Effects of a music therapy and music listening intervention for nursing home residents with dementia: a randomized controlled trial.

Introduction: The aim of the present study was to evaluate the effects of an individual music therapy intervention and an individual music listening intervention on neuropsychiatric symptoms and quality of life in people with dementia living in a nursing home and on professional caregiver's burden to be able to make statements about their specific value of application in clinical practice. Methods: A multicenter single blind randomized controlled trial with three groups was performed: an individual music therapy intervention (IMTI) group (n = 49), an individual music listening intervention (IMLI) group (n = 56) and a control group (n = 53) receiving usual care. The interventions were given during three weeks, three times a week on non-consecutive days during 30-45 minutes for in total nine sessions. The endpoint of the study is the difference from baseline to interim (1,5 week), post-intervention (3 weeks) and follow-up (6 weeks) in reported scores of problem behaviour (NPI-NH) and quality of life (Qualidem) in people with dementia and occupational disruptiveness (NPI-NH) in care professionals. Results: In total 158 people with dementia were randomized to one of the two intervention groups or the control group. Multilevel analyses demonstrated that hyperactive behaviour assessed by the NPI-NH was significantly more reduced for the IMLI group at follow up and that restless behaviour assessed by the Qualidem was significantly more reduced for the IMTI group at post and follow-up measurement compared to the control group. No significant effects between groups were found in other NPI-NH clusters or Qualidem subscales. Conclusion: In conclusion, because we found no convincing evidence that the IMTI or IMLI is more effective than the other both interventions should be considered in clinical practice. For the future, we advise further research into the sustainability of the effects with alternative designs, like a single case experimental design.

Sjögren-Larsson syndrome: The mild end of the phenotypic spectrum.

Sjögren-Larsson syndrome (SLS) is a rare inborn error of lipid metabolism. The syndrome is caused by mutations in the ALDH3A2 gene, resulting in a deficiency of fatty aldehyde dehydrogenase. Most patients have a clearly recognizable severe phenotype, with congenital ichthyosis, intellectual disability, and spastic diplegia. In this study, we describe two patients with a remarkably mild phenotype. In both patients, males with actual ages of 45 and 61 years, the diagnosis was only established at an adult age. Their skin had been moderately affected from childhood onward, and both men remained ambulant with mild spasticity of their legs. Cognitive development, as reflected by school performance and professional career, had been unremarkable. Magnetic resonance spectroscopy of the first patient was lacking the characteristic lipid peak. We performed a literature search to identify additional SLS patients with a mild phenotype. We compared the clinical, radiologic, and molecular features of the mildly affected patients with the classical phenotype. We found 10 cases in the literature with a molecular proven diagnosis and a mild phenotype. Neither a genotype-phenotype correlation nor an alternative explanation for the strikingly mild phenotypes was found. New biochemical techniques to study the underlying metabolic defect in SLS, like lipidomics, may in the future help to unravel the reasons for the exceptionally mild phenotypes. In the meantime, it is important to recognize these mildly affected patients to provide them with appropriate care and genetic counseling, and to increase our insights in the true disease spectrum of SLS.

The Diagnostic and Prognostic Value of Neuropsychological Assessment in Memory Clinic Patients.

BACKGROUND: Neuropsychological testing has long been embedded in daily clinical practice at memory clinics but the added value of a complete neuropsychological assessment (NPA) to standard clinical evaluation is unknown. OBJECTIVE: To evaluate the added diagnostic and prognostic value of NPA to clinical evaluation only in memory clinic patients. METHODS: In 221 memory clinic patients of a prospective cohort study, clinical experts diagnosed clinical syndrome (subjective cognitive impairment (SCI), mild cognitive impairment (MCI), or dementia) and etiology (Alzheimer's disease (AD) or no AD), and provided a prognosis of disease course (decline or no decline) before and after results of NPA were made available. The reference standard was a panel consensus based on all clinical information at baseline and up to 2 follow-up assessments. RESULTS: With NPA data available, clinicians changed their initial syndromal diagnosis in 22% of patients, and the etiological diagnosis as well as the prognosis in 15%. This led to an increase in correctly classified cases of 18% for syndromal diagnosis, 5% for etiological diagnosis, and 1% for prognosis. NPA data resulted in the largest improvement in patients initially classified as SCI (syndrome: 93.3% (n = 14) correctly reclassified, etiology: net reclassification improvement [NRI] = 0.61, prognosis: NRI = 0.13) or MCI (syndrome: 89.3% (n = 23) correctly reclassified, etiology: NRI = 0.17, prognosis: NRI = 0.14), while there was no improvement in patients with dementia (syndrome: 100% (n = 1) correctly reclassified, etiology: NRI = -0.05, prognosis: NRI = -0.06). Overall, inclusion of NPA in the diagnostic process increased confidence in all diagnoses with 6-7%. CONCLUSION: Administration of a complete NPA after standard clinical evaluation has added value for diagnosing cognitive syndrome and its underlying etiology in patients regarded as non-demented based on the first clinical impression.

Added Prognostic Value of Cerebrospinal Fluid Biomarkers in Predicting Decline in Memory Clinic Patients in a Prospective Cohort.

BACKGROUND: Limited information is available on short-term prognosis of Alzheimer's disease (AD) biomarkers in cerebrospinal fluid (CSF) in addition to routine diagnostic workup. OBJECTIVE: This study aims to investigate the added prognostic value of AD CSF biomarkers. METHODS: In a prospective cohort study, clinical experts predicted cognitive and functional symptoms in 114 memory clinic patients by assessing comprehensive routine diagnostic test information (patient history, and physical, neurological, psychiatric, neuropsychological, and MRI examinations), without and with CSF biomarkers. The reference standard was the 'observed clinically relevant decline' using baseline and 1- and 2-year follow-up information. RESULTS: Decline over a 2-year period was observed in 51% of all participants (3% in SMC, 48% in MCI, 90% in mild dementia). In the total sample, the accuracy of predicted decline did not differ significantly between routine assessment without (79% correctly predicted) and with (74% correctly predicted) CSF biomarkers. Subgroup analyses revealed 25 (83%) correct predictions in SMC, 30 (68%) in MCI, and 35 (88%) in dementia without the use of CSF; and 21 (70%), 27 (61%), and 36 (90%), respectively, with the use of CSF in addition to the routine assessment. CONCLUSION: AD CSF biomarkers did not increase accuracy of 2-year prognosis of cognitive and functional decline when added to routine diagnostic workup. This suggests that the standard diagnostic workup without CSF biomarkers allows fairly accurate predictions for the short-term course of symptoms. Routine AD biomarkers in CSF have limited prognostic value over 2 years in persons with a suspected cognitive disorder.

The role of the dopaminergic system in mood, motivation and cognition in Parkinson's disease: a double blind randomized placebo-controlled experimental challenge with pramipexole and methylphenidate.

In Parkinson's disease (PD) reduced dopaminergic activity in the mesocorticolimbic pathway is implied in the pathophysiology of several non-motor symptoms related to mood, motivation and cognition. Insight in the pathophysiology of these syndromes may pave the way for more rational treatments. In a double-blind, randomized, placebo controlled, crossover design with three arms, we studied the effects of a direct dopaminergic challenge with the dopamine 2 receptor agonist pramipexole, an indirect challenge with the dopamine reuptake inhibitor methylphenidate, and placebo on measures of mood, motivation and cognition in 23 agonist-naïve PD patients and 23 healthy controls. Acute challenge with pramipexole had a negative effect on mood and fatigue in both patients and controls. In addition, challenge with pramipexole led to increased anger, fatigue, vigor and tension in healthy control subjects, but not in PD patients. Challenge with methylphenidate had a positive effect on anhedonia and vigor in PD patients. Due to its side effects after a single administration, pramipexole is probably less suitable for acute challenge studies. The acute effects of a methylphenidate challenge on anhedonia and vigor in PD patients make this drug an interesting choice for further studies of the treatment of mood and motivational disorders in this population.

Deterioration of Parkinson's disease during hospitalization: survey of 684 patients.

BACKGROUND: A substantial fraction of Parkinson's disease patients deteriorate during hospitalisation, but the precise proportion and the reasons why have not been studied systematically and the focus has been on surgical wards and on Accident & Emergency departments. We assessed the prevalence and risk factors of deterioration of Parkinson's disease symptoms during hospitalization, including all wards. METHODS: We invited Parkinson's disease patients from three neurology departments in The Netherlands to answer a standardised questionnaire on general, disease and hospital related issues. Patients who had been hospitalized in the previous year were included and analysed. Possible risk factors for Parkinson's disease deterioration were identified. Proportions were analysed using the Chi-Square test and a logistic regression analysis was performed. RESULTS: Eighteen percent of 684 Parkinson's disease patients had been hospitalized at least once in the last year. Twenty-one percent experienced deterioration of motor symptoms, 33% did have one or more complications and 26% had received incorrect anti-Parkinson's medication. There were no statistically significant differences for these variables between admissions on neurologic or non-neurologic wards and between having surgery or not. Incorrect medication during hospitalization was significantly associated with higher risk (OR 5.8, CI 2.5-13.7) of deterioration, as were having infections (OR 6.7 CI 1.8-24.7). A higher levodopa equivalent dose per day was a significant risk factor for deterioration. When adjusting for different variables, wrong medication distribution was the most important risk factor for deterioration. CONCLUSIONS: Incorrect medication and infections are the important risk factors for deterioration of Parkinson's disease patients both for admissions with and without surgery and both for admissions on neurologic and non-neurologic wards. Measures should be taken to improve care and incorporated in guidelines.

Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy.

Cerebral amyloid angiopathy is caused by deposition of the amyloid beta protein in the cerebral vasculature. In analogy to previous observations in Alzheimer disease, we hypothesized that analysis of amyloid beta(40) and beta(42) proteins in the cerebrospinal fluid might serve as a molecular biomarker. We observed strongly decreased cerebrospinal fluid amyloid beta(40) (p < 0.01 vs controls or Alzheimer disease) and amyloid beta(42) concentrations (p < 0.001 vs controls and p < 0.05 vs Alzheimer disease) in cerebral amyloid angiopathy patients. The combination of amyloid beta(42) and total tau discriminated cerebral amyloid angiopathy from controls, with an area under the receiver operator curve of 0.98. Our data are consistent with neuropathological evidence that amyloid beta(40) as well as amyloid beta(42) protein are selectively trapped in the cerebral vasculature from interstitial fluid drainage pathways that otherwise transport amyloid beta proteins toward the cerebrospinal fluid.

MR imaging and proton MR spectroscopic studies in Sjögren-Larsson syndrome: characterization of the leukoencephalopathy.

BACKGROUND AND PURPOSE: Sjögren-Larsson syndrome (SLS) is a neurocutaneous syndrome caused by a genetic enzyme deficiency in lipid metabolism. Our purpose was to characterize the nature of the cerebral involvement in SLS. METHODS: MR imaging was performed in 18 patients (aged 5 months to 45 years) and repeated in 14. Single-voxel proton MR spectra were acquired from cerebral white matter and gray matter in 16 patients, with follow-up studies in 11. LCModel fits were used to determine brain metabolite levels. RESULTS: MR imaging showed retardation of myelination and a mild persistent myelin deficit. A zone of increased signal intensity was seen in the periventricular white matter on T2-weighted images. Proton MR spectroscopy of white matter revealed a prominent peak at 1.3 ppm, normal levels of N-acetylaspartate, and elevated levels of creatine (+14%), choline (+18%), and myo-inositol (+54%). MR imaging and proton MR spectroscopy of gray matter were normal. In the two patients examined during the first years of life, abnormalities on MR imaging and proton MR spectroscopy gradually emerged and then stabilized, as in all other patients. CONCLUSION: Abnormalities on MR imaging and proton MR spectroscopy emerge during the first years of life and are similar in all patients with SLS, but the severity varies. The changes are confined to cerebral white matter and suggest an accumulation of lipids, periventricular gliosis, delayed myelination, and a mild permanent myelin deficit.