Cerebrovascular Circulation , Organometallic Compounds , Oximes , Tomography, Emission-Computed , Adult , Aged , Brain Diseases/physiopathology , Humans , Middle Aged , Technetium , Technetium Tc 99m ExametazimeABSTRACT
Description of a case of benign acute transverse myelopathy in a young woman who had taken heroin I.V. after a two-year free interval. Spinal angiography was negative but CT scanning of the cord showed a swelling at C3.