Serum heme oxygenase‐1 levels are increased in Parkinson’s disease but not in Alzheimer’s disease

Mateo I, Infante J, Sánchez‐Juan P, García‐Gorostiaga I, Rodríguez‐Rodríguez E, Vázquez‐Higuera JL, Berciano J, Combarros O. Serum heme oxygenase‐1 levels are increased in Parkinson’s disease but not in Alzheimer’s disease.
Acta Neurol Scand: 2010: 121: 136–138.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – Oxidative stress is implicated in Parkinson’s disease (PD) and Alzheimer’s disease (AD), and heme oxygenase‐1 (HO‐1) is a potent antioxidant overexpressed in PD substantia nigra and AD cerebral cortex and hippocampus, indicating a possible up‐regulation of antioxidant defenses in both neurodegenerative diseases. The role of HO‐1 in peripheral blood of PD and AD patients remains unresolved. Methods – We measured serum HO‐1 levels in 107 patients with PD, 105 patients with AD, 104 controls for PD and 120 controls for AD. Results – The median serum concentration of HO‐1 was significantly higher in PD patients (2.04 ng/ml) compared with that of PD controls (1.69 ng/ml, P = 0.016), with PD patients predominating over controls in the upper tertile of serum HO‐1 levels, whereas there was more PD controls than PD patients in the lower tertile (P = 0.006). Median serum levels of HO‐1 did not differ significantly between AD patients and AD controls. Conclusion – The increase of serum HO‐1 levels in PD patients could indicate a systemic antioxidant reaction related to a chronic oxidative stress state in PD brain.     

Recurrent falls and mortality in Parkinson’s disease: a prospective two‐year follow‐up study

Matinolli M, Korpelainen JT, Sotaniemi KA, Myllylä VV, Korpelainen R. Recurrent falls and mortality in Parkinson’s disease: a prospective two‐year follow‐up study.
Acta Neurol Scand: 2011: 123: 193–200.
© 2010 John Wiley & Sons A/S. Objectives – To evaluate the risk factors for recurrent falling and mortality in Parkinson’s disease (PD) in a prospective study design. Materials and methods – One hundred and twenty‐five PD patients were included in the study. Baseline medical data were collected, and patients were clinically tested for mobility and balance. Falls were prospectively recorded for 2 years. Mortality was documented 4 years after the baseline. Results – Seventy‐nine patients reported altogether 3125 falls during the follow‐up, and 59 patients were classified as recurrent fallers. Altogether 126 fall injuries including six fractures were reported. Eighteen patients had died by the time of the hospital chart review. History of falling (OR 3.02, 95% CI 1.23–7.44) and the Unified Parkinson’s Disease Rating Scale activities of daily living score (OR 1.13, 95% CI 1.04–1.22) were independent risk factors for recurrent falling in PD, whereas slow walking speed (OR 16.28, 95% CI 1.85–142.97) was an independent risk factor for mortality in PD. Conclusions – History of falling and disease severity indicate increased risk of recurrent falls in PD, while patients with slow walking speed may have an increased risk of mortality. Recurrent falling was not associated with increased risk of mortality in PD in this study.     

Computerized cognition assessment during acetylcholinesterase inhibitor treatment in Alzheimer’s disease

Wesnes K, Edgar C, Andreasen N, Annas P, Basun H, Lannfelt L, Zetterberg H, Blennow K, Minthon L. Computerized cognition assessment during acetylcholinesterase inhibitor treatment in Alzheimer’s disease.
Acta Neurol Scand: 2010: 122: 270–277.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – Alzheimer’s disease assessment scale‐cognitive subscale (ADAS‐Cog) has become a standard clinical trials outcome for cognition, but has been recognized as deficient in areas including coverage of cognitive domains, sensitivity and standardization. Computerized test batteries may address some of these issues. The cognitive drug research computerized assessment (CDR) system is validated in Alzheimer’s disease (AD). This study was designed to further evaluate validity in relation to ADAS‐Cog, mini mental state examination (MMSE) and cerebrospinal fluid (CSF) biomarkers and psychometric properties, in a population of Alzheimer’s patients on stable anticholinesterase treatment. Materials and methods – Patients completed cognition assessments, CSF and blood sampling at baseline and 6 months later. Data for 65 patients were evaluated. Results – The CDR system demonstrated good psychometric properties in this population. Measures of psychomotor speed showed possible sensitivity to decline over 6 months. Conclusions – There are a number of methodological problems with current cognition assessment methodology for clinical trials. Computerized measures and in particular millisecond reaction time measures, may address many of these issues.     

Galantamine and behavior in Alzheimer disease: analysis of four trials

Kavanagh S, Gaudig M, Van Baelen B, Adami M, Delgado A, Guzman C, Jedenius E, Schäuble B. Galantamine and behavior in Alzheimer disease: analysis of four trials.
Acta Neurol Scand: 2011: 124: 302–308.
© 2011 John Wiley & Sons A/S. Objectives – Many individuals with Alzheimer’s disease (AD) experience behavioral and neuropsychiatric symptoms, which may cause caregiver distress and lead to the institutionalization of the patient. This analysis characterized behavioral symptoms and caregiver distress in trials of galantamine and their response to treatment. Materials and methods – Data were pooled from four randomized, placebo‐controlled clinical trials of galantamine in patients with mild to moderate AD (three studies) or AD plus cerebrovascular disease (one study) (n = 2177). Behavior and associated caregiver distress were assessed in each study using the Neuropsychiatric Inventory (NPI) and NPI distress (NPI‐D), respectively. Results – After 5/6 months, but not after 3 months, NPI score was significantly improved with galantamine vs placebo (P = 0.013). The benefit was particularly pronounced in patients categorized as having advanced moderate AD. At 5/6 months, there was a numerical benefit of galantamine over placebo in terms of caregiver distress; the difference was statistically significant in patients with moderate or advanced moderate AD. Conclusions – Galantamine reduces behavioral symptoms in patients with mild to moderate AD, leading to reduced caregiver burden. The reductions were greatest in patients with moderate or advanced moderate disease.     

Inclusion body myositis in Alzheimer's disease

Roos PM, Vesterberg O, Nordberg M. Inclusion body myositis in Alzheimer’s disease.
Acta Neurol Scand: 2011: 124: 215–217.
© 2010 John Wiley & Sons A/S. Background – The prevalence of Alzheimer’s disease is increasing. Could findings of similar deposits in brain and muscle tissue explain this increase? The purpose of this report is to illustrate that Alzheimer’s disease and inclusion body myositis may share a common aetiology. Results – We present a case where Alzheimer’s disease and inclusion body myositis coexist in the same patient. Amyloid‐beta deposition and the presence of phosphorylated tau protein have been noted in brain tissue and in muscle biopsy from patients with these disorders. Methods – Electrophysiological methods are needed for proper diagnosis of this brain and muscle disorder. Recent data on deposit structures in both conditions may indicate an environmental aetiology for Alzheimer’s disease and inclusion body myositis. Conclusion – By combining electrophysiological methods with muscle biopsy in cases of Alzheimer’s disease, the possible aetiological connection between simultaneous affection of both muscle and brain in this condition can be established.     

Activities of daily living and quality of life in persons with newly diagnosed Parkinson’s disease according to subtype of disease,and in comparison to healthy controls

Hariz G‐M, Forsgren L. Activities of daily living and quality of life in persons with newly diagnosed Parkinson’s disease according to subtype of disease, and in comparison to healthy controls.
Acta Neurol Scand: 2011: 123: 20–27.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objective – To describe activity of daily living (ADL) and quality of life (QoL) at first visit to a neurological centre, in patients subsequently diagnosed with Parkinson’s disease (PD), according to subtype of disease and compared to healthy controls. Materials and methods – 99 patients and 31 controls were included. Patients were classified into three groups according to predominant symptoms: 50 Postural instability‐gait difficulties (PIGD), 37 tremor dominant, 12 indeterminate. Evaluations included ADL‐taxonomy, SF‐36, and the Parkinson disease questionnaire (PDQ‐39). Results – Patients experienced early on limitations in ADL and QoL compared to controls. Patients with PIGD subtype had already at first visit a worse status, clinically and in ADL and QoL, than patients with tremor dominant type. Conclusions – Already at first visit to a neurological centre, patients who will eventually receive the diagnosis of PD exhibited restrictions in ADL and QoL. Patients with axial symptoms were affected most.     

Serum somatostatin in early‐stage Parkinson’s disease

Shiraishi M, Kobayashi T, Watanabe H, Kamo T, Hasegawa Y. Serum somatostatin in early‐stage Parkinson’s disease.
Acta Neurol Scand: 2010: 121: 225–229.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – To compare levels of plasma digestive hormones in patients with and without nausea or vomiting during initial treatment of early‐stage Parkinson’s disease (PD). Methods – This was a 3‐week, open‐label, randomized study of treatment with an antiparkinson drug in untreated PD patients. We measured the levels of plasma digestive hormones before (baseline) and 3 weeks after administration of an antiparkinson drug. Results – Mean value of serum somatostatin at baseline was significantly increased in PD patients compared with the control group (P < 0.01). Serum somatostatin levels were significantly increased after treatment in subjects who experienced nausea or vomiting (P < 0.01). However, significant increase in serum somatostatin levels after treatment was not observed in PD patients without nausea or vomitting. Conclusion – Serum somatostatin in early‐stage PD patients before treatment was increased compared with healthy subjects. The nausea and vomiting induced by antiparkinson drugs may be related to uncontrolled somatostatin secretion through central vagus nerve dysfunction .     

Tetranectin and apolipoprotein A‐I in cerebrospinal fluid as potential biomarkers for Parkinson’s disease

Wang E‐S, Sun Y, Guo J‐G, Gao X, Hu J‐W, Zhou L, Hu J, Jiang C‐C. Tetranectin and apolipoprotein A‐I in cerebrospinal fluid as potential biomarkers for Parkinson’s disease.
Acta Neurol Scand: 2010: 122: 350–359.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objective – The application of biomarkers may potentially improve the efficiency of the diagnosis for Parkinson’s disease (PD). However, no reliable biomarker has been identified to date. This study is aimed to identify proteins that might serve as potential biomarkers for PD diagnosis or pathogenesis. Materials and methods – Two‐dimensional difference gel electrophoresis (2D DIGE) technique, in combination with matrix‐assisted laser desorption/ionization‐time of flight mass spectrometry (MALDI‐TOF MS), was used to determine the differentially expressed cerebrospinal fluid (CSF) proteins in PD patients (n = 3) compared with normal controls (n = 3). Selected proteins were further confirmed by Western blotting analysis in the CSF of PD patients (n = 8), Alzheimer’s disease (AD) patients (n = 6) and normal control subjects (n = 7). Results – Eight proteins were identified after MS and protein database interrogation. In the CSF of PD patients, the expression levels of one isoform of apolipoprotein A‐I (apoA‐I), tetranectin, myosin phosphatase target subunit 1 (MYPT1), and two unknown proteins were down‐regulated, whereas the expression levels of another apoA‐I isoform, proapolipoprotein, and lipoprotein were up‐regulated. Western blotting indicates that the expression of tetranectin was reduced in the CSF from PD patients and elevated in AD, while the expression of apoA‐I was changed only in the CSF from PD patients. Conclusion – Our preliminary results suggest that tetranectin and apoA‐I may serve as potential biomarkers for PD, though further validation is needed.     

Medication dose reductions after pallidal versus subthalamic stimulation in patients with Parkinson's disease

Evidente VGH, Premkumar AP, Adler CH, Caviness JN, Driver‐Dunckley E, Lyons MK. Medication dose reductions after pallidal versus subthalamic stimulation in patients with Parkinson’s disease.
Acta Neurol Scand: 2011: 124: 211–214.
© 2010 John Wiley & Sons A/S. Objective – To compare the medication dose reduction between deep brain stimulation (DBS) of the globus pallidus interna (GPi) vs subthalamic nucleus (STN) in matched patients with Parkinson’s disease (PD). Materials and methods – Records of 12 patients with PD who underwent GPi‐DBS at our institution from 2002 to 2008 were matched by pre‐operative PD medication doses and pre‐operative motor Unified Parkinson’s Disease Rating Scale (UPDRS) scores to 12 cases of STN‐DBS. PD medication doses were converted to levodopa equivalent doses (LEDs). Results – GPi and STN groups had similar mean pre‐operative LEDs and motor UPDRS scores. At 6 months post‐DBS, there was no significant difference in percent reduction in LEDs between the GPi (47.95%) and STN (37.47%) groups (P = 0.52). The mean post‐operative ‘medication off/stimulation on’ motor UPDRS scores did not differ significantly between GPi (15.33) and STN (16.25) groups (P = 0.74). The mean percent reduction in motor UPDRS scores was also similar between GPi (58.44%) and STN (58.98%) patients (P = 0.94). Conclusions – We conclude that in disease‐matched patients with PD undergoing DBS, both GPi and STN may result in similar reduction in PD medication doses.     

Death‐associated protein kinase 1 variation and Parkinson’s disease

Background and purpose: Mutations of the LRRK2 gene are now recognized as major risk factors for Parkinson’s disease. The Lrrk2 protein is a member of the ROCO family, which also includes Lrrk1 and Dapk1. Functional genetic variants of the DAPK1 gene (rs4877365 and rs4878104) have been previously associated with Alzheimer’s disease. Methods: Herein, we assessed the role of DAPK1 variants (rs4877365 and rs4878104) in risk of Parkinson’s disease with Sequenom iPLEX genotyping, employing one Taiwanese series (391 patients with Parkinson’s disease, 344 controls) and five separate Caucasian series’ (combined sample size 1962 Parkinson’s disease patients, 1900 controls). Results: We observed no evidence of association for rs4877365 and rs4878104 and risk of Parkinson’s disease in any of the individual series or in the combined Caucasian series under either an additive or recessive model. Conclusion: These specific DAPK1 intronic variants do not increase the risk of Parkinson’s disease. However, further functional studies are required to elucidate the potential therapeutic implications with the dimerization of the Dapk1 and Lrrk2 proteins.     

Heart rate variability in Parkinson's disease unaffected by deep brain stimulation

Trachani E, Constantoyannis C, Sakellaropoulos GC, Stavrinou ML, Nikiforidis G, Chroni E. Heart rate variability in Parkinson’s disease unaffected by deep brain stimulation.
Acta Neurol Scand: 2012: 126: 56–61.
© 2011 John Wiley & Sons A/S. Objectives – Our aim was to investigate the impact of subthalamic nucleus deep brain stimulation (STN‐DBS) on the cardiovagal control of patients with advanced Parkinson’s disease. Materials and methods – Twenty‐four patients (mean age: 62.1 ± 9.4 years) were examined 3 days before and 6 months after DBS by a questionnaire, blood pressure monitoring and a battery of neurophysiological tests: time domain analysis of RR interval variation during normal and deep breathing (DB), Valsalva manoeuvre, and tilt test. By off‐line, performed frequency domain analysis of heart rate variation, total power (TP), low frequency band (LF) band, high‐frequency (HF) band, and their normalized units were estimated. The neurophysiological measurements were compared to those of 24 healthy controls. Results – The values of time domain variables were pre‐ and postoperatively lower in patients than in controls. A significant reduction was found in LF band after the implantation. Orthostatic hypotension was present in 45.8% of the patients preoperatively and 12.5% postoperatively. There was no correlation between DBS‐related changes of motor function and corresponding neurophysiological measurements, but patients with more than 60% motor improvement had higher time domain parameters’ values than the others. Conclusions – STN‐DBS offered no considerable impact on autonomic cardiovascular control.     

Drug and treatment costs in Parkinson's disease patients in Sweden

Lökk J, Borg S, Svensson J, Persson U, Ljunggren G. Drug and treatment costs in Parkinson’s disease patients in Sweden.
Acta Neurol Scand: 2012: 125: 142–147.
© 2011 John Wiley & Sons A/S. Background – Parkinson’s disease (PD) is a chronic neurodegenerative disease expected to cause great costs. The aim of this study was to calculate drug and treatment costs in patients with PD in Sweden. Method – All healthcare contacts of patients with PD in Stockholm County, Sweden, were extracted from registers together with information on reimbursements from the authorities to the caregivers. PD‐related costs were calculated together with non‐PD‐related costs. Cost per patient was calculated and extrapolated to the whole Swedish population, taking population demographics into consideration. In addition, nationwide PD drug sales statistics were included. Results – The PD prevalence of Stockholm County was estimated to 196 per 100,000 inhabitants, resulting in an estimated total of about 22,000 patients with PD in Sweden. The cost per patient was estimated to SEK 76,000 of which drug costs accounted for SEK 15,880. The annual direct costs in patients with PD in Sweden were SEK 1.7 billion in 2009. Conclusion – Our study estimates high direct costs in patients with PD in Sweden, SEK 1.7 billion, 52% for inpatient care, 27% for outpatient care and 21% for drugs. With an ageing population and the medical progress, the financial burden on society will most probably increase in the future. This study might initiate and provide information for discussions about future cost allocations and healthcare priorities.     

Caregiver distress associated with neuropsychiatric problems in patients with early Parkinson’s disease: the Norwegian ParkWest study

Leiknes I, Tysnes O‐B, Aarsland D, Larsen JP. Caregiver distress associated with neuropsychiatric problems in patients with early Parkinson’s disease: the Norwegian ParkWest study.
Acta Neurol Scand: 2010: 122: 418–424.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives – We investigated caregiver distress associated with neuropsychiatric problems in patients with newly diagnosed Parkinson’s disease (PD). Materials and methods – Persons who were next of kins of 198 patients and 168 healthy individuals completed the Neuropsychiatric Inventory Caregiver Distress Scale. Results – Even at the time of diagnosis PD has a considerable impact on the next of kins’ experience of distress. Nearly 50% reported distress, significantly more than in the control group, and more than one‐quarter reported moderate severe distress. Except the more rarely reported neuropsychiatric symptoms, apathy was the symptom that most frequently caused caregiver distress in PD patient’s next of kin (94.5%), followed by depression (88.2%), anxiety (86.2%) and irritability (83.3%). Conclusions – The study underlines the importance of focusing on neuropsychiatric aspects in patients and associated caregiver distress even in early PD management.     

Leptin and ghrelin concentrations and weight loss in Parkinson’s disease

Fiszer U, Micha?owska M, Baranowska B, Wolińska‐Witort E, Jeske W, Jethon M, Pia?cik‐Gromada M, Marcinowska‐Suchowierska E. Leptin and ghrelin concentrations and weight loss in Parkinson’s disease.
Acta Neurol Scand: 2010: 121: 230–236.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – To investigate the role of leptin, ghrelin, GH and IGF‐1 in energy balance disturbances in Parkinson’s disease (PD). Materials and methods – Thirty‐nine patients were included: 11 PD patients with unintentional weight loss, 16 PD patients without weight loss and 12 controls. UPDRS, MMSE, MADRS, appetite scale, BMI, adipose tissue content, plasma leptin and active ghrelin concentrations and serum GH, IGF‐1, TSH, T3 and T4, concentrations were evaluated. Results – A lower plasma leptin concentration and a higher serum IGF‐1 concentration were found in PD patients with weight loss. BMI and the content of adipose tissue were positively correlated with leptin concentration in all PD patients. Paradoxically, the lower BMI was, the lower plasma active ghrelin concentration was in PD patients with the weight loss. Conclusion – These findings confirm that changes of plasma leptin concentration occur in PD patients with loss of weight.     

The stability of AQT processing speed,ADAS‐Cog and MMSE during acetylcholinesterase inhibitor treatment in Alzheimer’s disease

Wiig EH, Annas P, Basun H, Andreasen N, Lannfelt L, Zetterberg H, Blennow K, Minthon L. The stability of AQT processing speed, ADAS‐Cog and MMSE during acetylcholinesterase inhibitor treatment in Alzheimer’s disease.
Acta Neurol Scand: 2010: 121: 186–193.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objectives – To explore the longitudinal stability of measures of cognition during treatment with acetylcholinesterase inhibitors (AchEI) in patients with Alzheimer’s disease (AD). Materials and methods – Cognitive status was measured in a cohort of 60 patients at 6 months after initiation of treatment with AchEI (baseline) and after an additional 6 months of treatment (endpoint). A Quick Test of Cognitive Speed (AQT), Alzheimer’s Disease Assessment Scale‐Cognitive Subscale (ADAS‐Cog), and MMSE were administered concurrently. Results – Correlations (ρ) between age and AQT processing speed were non‐significant, but were significant for ADAS‐Cog and Mini Mental State Examination (MMSE). AQT and ADAS‐Cog means did not differ significantly between baseline and endpoint. There was a small, significant reduction in MMSE point scores. Measures of stability (Spearman’s ρ) were moderate‐to‐high for all tests. Means for subgroups did not differ as a function of medication type. Conclusions – AQT processing speed, ADAS‐Cog, and MMSE measures proved stable during the second 6 months of treatment with AChEI.     

Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson's disease

Constantinescu R, Holmberg B, Rosengren L, Corneliusson O, Johnels B, Zetterberg H. Light subunit of neurofilament triplet protein in the cerebrospinal fluid after subthalamic nucleus stimulation for Parkinson’s disease.
Acta Neurol Scand: 2011: 124: 206–210.
© 2010 John Wiley & Sons A/S. Objectives – Cerebrospinal fluid (CSF) levels of neurofilament triplet protein (NFL), a non‐specific marker of neuronal damage, are normal in Parkinson’s disease (PD) but increased after brain trauma and in several neurological disorders. Using longitudinal CSF‐NFL measurements as an indicator of neuronal damage, this study investigated the impact of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the brain, directly following the surgical intervention and in chronically treated patients with PD. Materials and methods – CSF‐NFL levels were measured consecutively in eight patients with PD before and after STN‐DBS treatment. Results – CSF‐NFL levels were normal prior to STN‐DBS and increased sharply during the first 2 weeks post‐operatively, but normalized after 12 months or more. Conclusion – The STN‐DBS procedure leads to an acute but limited neuronal damage, as expected. However, normal CSF‐NFL levels at 12 months post‐operatively and beyond suggest the absence of any long‐term neuronal damage caused by long‐term STN‐DBS stimulation.     

Prevalence of Parkinson's disease and atypical parkinsonian syndromes in a rural Japanese district

Osaki Y, Morita Y, Kuwahara T, Miyano I, Doi Y. Prevalence of Parkinson’s disease and atypical parkinsonian syndromes in a rural Japanese district.
Acta Neurol Scand: 2011: 124: 182–187.
© 2010 John Wiley & Sons A/S. Objectives – To investigate the prevalence of Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS) in a rural Japanese district. Method – Collaboration with the medical institutions, the long‐term care insurance system facilities, and the public health office. Results – The crude prevalence rates were 175 per 100 000 (95% CI: 143–206) for PD, 18 (8–28) for progressive supranuclear palsy, 17 (7–26) for multiple system atrophy (MSA), and 9 (2–16) for corticobasal degeneration. The age‐adjusted prevalence rates were 109 per 100 000 (88–134), 10 (2–17), 13 (4–21), and 6 (0–12), for each condition. There was a preponderance of women with PD and of men with APS. Nine of the 116 PD patients and 7 of the 29 APS patients were newly diagnosed in this study. Conclusions – There are high prevalence rates for PD and APS and suboptimal recognition of APS. This is the first epidemiological prevalence study of MSA from Japan.     

CERAD-neuropsychological battery in screening mild Alzheimer's disease

Sotaniemi M, Pulliainen V, Hokkanen L, Pirttilä T, Hallikainen I, Soininen H, Hänninen T. CERAD‐neuropsychological battery in screening mild Alzheimer’s disease.
Acta Neurol Scand: 2012: 125: 16–23.
© 2011 John Wiley & Sons A/S. Objectives – The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery (nb) is used as an evaluation tool for dementia. In Finland, CERAD‐nb was introduced in 1999 and has been proposed to be used in primary health care. However, some of its parts need reassessment and focusing. The goal of this study was to examine the sensitivity and specificity of the subtests and their cut‐off points most appropriate for identifying mild Alzheimer’s disease (AD). Materials and Methods – The study population consisted of 171 patients with mild AD and 315 cognitively normal elderly. Both groups underwent CERAD‐nb investigation as a part of a wider examination procedure. Results – The most efficient subtests to discriminate patients with mild AD from the normal elderly were Wordlist delayed recall and savings, Wordlist learning and Wordlist recognition and a new variable of Total recall. Optimal cut‐off points for each subtest are suggested. The sensitivities of the verbal memory subtests varied between 0.75 and 0.94, the specificities between 0.80 and 0.93 and the areas under the receiver operating characteristics curve between 0.89 and 0.96. Conclusions – The CERAD‐nb is capable of differentiating cases with mild AD from normal elderly individuals particularly with its verbal memory subtests. New cut‐off scores for CERAD’s subtests validated in the study further enhance the differentiating power, and with these clarifications, CERAD‐nb is considered appropriate to be used as a screening tool for AD even in primary health care.     

The role of APOE alleles in incident Parkinson’s disease. The Norwegian ParkWest Study

Vefring H, Haugarvoll K, Tysnes O‐B, Larsen JP, Kurz MW, for the Norwegian ParkWest Study group. The role of APOE alleles in incident Parkinson’s disease. The Norwegian ParkWest Study.
Acta Neurol Scand: 2010: 122: 438–441.
© 2010 John Wiley & Sons A/S. Objectives – Apolipoprotein E (APOE) gene alleles have been associated with various neurodegenerative disorders. However, there have been conflicting reports on associations between APOE alleles and Parkinson’s disease (PD) and age at onset in PD. There exist no data on APOE alleles in an unselected cohort of patients with incident PD. Patients and methods – To determine the role of APOE alleles in PD and age of onset in PD at time of diagnosis, 203 patients with incident PD and 187 healthy control subjects from Western and Southern Norway were investigated according to their APOE allele status. Results – No association was observed between any APOE alleles and susceptibility to PD or age at onset in PD. Conclusion – In our cohort of unselected, incident PD patients APOE alleles do not seem to play a role for development of PD. Prospective, long‐term follow‐up may still reveal associations between APOE alleles and clinical and neuropsychological progression in PD.     

Two galantamine titration regimens in patients switched from donepezil

Engedal K, Davis B, Richarz U, Han J, Schäuble B, Andreasen N. Two galantamine titration regimens in patients switched from donepezil.
Acta Neurol Scand: 2012: 126: 37–44.
© 2011 John Wiley & Sons A/S. Objectives – In addition to inhibiting acetylcholinesterase, galantamine has allosteric‐modulating activity at nicotinic receptors. This may make galantamine an attractive option for patients starting treatment for Alzheimer’s disease (AD), but also for those who have not benefited from their current therapy. This study explored outcomes in subjects with AD transitioning from donepezil because of insufficient tolerability or efficacy. Materials and methods – Subjects previously receiving donepezil for mild‐to‐moderate AD were enrolled in a 12‐week randomized, open‐label study. After screening and a 7‐day washout, subjects were randomly allocated to galantamine fast (8 mg/week increments) or slow (8 mg/4 week) titration to 16–24 mg. Efficacy outcomes included the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS‐cog/11), Mini‐Mental State Examination (MMSE), Clinician’s Interview‐Based Impression of Change – Plus Caregiver’s Input (CIBIC‐plus) and Alzheimer’s Disease Cooperative Study – Activities of Daily Living Inventory (ADCS‐ADL). Results – Eighty‐six of 89 patients (fast titration, n = 44; slow titration, n = 45) completed the study. At week 12, ADAS‐cog/11 score improved from screening by 2.6 and 0.6 in the fast‐ and slow‐titration arms, respectively (overall, ?1.6; P = 0.002). MMSE scores improved slightly in both arms (overall, +0.9; P = 0.002). Two‐thirds of patients had improvement or no change on the CIBIC‐plus at week 12. ADCS‐ADL scores did not change significantly from screening in either treatment arm. Galantamine was generally well tolerated; nausea (5.6%) and bradycardia (4.5%) were the most commonly reported adverse events. Conclusions – Patients in whom donepezil is ineffective or poorly tolerated may benefit from a switch to galantamine.