Familial aggregation in atypical Parkinson’s disease: a case control study in multiple system atrophy and progressive supranuclear palsy

Familial aggregation has been consistently found in PD, but it is unclear whether there is a familial aggregation in families of patients with multiple system atrophy (MSA) or progressive supranuclear palsy (PSP). MSA and PSP cases were recruited from a two-arm case control study. One control was matched to each case for age, gender and living area. Medical history of first-degree relatives was obtained through a face-to-face questionnaire. Age-specific cumulative incidence of Parkinsonism and dementia in first-degree relatives of cases and controls was compared for MSA and PSP separately. Seventy-one pairs for MSA and their controls and 79 pairs for PSP and their controls were included. No significant familial aggregation was found in PSP. MSA cases reported Parkinsonism more often, but not dementia in their first-degree relatives than controls. MSA patients, but not those with PSP, have Parkinsonism more often in their first-degree relatives than controls.     

Familial Parkinsonism and early onset Parkinson's disease in a Brazilian movement disorders clinic: Phenotypic characterization and frequency of SNCA,PRKN, PINK1, and LRRK2 mutations

The aim of the study was to evaluate the frequency and to perform phenotypic and genotypic characterization of familial Parkinsonism and early onset Parkinson's disease (EOPD) in a Brazilian movement disorder unit. We performed a standardized clinical assessment of patients followed by sequencing of PRKN, PINK1 in EOPD cases and SNCA, LRRK2 in familial Parkinsonism individuals. During the period of study (January through December, 2006), we examined 575 consecutive patients of whom 226 (39.3%) met the diagnosis of Parkinsonism and idiopathic Parkinson's disease (IPD) was diagnosed in 202 of the latter. Of the IPD cases, 45 (22.3%) had EOPD. The age at onset in the EOPD cases (n = 45) was 34.8 ± 5.4 years (mean ± standard deviation). The age at onset in the familial late‐onset PD patients (n = 8) was 52.3 ± 12.2 years. In the early onset cases, we identified five known mutations in PRKN, two single heterozygous and three compound heterozygous (P153R, T240M, 255Adel, W54R, V3I); in addition, we identified one novel mutation in PINK1 (homozygous deletion of exon 7). In the familial cases (late onset), 1 patient had a novel LRRK2 variant, Q923H, but no SNCA mutations were identified. We have demonstrated that EOPD accounts for a high frequency of IPD cases in our tertiary referral center. PRKN was the most commonly mutated gene, but we also identified a novel mutation in PINK1 and a novel variant in LRRK2. © 2009 Movement Disorder Society     

Does apolipoprotein E genotype modify the clinical expression of ALS?

Background: The presence of the apolipoprotein E (ApoE) 4 genotype is associated with an earlier age of onset for Alzheimer’s disease (AD) and several other neurodegenerative disorders. The objective of this study was to investigate the effect of ApoE genotypes on the clinical course of amyotrophic lateral sclerosis (ALS). Methods: Eight hundred and fifty‐two consecutive patients with sporadic ALS evaluated at a tertiary care center were investigated for the effect of ApoE genotype on age of onset, rate of motor disease progression, cognitive functioning, and survival in ALS. Results: The frequencies of individual ApoE genotypes did not differ between patients with ALS and ALS‐free Caucasian populations. Patients with different ApoE genotypes did not differ in the age of onset for ALS (years) (ApoE2 = 57.8 ± 13.7, ApoE3 = 57.3 ± 13.7, ApoE4 = 57.7 ± 13.2; P = 0.97), the rate of disease progression (Appel ALS score/month) (ApoE2 = 2.91 ± 2.66, ApoE3 = 2.67 ± 2.66, ApoE4 = 2.61 ± 2.47; P = 0.89), cognitive status (% cognitively impaired) (ApoE2 = 31.7, ApoE3 = 26.8, ApoE4 = 34.3, P = 0.28), or survival in years (ApoE2 = 3.79 ± 3.70, ApoE3 = 3.17 ± 2.27, ApoE4 = 3.05 ± 1.75; P = 0.85). Conclusions: Our results suggest that ApoE genotype does not modify clinical course of sporadic ALS, in stark contrast to the influence of ApoE genotype on the disease course of AD and other neurodegenerative disorders.     

Effects of paliperidone extended release on functioning level and symptoms of patients with recent onset schizophrenia: An open-label,single-arm,flexible-dose, 12-months follow-up study

Abstract

Background: Response to antipsychotic treatment is better in the early stages of schizophrenia. Aims: The primary objective of this non-randomized, single-arm, multicenter clinical trial was to explore the response to treatment and safety of a flexible dose of paliperidone (mean = 6.42 mg/day) in patients with recent onset schizophrenia (< 3 years after the first episode/hospitalization). Methods: Severity of clinical symptoms was evaluated by the Positive and Negative Syndrome Scale (PANSS), functioning was assessed using the Global Assessment of Functioning (GAF) scale and the Personal and Social Performance Scale (PSP). Results: In a total of 85 patients enrolled, 80 patients were eligible. Total PSP score at baseline (50.2 ± 11.6) increased at all visits. Total PSP score was 65.4 ± 12.1 at month 12 (P < 0.001). GAF scores were significantly higher at all visits compared with baseline (P = 0.001). It was 62.4 ± 12.5 with an increase of 42.9% at month 12 (P < 0.001). PANSS Positive and Negative subscales and General psychopathology subscale scores showed significant reductions beginning with month 3 and were 11.9 ± 3.8 (29.3%; P < 0.001), 13.7 ± 5.6 (27.3% P < 0.001) and 27.8 ± 7.1 (23.2%; P < 0.001) at month 12, respectively. Twelve patients (14.3%) had a serious adverse event. The most common adverse events were insomnia (17.9%), nausea (8.3%), akathisia (4.8%), anxiety (4.8%) and depression (4.8%). Body weight values at the end of the study were significantly higher compared with baseline. Conclusion: The present study demonstrates that flexible dose of paliperidone resulted in a significant improvement in functioning and reduction in symptoms in patients with recent onset schizophrenia.     

Substantia nigra echogenicity in progressive supranuclear palsy

A normoechogenic substantia nigra (SN) is a typical finding in transcranial sonography in patients with progressive supranuclear palsy (PSP), whereas in patients with Parkinson's disease a hyperechogenic SN is characteristic. A recent classification scheme recommends the differentiation of PSP patients into those with Richardson's syndrome (RS) and those with PSP‐Parkinsonism (PSP‐P). We investigated 34 PSP patients (27 RS, 7 PSP‐P) with ultrasound of the substantia nigra in search of differentiations in the two groups. We found that most of the PSP‐P patients, according to recently published criteria, had a hyperechogenic SN (6 of 7): right (cm²) median 0.22, 25% percentile 0.21 and 75% percentile 0.36 (cm²); left (cm²) median 0.21, 25% percentile 0.20 and 75% percentile 0.30 and a normal third ventricle (mean mm) ±SD: 7.1 ± 2.43). In RS patients a normoechogenic SN (26 of 27) and an enlarged third ventricle (mean mm) ±SD: 10.3 ± 2.41) was found. These differences may elucidate the pathological differences of RS and PSP‐P. © 2010 Movement Disorder Society     

Mild cognitive impairment with subcortical vascular features: clinical characteristics and outcome

Objectives: To identify non-demented individuals with cognitive impairment due to a cerebrovascular etiology among those coming to observation of a memory clinic and to describe their clinical features and outcome. Methods: Patients were enrolled in a prospective study on early cognitive impairment carried out in a Memory Clinic. Mild cognitive impairment of the vascular type (MCI-V) was defined based on modified criteria for subcortical vascular dementia (SVD) by Erkinjuntti and colleagues. Twenty-nine patients with MCI-V (age 78 ± 7, Mini Mental State Exam (MMSE) 24 ± 3) were compared with 14 with mild cognitive impairment of degenerative etiology (MCI) based on the Mayo Clinic criteria (age 72 ± 9, MMSE 25 ± 2), and to 21 patients with frank SVD (age 80 ± 6, MMSE 21 ± 3). Patients were followed over time for 32 ± 8 months. Results: MCI-V patients had a neuropsychological profile characterized by poor performance on frontal tests (Wisconsin card sorting and word fluency) and neurological features of parkinsonism without tremor (impairment of balance and gait). Of those followed for at least 40 months, 50 % of patients with MCI-V and SVD had died, while all MCI patients were still alive (P = 0.03). Of those alive, 68 % of the MCI-V, 52 % of the SVD, and 17 % of the MCI patients had reached one of the following outcomes at 40 months: nursing home placement, functional loss, and cognitive deterioration (P = 0.02). Conclusions: Patients with MCI-V have a distinctive clinical picture and can be identified in a clinical setting. Because of the high frequency of adverse outcomes, very early preventive measures need to be devised. Received: 27 July 2001, Received in revised form: 22 February 2002, Accepted: 22 April 2002 Correspondence to Giovanni B. Frisoni, MD     

Lower limb involvement in adult‐onset primary dystonia: frequency and clinical features

Background and purpose: Despite the growing number of reports describing adult‐onset primary lower limb dystonia (LLD) this entity has never been systematically evaluated in the general population of patients with primary adult‐onset dystonia. Methods: From outpatients with adult‐onset primary dystonia attending nine Italian University centres for movement disorders we consecutively recruited 579 patients to undergo a standardized clinical evaluation. Results: Of the 579 patients assessed, 11 (1.9%) (8 women, 3 men) had LLD, either alone (n = 4, 0.7%) or as part of a segmental/multifocal dystonia (n = 7, 1.2%). The age at onset of LLD (47.9 ± 17 years) was significantly lower than the age at onset of cranial dystonias (57.9 ± 10.7 years for blepharospasm, and 58.9 ± 11.8 years for oromandibular dystonia) but similar to that of all the other adult‐onset primary dystonias. The lower limb was either the site of dystonia onset (36.4%) or the site of dystonia spread (63.6%). In patients in whom LLD was a site of spread, dystonia seemed to spread following a somatotopic distribution. Only one patient reported a recent trauma involving the lower limb whereas 36.4% of the patients reported pain at the site of LLD. Only 64% of our patients needed treatment for LLD, and similarly to previously reported cases, the most frequently tried treatments was botulinum toxin and trihexyphenidyl. Conclusion: The lower limb is an uncommon but possible topographical site of dystonia in adulthood that should be kept in consideration during clinical evaluation.     

Risk factors for dementia, depression and psychosis in long-standing Parkinson's disease

Summary. Objectives. To study the relationships between clinical features of Parkinson's disease (PD) and the development of dementia, depression or psychosis in patients with long-standing disease. Background. The natural history of dementia and depression in PD, and its relation to psychosis in long standing PD, are unclear. Method. 172 consecutive patients (99 men and 73 women, mean age at symptoms onset 58.3 ± 13.2 years) with 5 years or more of PD (mean symptom duration of 11.8 ± 5.6 years) were studied. Clinical data were collected during the last office visit through physical examination, detailed history, review of patient charts and outside documents. Dementia and depression were diagnosed according to DSM-IV criteria, while psychosis was diagnosed if hallucinations or delusions were present. Chi-square and t tests were used to compare the patient characteristics among those with vs. those without mental complications of the disease at different disease stages. Logistic regression was used for the comparison of associations between the presence of dementia or depression (dependent variable) and age at onset of PD, duration of PD and disease staging (explanatory variables). Results. The study population consisted of 45 patients at Hoehn & Yahr (H&Y) stage ≤2.5 (26%), 104 patients at stage 3 (60.5%) and 23 patients at H&Y stage 4–5 (13.5%). Sixty one patients (36%) had dementia, 55 patients had depression (33%) and 50 patients (27%) had psychosis. Dementia and depression were significantly associated with disease severity as reflected in the H&Y scale (P = 0.0003, Z = 3.59; P = 0.006, Z = 3.22, respectively). These associations were significant also for the older age of PD onset (≥59 years n = 89) subgroup (p = 0.001, Z = 3.2 for dementia and p = 0.02, Z = 2.9 for depression), but not for younger onset cases (<59 years n = 83). Dementia was significantly associated with older age of PD onset (β = 0.04, p = 0.009) while depression was inversely associated with age of PD onset (β = −0.04, p = 0.02). The presence of dementia was also significantly associated with depression (β = 1.49, p = 0.0006). Dementia and depression were found to be independent explanatory variables for the development of psychosis (logistic regression, odds ratio (OR) = 26.0, p < 0.0001; OR = 10.2, p < 0.0001, respectively). In patients with younger age of PD onset, depression more than dementia was strongly correlated with the appearance of psychosis. Conclusion. Dementia in PD was related to older age of symptoms onset and old age. Depression was associated with dementia or early age of PD onset. Depression seemed to contribute to the appearance of psychosis even more than dementia, especially in patients with younger age of symptoms onset. Received January 28, 1999; accepted June 30, 1999     

The evolution of parkinsonism in primary progressive apraxia of speech: A 6-year longitudinal study

IntroductionPrimary progressive apraxia of speech (PPAOS) is a neurodegenerative syndrome in which patients present with an isolated motor speech disorder. Some PPAOS patients develop parkinsonism and other features of progressive supranuclear palsy (PSP) and/or corticobasal syndrome (CBS) over time. We aimed to assess the evolution of parkinsonian characteristics in PPAOS patients who had been followed yearly for at least six years.MethodsFrom a large cohort of 46 PPAOS patients, eight were followed yearly for > 6-years in multiple NIH-funded grants. Parkinsonian and other features, including bradykinesia, tremor, rigidity, postural instability, apraxia, ocular motor function and cognition were assessed at each visit, and research criteria applied for PSP and CBS diagnosis. Neurological, speech-language test scores, and [¹⁸F]fluorodeoxyglucose PET (FDG-PET) and MRI midbrain volumes were assessed.ResultsA Parkinson's plus syndrome developed in all eight patients (100%). Bradykinesia was the earliest feature, followed by rigidity and postural instability. Tremor was not a significant feature. Parkinsonism, limb apraxia and ocular motor impairment tended to develop four-to-five years after onset with some patients having slight asymmetric parkinsonism. Six patients (75%) met research criteria for probable PSP, although only one for PSP-Richardson's syndrome; three patients met criteria for possible CBS. Slightly asymmetric, left-sided, hypometabolism was observed on FDG-PET, not matching asymmetry of Parkinsonism. Midbrain hypometabolism was absent-minimal. Three patients had progressive midbrain volumes in the PSP-Richardson's syndrome range.ConclusionsA Parkinson's plus syndrome may inevitably develop in PPAOS supporting PPAOS as an early presentation of a Parkinson's plus disorder.     

The utility of FDG-PET in the differential diagnosis of Parkinsonism

Introduction: Differential diagnosis of parkinsonian disorders can be difficult on clinical grounds, especially in the early stage. Recent advancements in 18-F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging reveals different patterns of regional glucose metabolism in idiopathic Parkinson’s disease (IPD) and atypical parkinsonian syndromes, such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), which may help differentiating between these conditions.

Purpose: To assess the utility of FDG-PET imaging in differential diagnosis of Parkinsonism in clinical practice.

Methods: FDG-PET was performed in 72 patients with parkinsonism (age 34–80 years) referred to our center by movement disorder specialists. FDG-PET diagnosis was obtained by visual assessment of individual scans combined with voxel-based statistical parametric mapping analysis. FDG-PET diagnosis assigned at the time of imaging was compared with the final clinical diagnosis made by the movement disorder specialists after ≥2 years follow-up.

Results: FDG-PET findings were consistent with IPD in 27, MSA in 18, PSP in 19 and CBS in 2 patients. The final clinical diagnosis was IPD in 29, MSA in 20, PSP in 21 and CBS in 2 patients. Concordance between the FDG-PET and clinical diagnoses was 92% in the overall sample (IPD 93%, MSA 90%, PSP 91% and CBS 100%). The diagnostic accuracy of FDG-PET was 93% for IPD and MSA and 97% for PSP.

Conclusion: FDG-PET may help differentiate between IPD, MSA, PSP and CBS among patients presenting with parkinsonian symptoms, which is important for patient counselling and making early decisions about treatment.     

Cerebrospinal fluid tau and phosphorylated tau protein are elevated in corticobasal syndrome

Differentiating corticobasal syndrome (CBS) from progressive supranuclear palsy (PSP) and idiopathic Parkinson's disease (PD) can be difficult. To investigate the additional value of cerebrospinal fluid (CSF) biomarkers in the diagnostic differentiation of parkinsonism, we analyzed the CSF concentrations of total protein, lactate and brain specific proteins amyloid‐β₄₂ protein, tau protein (t‐tau), and tau protein phosphorylated at Thr181 (p‐tau), in CSF samples from patients with PSP (n = 21), CBS (n = 12), and PD (n = 28). CBS patients demonstrated higher concentrations of t‐tau and p‐tau compared with PSP and PD patients. In discriminating CBS and PD, t‐tau offered the best combination of sensitivity (75%) and specificity (90.9%), followed by p‐tau (sensitivity 87.5% and specificity 75%). The p‐tau/t‐tau ratio resulted in sensitivity of 84.2% and specificity of 66.7% in discriminating PSP and CBS. In conclusion, our results suggest that CSF parameters are of additional value in the diagnostic differentiation of CBS and PD. © 2010 Movement Disorder Society     

Progressive supranuclear palsy: earlier age of onset in patients with the τ protein A0/A0 genotype

Genetic studies have detected an association between the presence of the τ gene A0 allele and patients with progressive supranuclear palsy (PSP). This study examined whether patients with this polymorphism exhibit distinct demographic or clinical characteristics. We studied 26 patients who fulfilled clinical criteria for the diagnosis of PSP, 20 who had the A0/A0 genotype and 6 who had other genotypes. A questionnaire on demographic data, past medical history, familial history, and initial symptoms was completed as part of the consultation. A complete neurological examination was performed and PSP symptoms were quantified following Golbe’s PSP disability scale. We found a significant difference in the age at onset of PSP symptoms, which was 65.9 ± 5.3 years in the A0/A0 group and 71.2 ± 5.6 in the non-A0/A0 group (P = 0.016). There were no significant differences in the years from disease onset between the two groups. Symptom severity did not differ significantly in patients with the different A0/A0 genotypes. The detection of significantly lower age at onset with the A0/A0 alleles is consistent with the known association of this genotype as a risk factor for PSP. No significant differences were detected in symptom severity between the two groups of patients. Received: 5 May 1999/Received in revised form: 23 July 1999/Accepted: 17 November 1999     

Alpha‐synuclein polymorphisms are associated with Parkinson's disease in a Saskatchewan population

Alpha‐synuclein gene (SNCA) mutations cause familial Parkinsonism but the role of SNCA variability in idiopathic Parkinson's disease (PD) remains incompletely defined. We report a study of SNCA genetic variation in 452 idiopathic PD cases and 245 controls. SNCA copy number mutations were not associated with early‐onset disease in this population. The minor allele “G” at rs356165 was associated with increased odds of PD (P = 0.013) and genetic variation in D4S3481 (Rep1) was associated with age of disease onset (P = 0.007). There was a trend toward association between variation at rs2583988 and rapid PD progression. © 2009 Movement Disorder Society     

Differential pattern of brain‐specific CSF proteins tau and amyloid‐beta in Parkinsonian syndromes

To evaluate cerebrospinal fluid (CSF) proteins reflecting processes of neurodegeneration and glial activation in progressive supranuclear palsy (PSP; Richardson's syndrome, n = 20; PSP‐Parkinsonism, n = 7) and multiple system atrophy (MSA, n = 25), we analyzed tau, phosphorylated tau, amyloid‐beta_1–42 (Aβ1–42), Aβ1–40, glial fibrillary acidic protein (GFAP), and CSF routine variables. Individuals with PSP‐Parkinsonism and MSA had elevated tau levels when compared with Richardson's syndrome, Parkinson's disease (PD), and age‐matched controls (P ≤ 0.001). Ratios of P‐tau/T‐tau were significantly different in Parkinsonian syndromes. CSF Aβ1–42 was decreased only in patients with Richardson's syndrome. In a subset of Parkinsonian syndromes, we found elevated GFAP concentrations and increased CSF/serum albumin ratios. There were no correlations between biomarker concentrations and clinical scores in any of the diseases. In conclusion, this preliminary data show that changes in CSF tau and Aβ1–42 may indicate different protein processing in PSP patients and might, therefore, be relevant in the differentiation of PSP subtypes. © 2010 Movement Disorder Society     

Quantification of the heterogeneity of cerebral blood flow in vascular dementia

Background: In vascular dementia (VaD), assessment of cerebral blood flow by single photon emission computed tomography (CBF SPECT) has been used to detect a patchy decrease of blood flow or a frontal reduction. In addition to reduced blood flow, the heterogeneous distribution of cerebral blood flow is often observed in VaD. However, no objective method to evaluate the heterogeneity has been established. In this study, we applied three-dimensional fractal analysis (3D-FA) to CBF SPECT images as a method for assessing the heterogeneity of the cerebral blood flow distribution in VaD. Subjects and Methods: The subjects included 18 patients with a diagnosis of VaD (aged 69.7 ± 8.3) based on neuropsychological testing and imaging findings and 18 age-matched controls (aged 66.9 ± 10.3). CBF SPECT images were obtained with ^99mTc-hexamethyl propyleneamine oxime. On the reconstructed images, we obtained a linear regression equation between the cut-off values (from 35 to 50 %) and the number of voxels with a radioactivity exceeding the cut-off value transformed into natural logarithms, and then calculated the fractal dimension from the slope of the regression line thus obtained. The Mini-Mental State Examination (MMSE) was used to evaluate cognitive function. Results: The fractal dimensions were 1.084 ± 0.153 and 0.853 ± 0.062 (mean ± SD) in the VaD and control groups, respectively. The fractal dimension was significantly greater in the VaD group than in the control group (p < 0.0001). A significant negative correlation was observed between the fractal dimension and the MMSE score in the VaD group (r = 0.871, p < 0.0001). Conclusions: Because the CBF SPECT images of VaD patients showed a higher fractal dimension, these images were quantitatively more heterogeneous than those of age-matched controls. In the VaD group, cognitive function was shown to decline as the fractal dimension increased and images became more heterogeneous. Received: 20 June 2002, Received in revised form: 10 September 2002, Accepted: 16 September 2002 Correspondence to Takuya Yoshikawa, MD     

Haplotype analysis of the PARK 11 gene,GIGYF2, in sporadic Parkinson's disease

Familial Parkinsonism (PARK) genes are strong candidates for conferring susceptibility to common forms of PD. However, most studies to date have provided little evidence that their common variants substantially influence disease risk. Recently, mutations were described in the gene, GIGYF2 (TNRC15), located at the PARK11 locus (2q37.1). Here, we use a haplotype tagging approach to examine common variation in the GIGYF2 gene and PD risk. PD cases (n = 568) and age and gender‐matched control subjects (n = 568) were recruited from three specialist movement disorder clinics in Brisbane (Australia) and the Australian electoral roll. Twelve tagging SNPs were assessed in all subjects and haplotype and genotype associations were explored. Overall our findings suggest that common genetic variants of GIGYF2 do not significantly affect sporadic PD risk in Australian Caucasians. © 2008 Movement Disorder Society     

Alzheimer's disease and corticobasal degeneration presenting as corticobasal syndrome

The aim of this article is to compare patients with Alzheimer's disease (AD) pathology and corticobasal degeneration pathology (CBD) presenting as corticobasal syndrome (CBS). Clinicopathologic series was used. Five patients with AD and 11 patients with CBD were clinically diagnosed with CBS. Patients with AD pathology had an earlier age of onset than patients with CBD pathology (58 vs. 68 years, P = 0.004), but the two groups had similar disease duration and core features of CBS. Tremors were only present in CBD cases (73%, P = 0.026), but myoclonus was more common in AD than CBD (80 vs. 18%, P = 0.036). Neuropsychological testing showed similar degrees of memory impairment and attentional deficits. ^99mTc‐HMPAO SPECT imaging demonstrated parietal hypoperfusion in AD patients and frontotemporal hypoperfusion in CBD patients. AD patients with clinical CBS have similar characteristics to CBD patients. Functional brain imaging may have greater utility than the clinical and neuropsychological features in differentiating AD presenting as CBS from CBD. © 2009 Movement Disorder Society     

Dementia,walking outdoors and getting lost: incidence,risk factors and consequences from dementia-related police missing-person reports

Objectives: To estimate incidence, identify consequences and potential risk factors for harm in people with dementia who got lost in one UK policing region.

Methods: In a retrospective observational study, data were extracted from missing-person records over a four-year period in one UK policing region (population of 2.1 million).

Results: Two hundred and eighty-one incidents of getting lost were identified. Incidence of getting lost was estimated at 0.5% of the regional dementia population. Fifty-nine percent of reports came from domestic settings, 29% from care homes/hospitals, and 12% on excursions from home. Five percent (n = 15) sustained significant harm, including two deaths. Average age was 78 years (SD 8.3). Harm was associated with older age (mean difference 6.16 years, CI 1.86 to 10.46, p = 0.005, t = 2.82), length of time missing (Mdn time 2.48 hours; IQR 0.97 to 9.45, p = 0.02), and season (9% winter, 2% summer, p = 0.006). The length of time missing increased with delays in reporting to police (r = 0.15, p = 0.018), getting lost at night (Mdn time 1.70 hours, IQR 0.52–3.32, p = 0.028), driving themselves (Mdn time 2.45 hours, IQR 0.42–2.00, p = 0.001), and using public transport (Mdn 1.78 hours, IQR 1.07–3.92, p = 0.001).

Conclusion: Incidence in this study suggests getting lost is a low-frequency event for people with dementia but for a small minority, the risks are considerable. Exploratory analyses suggest individual and environmental factors increase the risk of harm. Suitable methods need to be developed to replicate these findings in larger prospective samples. A focus on the predictors of harm may aid development of assessment protocols to ensure intervention is proportionate.     

Obsessive compulsive personality disorder in Progressive Supranuclear Palsy,Multiple System Atrophy and Essential Tremor

Introductionaim of the study was to evaluate the presence of the Obsessive Compulsive Personality Disorder (OCPeD) in Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP) and Essential Tremor (ET) and in a group of healthy subjects.Methodspatients affected by MSA, PSP and ET diagnosed according to currently accepted diagnostic criteria and a group of healthy controls were enrolled in the study. Patients with cognitive impairment were excluded from the study. The Structured Clinical Interview for Personality Disorders-II (SCID-II) has been performed to evaluate the presence of personality disorders (PeDs). The diagnosis of OCPeD was confirmed by a psychiatric interview.Resultsfifteen MSA patients (8 men and 7 women; aged 62.9 ± 7.6 years), 14 PSP patients (8 men and 6 women; aged 69.8 ± 4.4 years), 16 ET patients (10 men and 6 women; aged 70.4 ± 6.4 years) and 20 healthy subjects (10 men and 10 women; aged 65.5 ± 6.0 years) were enrolled. OCPeD was recorded in 5 (35.7%) PSP patients, 2 (13.3%) MSA patients, 2 (12.5%) ET patient and 2 (10%) controls.Conclusiona low frequency of OCPeD, close to those recorded in healthy subjects, was recorded in both MSA and ET patients. Conversely an higher frequency of OCPeD, similar to PD was found among PSP patients, supporting the possibility of an impairment of common basal ganglia network possibly involving the orbito-frontal circuits.     

Apparent diffusion coefficient of the superior cerebellar peduncle differentiates progressive supranuclear palsy from Parkinson's disease

The early diagnosis of progressive supranuclear palsy (PSP) may be challenging, because of clinical overlapping features with Parkinson's disease (PD) and other parkinsonian syndromes such as the Parkinsonian variant of multiple system atrophy (MSA‐P). Conventional MRI can help in differentiating parkinsonian disorders but its diagnostic accuracy is still unsatisfactory. On the basis of the pathological demonstration of superior cerebellar peduncle (SCP) atrophy in patients with PSP, we assessed the SCP apparent diffusion coefficient (ADC) values in patients with PSP, PD, and MSA‐P in order to evaluate its differential diagnostic value in vivo. Twenty‐eight patients with PSP (14 with possible‐PSP and 14 with probable‐PSP), 15 PD, 15 MSA‐P, and 16 healthy subjects were studied by using diffusion weighted imaging (DWI). ADC was calculated in regions of interest defined in the left and right SCP by two clinically blinded operators. Intrarater (r = 0.98, P < 0.001) and interrater reliability (r = 0.97; P < 0.001) for SCP measurements were high. Patients with PSP had higher SCP rADC values (median 0.98 × 10^?3mm²/s) than patients with PD (median 0.79 × 10^?3 mm²/s, P < 0.001), MSA‐P (median 0.79 × 10^?3 mm²/s, P < 0.001), and healthy controls (median 0.80 × 10^?3 mm²/s, P < 0.001). DWI discriminated patients with PSP from PD and healthy subjects on the basis of SCP rADC individual values (100% sensitivity and specificity) and from patients with MSA‐P (96.4% sensitivity and 93.3% specificity). The higher values of rADC in SCP of patients with PSP correspond with the in vivo microstructural feature of atrophy detected postmortem and provide an additional support for early discrimination between PSP and other neurodegenerative parkinsonisms. © 2008 Movement Disorder Society