- Email: [email protected]
O.048 Mild cognitive impairment in patients with Parkinson's disease
Oral presentations / Parkinsonism and Related Disorders 15S2 (2009) S1–S28
a very small proportion of patients have a specific treatment (levodopa in dopa-responsive dystonia or drugs that prevent copper accumulation in Wilson’s disease). Therapeutic options must be tailored to the needs of individual patients: in focal dystonia, botulinum toxin is a safe and effective treatment (level I and II studies for blepharospasm and cervical dystonia) with a long term follow-up and a sustained beneficial effect. Physiotherapy could be added to botulinum toxin injections but a lot of debate has recently occurred on the available and future strategies. Most of them were based on pathophysiology of dystonia (altered sensorimotor integration, maladaptative plasticity, abnormal learning). Results of the available studies and new strategies will be discussed. In generalized or severe segmental dystonias, medical treatments should always be tried (anticholinergics, benzodiazepines) but deep brain stimulation (DBS) for patients with generalised dystonia demonstrated a dramatic effect. More recently, DBS has been offered as a therapeutic option in segmental and focal dystonia and indications, results and limitations will be discussed. A few secondary dystonia may benefit from DBS such as tardive dystonia and a sub-type of cerebral palsy but discussion will be expanded (from the medical point of view) to other types of genetic or metabolic disorders with dystonia. O.047 Dystonia: a surgeon’s point of view T. Aziz, A. Green. Nuffield Department of Surgery, University of Oxford, Oxford, UK Deep brain stimulation for the treatment of dystonia is now a well established therapy based upon numerous case series and a randomised control trial. As such, surgeons are increasingly requested by their neurological colleagues to undertake the treatment of such patients. From a surgeon’s point of view there are several important issues which will be discussed. Firstly is the dystonia primary or secondary. Data so far suggests that secondary dystonias do not respond as well as primary cases. It is clear now that the genetic phenotype no longer is a good predictor of outcome (e.g. DYT1). Physical findings that predict outcome seem to be onset of dystonia after a documented period of normality, short history, absence of fixed contractures, mobile dystonic movements and normal neuropsychological assessment. Secondly having established a good candidacy of a patient what surgery should be offered. So far the vast majority of patients have undergone deep brain stimulation of the medial pallidum with overall good effect. However there remain patients that still fail to respond adequately to surgery. The question as yet still unanswered is whether one emarked upon implanting further electrodes in the pallidum or target another site such as the subthalamic nucleus or thalamus. Finally what stimulation parameters should be used. Typically 130 Hz has been a uniform choice but studies indicate lower rates e.g. 60 Hz may be effective. These are all issues to be discussed. Parallel Session Cognitive changes and dementia in PD 10:45–12:15
December 15 Hall II
O.048 Mild cognitive impairment in patients with Parkinson’s disease C.H. Adler. Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA Cognitive decline in PD results in significant impairment and is a major predictor of nursing home placement and death. The estimates of dementia in PD range from 30% to >80%. Mild cognitive impairment (MCI) has been used to describe an intermediate stage between normal cognitive function and dementia but the majority of research published on MCI has been in the field of Alzheimer’s disease. Our group and others have reported patients with PD
S13
who have cognitive dysfunction but do not yet meet criteria for dementia. Applying MCI criteria to a population of subjects with PD, we have found three cognitive stages in 86 PD subjects: 53 (62%) cognitively normal, 18 (21%) PD-MCI, and 15 (17%) PD-D. In our longitudinal study of subjects enrolled for brain and body donation we have found that PD cases develop MCI at >6× the rate as non-PD subjects. Our program is also studying the pathologic substrate for MCI in PD, and findings suggest these cases may well have an intermediate stage of Lewy body and Alzheimer’s disease pathology. These and other topics related to MCI in patients with PD will be discussed. O.049 Functional and structural imaging of cognitive deficits in PD I. Rektorova. First Department of Neurology, Masaryk University and St. Anne’s Hospital, Brno, Czech Republic The incidence of dementia in Parkinson’s disease (PDD) is increased six-fold compared to the general population, and PD patients have cognitive deficits even in the absence of frank dementia. Structural imaging evaluates particularly the gray matter atrophy and aims at exploring the role of cortical neuronal loss in dementia and cognitive dysfunction and to study cortical atrophy in different neurodegenerative disorders with dementia. Voxel-based morphometry (VBM) has been used in particular. Functional imaging techniques (radiotracer imaging and activation studies using functional MRI [fMRI]) represent useful tools to assess in vivo the neurochemical alterations and functional connectivity in PD. PET and fMRI have demonstrated abnormal cortico-striatal function associated with cognitive deficits in PD. PET imaging with the b-amyloid-binding compound Pittsburgh Compound B (PiB) have shown that b-amyloid may contribute selectively to the cognitive impairment of PDD and other neurodegenerative dementias. In addition to activation studies, recent experiments suggest that cognitive performance also relies on the integrity of the default mode network [DMN] (i.e., medial prefrontal cortex, posterior cingulate cortex, precuneus, and lateral parietal and medial temporal cortices), characterized by a deactivation of these cortical areas during the performance of cognitive tasks. To date, most studies focused on the integrity of DMN in Alzheimer’s disease and amnestic type of mild cognitive impairment, but first results have been available als for PD. Recent studies dealing with both structural and functional imaging of cognitive deficits in PD and PDD will be reviewed. O.050 Management of dementia in Parkinson’s disease D. Burn. Newcastle University, Newcastle upon Tyne, UK The management of dementia in Parkinson’s disease (PD) is challenging, not least because of the frequency of the problem, but also that it invariably leads to therapeutic compromise. Thus, the treatment of psychosis or cognitive impairment may lead to some worsening of motor symptoms, and vice versa. Good management begins with a thorough assessment of the cognitive and neuropsychiatric features, preferably with validated instruments. After excluding intercurrent infections, subdural haematomas, severe depression, and other factors that may confound the diagnosis of dementia, the physician should draft a problem list of priorities. A small open trial has recently considered the use of a norepinephrine reuptake inhibitor, atomoxetine, in the management of executive dysfunction associated with PD. There was some evidence for benefit, although this was tempered by a number of adverse events, including hypomania in one case. Cholinesterase inhibitors may have a significant impact upon the cognitive and neuropsychiatric features in dementia associated with PD, although the response is somewhat variable. A large recent observational study in Canada has highlighted
a very small proportion of patients have a specific treatment (levodopa in dopa-responsive dystonia or drugs that prevent copper accumulation in Wilson’s disease). Therapeutic options must be tailored to the needs of individual patients: in focal dystonia, botulinum toxin is a safe and effective treatment (level I and II studies for blepharospasm and cervical dystonia) with a long term follow-up and a sustained beneficial effect. Physiotherapy could be added to botulinum toxin injections but a lot of debate has recently occurred on the available and future strategies. Most of them were based on pathophysiology of dystonia (altered sensorimotor integration, maladaptative plasticity, abnormal learning). Results of the available studies and new strategies will be discussed. In generalized or severe segmental dystonias, medical treatments should always be tried (anticholinergics, benzodiazepines) but deep brain stimulation (DBS) for patients with generalised dystonia demonstrated a dramatic effect. More recently, DBS has been offered as a therapeutic option in segmental and focal dystonia and indications, results and limitations will be discussed. A few secondary dystonia may benefit from DBS such as tardive dystonia and a sub-type of cerebral palsy but discussion will be expanded (from the medical point of view) to other types of genetic or metabolic disorders with dystonia. O.047 Dystonia: a surgeon’s point of view T. Aziz, A. Green. Nuffield Department of Surgery, University of Oxford, Oxford, UK Deep brain stimulation for the treatment of dystonia is now a well established therapy based upon numerous case series and a randomised control trial. As such, surgeons are increasingly requested by their neurological colleagues to undertake the treatment of such patients. From a surgeon’s point of view there are several important issues which will be discussed. Firstly is the dystonia primary or secondary. Data so far suggests that secondary dystonias do not respond as well as primary cases. It is clear now that the genetic phenotype no longer is a good predictor of outcome (e.g. DYT1). Physical findings that predict outcome seem to be onset of dystonia after a documented period of normality, short history, absence of fixed contractures, mobile dystonic movements and normal neuropsychological assessment. Secondly having established a good candidacy of a patient what surgery should be offered. So far the vast majority of patients have undergone deep brain stimulation of the medial pallidum with overall good effect. However there remain patients that still fail to respond adequately to surgery. The question as yet still unanswered is whether one emarked upon implanting further electrodes in the pallidum or target another site such as the subthalamic nucleus or thalamus. Finally what stimulation parameters should be used. Typically 130 Hz has been a uniform choice but studies indicate lower rates e.g. 60 Hz may be effective. These are all issues to be discussed. Parallel Session Cognitive changes and dementia in PD 10:45–12:15
December 15 Hall II
O.048 Mild cognitive impairment in patients with Parkinson’s disease C.H. Adler. Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA Cognitive decline in PD results in significant impairment and is a major predictor of nursing home placement and death. The estimates of dementia in PD range from 30% to >80%. Mild cognitive impairment (MCI) has been used to describe an intermediate stage between normal cognitive function and dementia but the majority of research published on MCI has been in the field of Alzheimer’s disease. Our group and others have reported patients with PD
S13
who have cognitive dysfunction but do not yet meet criteria for dementia. Applying MCI criteria to a population of subjects with PD, we have found three cognitive stages in 86 PD subjects: 53 (62%) cognitively normal, 18 (21%) PD-MCI, and 15 (17%) PD-D. In our longitudinal study of subjects enrolled for brain and body donation we have found that PD cases develop MCI at >6× the rate as non-PD subjects. Our program is also studying the pathologic substrate for MCI in PD, and findings suggest these cases may well have an intermediate stage of Lewy body and Alzheimer’s disease pathology. These and other topics related to MCI in patients with PD will be discussed. O.049 Functional and structural imaging of cognitive deficits in PD I. Rektorova. First Department of Neurology, Masaryk University and St. Anne’s Hospital, Brno, Czech Republic The incidence of dementia in Parkinson’s disease (PDD) is increased six-fold compared to the general population, and PD patients have cognitive deficits even in the absence of frank dementia. Structural imaging evaluates particularly the gray matter atrophy and aims at exploring the role of cortical neuronal loss in dementia and cognitive dysfunction and to study cortical atrophy in different neurodegenerative disorders with dementia. Voxel-based morphometry (VBM) has been used in particular. Functional imaging techniques (radiotracer imaging and activation studies using functional MRI [fMRI]) represent useful tools to assess in vivo the neurochemical alterations and functional connectivity in PD. PET and fMRI have demonstrated abnormal cortico-striatal function associated with cognitive deficits in PD. PET imaging with the b-amyloid-binding compound Pittsburgh Compound B (PiB) have shown that b-amyloid may contribute selectively to the cognitive impairment of PDD and other neurodegenerative dementias. In addition to activation studies, recent experiments suggest that cognitive performance also relies on the integrity of the default mode network [DMN] (i.e., medial prefrontal cortex, posterior cingulate cortex, precuneus, and lateral parietal and medial temporal cortices), characterized by a deactivation of these cortical areas during the performance of cognitive tasks. To date, most studies focused on the integrity of DMN in Alzheimer’s disease and amnestic type of mild cognitive impairment, but first results have been available als for PD. Recent studies dealing with both structural and functional imaging of cognitive deficits in PD and PDD will be reviewed. O.050 Management of dementia in Parkinson’s disease D. Burn. Newcastle University, Newcastle upon Tyne, UK The management of dementia in Parkinson’s disease (PD) is challenging, not least because of the frequency of the problem, but also that it invariably leads to therapeutic compromise. Thus, the treatment of psychosis or cognitive impairment may lead to some worsening of motor symptoms, and vice versa. Good management begins with a thorough assessment of the cognitive and neuropsychiatric features, preferably with validated instruments. After excluding intercurrent infections, subdural haematomas, severe depression, and other factors that may confound the diagnosis of dementia, the physician should draft a problem list of priorities. A small open trial has recently considered the use of a norepinephrine reuptake inhibitor, atomoxetine, in the management of executive dysfunction associated with PD. There was some evidence for benefit, although this was tempered by a number of adverse events, including hypomania in one case. Cholinesterase inhibitors may have a significant impact upon the cognitive and neuropsychiatric features in dementia associated with PD, although the response is somewhat variable. A large recent observational study in Canada has highlighted