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Biomedical subjects

H H Fernandez

Publications and source records attributed to H H Fernandez.

At least 19 recordsLinked to original sources

BDNF tagging polymorphisms and haplotype analysis in sporadic Parkinson's disease in diverse ethnic groups.

Experimental and clinical data suggest that genetic variations in brain-derived neurotrophic factor (BDNF) gene may affect risk for Parkinson's disease (PD). We performed a case-control association analysis of BDNF in three independent Caucasian cohorts (Greek, North American, and Finnish) of PD using eight tagging SNPs and five constructed haplotypes. No statistically significant differences in genotype and allele frequencies were found between cases and controls in all series. A relatively rare BDNF haplotype showed a trend towards association in the Greek (p=0.02) and the Finnish (p=0.03) series (this haplotype was not detected in the North American series). However, given the large number of comparisons these associations are considered non-significant. In conclusion, our results do not provide statistically significant evidence that common genetic variability in BDNF would associate with the risk for PD in the Caucasian populations studied here.

Aged↗

Limb-kinetic apraxia in Parkinson disease.

To learn if limb-kinetic apraxia (LKA) is associated with Parkinson disease (PD), participants with PD (on medications) and control subjects performed finger tapping (FT), measuring movement speed, and performed coin rotation (CR), measuring precise coordinated but independent finger movements and speed. There were no group differences in FT, a measure of bradykinesia-rigidity, but CR rotation was impaired in PD. Thus, LKA, not related to bradykinesia-rigidity, is associated with PD.

Aged↗

Dissociating apathy and depression in Parkinson disease.

OBJECTIVE: To examine the hypothesis that apathy is a core feature of Parkinson disease (PD) and that apathy can be dissociated from depression. METHODS: Eighty patients with PD and 20 patients with dystonia completed depression and apathy measures including the Marin Apathy Evaluation Scale (AES), Beck Depression Inventory (BDI), and Centers for Epidemiologic Studies-Depression Scale (CES-D). RESULTS: There was a significantly higher severity and frequency of apathy in PD (frequency = 51%, 41/80) than in dystonia (frequency = 20%, 4/20). Apathy in the absence of depression was frequent in PD and did not occur in dystonia (PD = 28.8%, dystonia = 0%). CONCLUSIONS: Patients with Parkinson disease (PD) experienced significantly higher frequency and severity of apathy when compared with patients with dystonia. Apathy may be a "core" feature of PD and occurs in the absence of depression.

Affective Symptoms↗

LRRK2 mutations in a clinic-based cohort of Parkinson's disease.

In the last decade, major breakthroughs in the understanding of genetic contributions to Parkinson's disease (PD) have been achieved. Recently, mutations in LRRK2, encoding dardarin, have been found to be responsible for an autosomal dominant parkinsonism (OMIM 607060). We screened 311 subjects (cases: n = 202, controls: n = 109) for the three previously reported LRRK2 mutations. Our investigation revealed a sporadic case of PD with a heterozygous mutation G2019S (c.6055G>A). Here, we present the clinical phenotype of this patient and discuss the implications of genetic testing for the G2019S mutation in patients with sporadic PD.

Adolescent↗

Donepezil for dementia in Parkinson's disease: a randomised, double blind, placebo controlled, crossover study.

OBJECTIVE: To study the safety and efficacy of a cholinesterase inhibitor, donepezil hydrochloride, for the treatment of dementia in Parkinson's disease (PD). METHODS: This was a randomised double blind, placebo controlled, crossover study in 22 subjects with PD and dementia. Participants were randomised to receive either donepezil followed by identical placebo, or placebo followed by donepezil. Donepezil was administered at 5-10 mg/day. Treatment periods were 10 weeks with a washout period of 6 weeks between the two periods. The primary outcome measure was the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAScog). RESULTS: Donepezil was well tolerated and most adverse events were mild. There was no worsening of PD symptoms as measured by the total or motor sections of the Unified Parkinson's Disease Rating Scale.There was a 1.9 point trend toward better scores on the ADAScog on treatment compared with placebo that was not statistically significant. The secondary cognitive measures showed a statistically significant 2 point benefit on the Mini Mental Status Examination and no change on the Mattis Dementia Rating Scale (MDRS). The Clinical Global Impression of Change (CGI) showed a significant 0.37 point improvement on donepezil. No improvement was observed on the MDRS or the Brief Psychiatric Rating Scale. Carryover between treatment periods was observed but was not statistically significant. CONCLUSIONS: Donepezil was well tolerated and did not worsen PD. There may be a modest benefit on aspects of cognitive function. The possible clinical benefit measured by CGI was reflected in only one of the cognitive scales used in this study.

Aged↗

Development and initial validation of a screening tool for Parkinson disease surgical candidates.

As there is currently no standardized assessment tool for evaluating Parkinson disease (PD) patients for deep brain stimulation (DBS), the authors developed the Florida Surgical Questionnaire for Parkinson Disease (FLASQ-PD). Part I of the study was a retrospective analysis of 174 patients presenting for a surgical screening. Part II was a multicenter study to assess the correlation of FLASQ-PD scores. The results of this study suggest that the FLASQ-PD may be a useful triage tool for screening PD patients for DBS surgery.

Deep Brain Stimulation↗

The course of tardive dyskinesia and parkinsonism in psychiatric inpatients: 14-year follow-up.

Tardive dyskinesia and parkinsonism were assessed in 53 patients residing in a state psychiatric hospital in 1984 and 1998. A 4.0-point decrease in the mean Abnormal Involuntary Movement Scale score (6.0 versus 2.0; p < 0.001) and a 3.5-point increase in the Rating Scale for Extrapyramidal Signs score (2.8 versus 6.3; p < 0.001) were noted between 1984 and 1998. Over a 14-year period, tardive dyskinesia improved and parkinsonism worsened in patients who continued to receive neuroleptic drugs.

Adult↗

Predictors of depressive symptoms among spouse caregivers in Parkinson's disease.

The objective of this work was to determine the predictors of depressive symptoms among spouse caregivers of Parkinson's disease (PD) patients. Little is known about the strain in giving care to PD patients and how the motor, cognitive, and behavioral complications of PD contribute to depression among spouse caregivers. Forty-five consecutive PD patients and their spouse caregivers agreed to be evaluated after a routine clinic visit. Patient demographic data and the presence of hallucinations, delusions, incontinence, and sleep disturbances were obtained. The patients were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS-motor section), Hoehn and Yahr (H&Y) staging, and the Mini-Mental State Examination (MMSE). Depressive symptoms were assessed using the 17-item Hamilton Depression Scale (HAMD-17) and the Beck Depression Inventory-II (BDI-II) on patients and spouses. Thirty men and 15 women had a mean age of 71.5 years (range 53-85), average PD duration of 10 years (range 1-26), a mean "on" H&Y stage of 2.8 and an MMSE mean score of 26 (range 13-30). There was good correlation between the HAMD-17 and the BDI-II scores in both patients (r = 0.69, P = 0.001) and spouses (r = 0.66, P < 0.001). A moderate correlation was noted between the spouse HAMD-17 score and the patient UPDRS-motor score (r = 0.34; P = 0.02), the age of PD onset (r = 0.33; P = 0.02) and patient HAMD-17 scores (r= 0.29; P = 0.05). A stronger correlation was noted between spouse HAMD-17 scores and the years of PD duration (r= 0.43; P = 0.003). There was a significant difference in the mean spouse HAMD-17 scores among PD patients with sleep disturbances versus those who did not (10.2 vs. 6.4; P = 0.04). However, on stepwise regression analysis, only the duration of PD remained significant (adjusted r = 0.17; P = 0.003). No difference was noted with hallucinations, delusions or incontinence. We concluded that the duration of PD appears to be the strongest predictor of depressive symptoms among spouse-caregivers in this small cohort.

Aged↗

Estrogen use among nursing home residents with a diagnosis of Parkinson's disease.

BACKGROUND: The role of estrogen in motor, cognitive, and behavioral functions in Parkinson's disease (PD) remains unclear. OBJECTIVES/METHODS: To determine differences in functional, cognitive, and behavioral patterns between estrogen users and non-users, we performed an observational study on 10,145 elderly women with PD using the Systematic Assessment in Geriatric drug use via Epidemiology (SAGE) database. The SAGE database consists of the Minimum Data Set (MDS), data collected on a cross-section of over 400,000 nursing home (NH) residents in five US states. Using a cross-sectional study design, we evaluated the demographics, physical and cognitive function, and mortality rates of women with PD who received estrogen (n = 195) versus those who did not receive estrogen (n = 9950). RESULTS: Independent of age, estrogen users were less cognitively impaired and more independent in their activities of daily living. Surprisingly, more estrogen users were depressed and more likely to be on an antidepressant than non-users. One-year death rates were comparable between estrogen users and non-users. CONCLUSION: This study supports the growing number of recent data suggesting estrogen's potential beneficial effects on PD motor and cognitive functions.

Activities of Daily Living↗

Variable absorption of carbidopa affects both peripheral and central levodopa metabolism.

Carbidopa (CD), a competitive inhibitor of aromatic l-amino acid decarboxylase that does not cross the blood-brain barrier, is routinely administered with levodopa (LD) to patients with Parkinson disease (PD) to reduce the peripheral decarboxylation of LD to dopamine. Using a stable isotope-labeled form of LD, the authors examined in 9 PD patients the effects of variable CD absorption on peripheral and central LD metabolism. Subjects were administered orally 50 mg of CD followed in 1 hour by a slow bolus intravenous infusion of 150 mg stable isotope-labeled LD (ring 1',2',3',4',5',6'-13C). Eight patients underwent a lumbar puncture 6 hours following the infusion. Blood and cerebrospinal fluid (CSF) samples were analyzed for labeled and unlabeled metabolites using a combination of high-performance liquid chromatography and mass spectrometry. When patients were divided into "slow" and "rapid" CD absorption groups, significantly greater peripheral LD decarboxylation (as measured by area under the curve [AUC]-labeled serum HVA) was noted in the poor absorbers (p = 0.05, Mann-Whitney U test). Elimination half-lives for serum LD did not differ between groups, suggesting a further capacity for decarboxylation inhibition in the "rapid" absorbers. A significant correlation between AUC serum CD and percent-labeled HVA in CSF was found for all patients (R = 0.786, p = 0.02). "Rapid" as compared to "slow" CD absorbers had significantly more percent-labeled CSF HVA (60 vs. 49, p = 0.02, Mann-Whitney U test), indicating greater central-labeled DA production in the better CD absorbers. The data suggest that peripheral aromatic l-amino acid decarboxylase activity is not saturated at CD doses used in current practice. The authors believe that future studies to better examine a dose dependence of CD on peripheral LD decarboxylation and LD brain uptake are warranted.

Absorption↗

Quetiapine for hypnogogic musical release hallucinations.

Musical release hallucinations are complex auditory phenomena, affecting mostly the deaf geriatric population, in which individuals hear vocal or instrumental music. Progressive hearing loss from otosclerosis disrupts the usual external sensory stimuli necessary to inhibit the emergence of memory traces within the brain, thereby "releasing" previously recorded perceptions. Responses to conventional antipsychotic agents have been variable and extrapyramidal and other side effects have limited their use. We report the first case of hypnogogic release hallucinations successfully treated with the atypical antipsychotic quetiapine. The patient is an 88-year-old woman with progressive deafness who complained of hearing the piano, drums, or a full orchestra every time she was about to fall asleep. She accused her neighbor of hosting loud parties. Physical, neurologic, and psychiatric examination and work-up were unremarkable. She was treated with low-dose quetiapine affording near total resolution of hallucinations without adverse effects.

Aged↗