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Comparison of apraxia severity of dementia syndromes
Presentation P4 test. A 2X2 full factorial design (SPM8) (group: carrier vs. non-carrier, by task level: 0-relational, 1-relational, 2-relational) was used to compare activation in carriers and non-carriers, with post-hoc contrast p < 0.05 applied to compare intermediate complexity (0- vs. 1-relational) and high complexity (1- vs. 2-relational) within each group separately. Results: Behaviorally, carriers performed less well than non-carriers across all conditions (accuracy: 0-relational 89.2 vs. 98.9% p ¼ 0.005, 1-relational 72.9 vs. 97.9% p ¼ 0.03, 2-relational 45.8 vs. 65.6%, p ¼ 0.0005; speed: 0-relational 3.92s vs. 3.43s p ¼ 0.56, 1-relational 5.09 vs. 4.15s p ¼ 0.015, 2-relational 6.93 vs. 6.07s p ¼ 0.00002). fMRI post-hoc contrast 0- vs. 1-relational showed significantly increased activation of posterior cingulate in carriers without a similar pattern in non-carriers. By contrast, fMRI post-hoc contrast 1- vs. 2-relational showed no change in carriers regardless of response accuracy, but significantly increased activation in anterior cerebellar areas was found in non-carriers. Conclusions: GRN mutation carriers respond to increasing complexity in matrix reasoning differently than non-carriers in their clinical performance as well as in their fMRI brain activation pattern. Carriers appear to significantly recruit posterior brain regions and have declining performance at intermediate complexity, but no change at high complexity. This may suggest a posteriorly located compensatory mechanism in carriers that is functional up to a certain level only, but breaks down with further increases in matrix complexity.
P4-181
DEMENTIA IN PAKISTAN: INITIAL RESULTS FROM OUR REGISTRY AT A TERTIARY CARE HOSPITAL
Arsalan Ahmad, Ismail Khatri, Maimoona Siddiqui, Nilofer Khan, Sascha Kamal, Nadia Mehboob, Shifa International Hospital, Islamabad, Pakistan, Islamabad, Pakistan. Background: The number of people with dementia in Asia is expected to double every 20 years and by 2050; Asia will have the largest population of dementia patients in the world. Geriatric diseases are on the rise in Pakistan probably due to increasing life expectancy. We established the first dementia registry in Pakistan and present results of the first 60 patients from our dementia registry. Methods: All patients with dementia coming for neurology consultation from October 1, 2010 to January 15, 2011 were included for analysis. Demographic and clinical data was recorded on the registry proforma and included identification data, clinical history and examination, pertinent investigations and cognitive assessment tools: Mini Mental State Examination (MMSE), Neuro Psychological Inventory (NPI), Beck Depression Inventory (BDI) and Beck Anxiety Inventory. Data were analysed using Statistical Package for the Social Sciences (SPSS) version 16. Results: Out of 60 patients, 55% were male. The mean age was 70.5 years with a range of 47-99 years. 80% were married and 20% widowed. 40% were graduates or postgraduates. 81.7% presented with memory loss as the chief complaint. 20% had a prior history of stroke, 36.7% had parkinsonism, 41.7% had hypertension, 33.3 % had diabetes mellitus and only 28.3% were smokers. A family history of dementia was obtained in 35%. Primary clinical diagnosis was probable Alzheimer’s disease in 28.3%, Parkinson’s disease dementia in 25%, vascular dementia in 8.3%. MRI was done in 48.3% and CT scan head was done in 45% of patients. 26.7% were on donepezil, 20% on rivastigmine, 18.3% on memantine, 16.7% on galantamine whereas 6.7% patients were on a combination of two drugs. Conclusions: Our initial clinical data, risk factors, epidemiology and pattern of dementia is similar to the rest of the world. Larger studies are needed, and this can be done by establishing registries so that we are ready to face the increasing demand of dementia care in our region.
P4-182
COMPARISON OF APRAXIA SEVERITY OF DEMENTIA SYNDROMES
€ Demet Ozbabalik, Eskisehir Osmangazi University Nese Tuncer 2, Didem Arslantas, Neurology 1, Public Healthy 3 Marmara University Neurology, Eskisenir, Turkey.
S767
Background: Apraxia is defined as difficulty performing learned and commonly seen in neurodegenerative condition characterized by frontal, parietal, and basal ganglia disease. Aim to assess severity of apraxia in dementia syndromes. Methods: Eight hundred and ten dementia patients were evaluated for apraxia severity through a clinical database program. All results were compared to type of dementia, MMSE and clinical dementia rating. Results: While there is positive correlation between apraxia scores and Mini-Mental Status Examination (MMSE) (r ¼ 0.67, p < 0.0001), there is negative correlation between apraxia and clinical dementia rating (r ¼ 0.67, p < 0.001). Apraxia was seen more severe amongst degenerative dementias including Alzheimer’s, Frontotemporal dementia, Lewy body dementia and Parkinson (r ¼ 0.57, p < 0.001). Vascular dementia was second order frequency (r ¼ 0.48 p < 0.001). Conclusions: Apraxia is observed frequencely amongst dementia syndromes. The severity and frequency of apraxia is due to severity and involvement of syndromes. Thus cortical degenerative causes are more responsible for apraxia than vascular causes.
P4-183
PRION
Simon Mead, MRC Prion Unit, London, United Kingdom. Background: Prion diseases are rare fatal neurodegenerative disorders associated with aggregates of misfolded prion protein. There are several parallels with Alzheimer’s disease including clinical features, molecular mechanisms and neuropathology. The natural history and early signs associated with human prion diseases have not been well defined. There are no validated progression scales or biomarkers for use in a clinical trial setting. Methods: At the UK NHS National Prion Clinic we have systematically assessed and followed up around 350 patients in clinical trial-like or observational cohort studies to help solve these problems. The protocol and enrollment criteria allow for recruitment of patients at risk of disease due to exposure to possibly prion-infected blood or through prion protein gene mutation in order to capture the presymptomatic and earliest clinical stages of disease. Results: We report the assessment of 8 rating methodologies and development of a bespoke composite rating scale for progression based on completion rates, validity and performance in simulated clinical trials. This new MRC scale is composed of a modification of questions derived from the Barthel ADL, the Glasgow Coma Scale and the Clinicians Dementia Rating scale. We show that the scale is suitable for use over the telephone, allowing for documentation of rapid clinical decline at a distance. As part of this work we have performed more than 120 quantitative MRI scans allowing for the development of imaging biomarkers. We are also evaluating the role of a blood test for abnormal prion protein. Conclusions: We describe an ongoing study which may be used as an example of one way to tackle the problem of clinical research in a rare dementia. The development of rating scales and biomarkers in prion disease have parallels and distinctions from Alzheimer’s disease.
P4-184
PROFILE OF SELECTIVE ORL1 ANTAGONIST DEMONSTRATES MECHANISM SAFE TO TARGET FOR SYMPTOMATIC TREATMENT IN ALZHEIMER’S DISEASE
Allen Duplantier, Rathna Iyer, Betty Pettersen, Robin Roof, Julie Cianfrogna, Louis Leung, Michael Brodney, Laura McDowell, Jason Barricklow, Keri Cannon, Cheng Chang, Claire Leurent, Faith Prior, Christine Taylor, Todd Wisialowski, Pfizer Global Research and Development, Groton, Connecticut, United States. Background: Antagonism of the ORL1 receptor has been proposed as a novel mechanism of action to treat Alzheimer’s disease (AD) associated cognitive symptoms. Challenges to the discovery of ORL1 antagonists include selectivity against the m, k and d opioid receptors and retention of ORL1 potency, while modulating the physicochemical properties to achieve low oral dosing and brain availability. From the safety and tolerability perspectives, identifying a selective ORL1 antagonist
P4-181
DEMENTIA IN PAKISTAN: INITIAL RESULTS FROM OUR REGISTRY AT A TERTIARY CARE HOSPITAL
Arsalan Ahmad, Ismail Khatri, Maimoona Siddiqui, Nilofer Khan, Sascha Kamal, Nadia Mehboob, Shifa International Hospital, Islamabad, Pakistan, Islamabad, Pakistan. Background: The number of people with dementia in Asia is expected to double every 20 years and by 2050; Asia will have the largest population of dementia patients in the world. Geriatric diseases are on the rise in Pakistan probably due to increasing life expectancy. We established the first dementia registry in Pakistan and present results of the first 60 patients from our dementia registry. Methods: All patients with dementia coming for neurology consultation from October 1, 2010 to January 15, 2011 were included for analysis. Demographic and clinical data was recorded on the registry proforma and included identification data, clinical history and examination, pertinent investigations and cognitive assessment tools: Mini Mental State Examination (MMSE), Neuro Psychological Inventory (NPI), Beck Depression Inventory (BDI) and Beck Anxiety Inventory. Data were analysed using Statistical Package for the Social Sciences (SPSS) version 16. Results: Out of 60 patients, 55% were male. The mean age was 70.5 years with a range of 47-99 years. 80% were married and 20% widowed. 40% were graduates or postgraduates. 81.7% presented with memory loss as the chief complaint. 20% had a prior history of stroke, 36.7% had parkinsonism, 41.7% had hypertension, 33.3 % had diabetes mellitus and only 28.3% were smokers. A family history of dementia was obtained in 35%. Primary clinical diagnosis was probable Alzheimer’s disease in 28.3%, Parkinson’s disease dementia in 25%, vascular dementia in 8.3%. MRI was done in 48.3% and CT scan head was done in 45% of patients. 26.7% were on donepezil, 20% on rivastigmine, 18.3% on memantine, 16.7% on galantamine whereas 6.7% patients were on a combination of two drugs. Conclusions: Our initial clinical data, risk factors, epidemiology and pattern of dementia is similar to the rest of the world. Larger studies are needed, and this can be done by establishing registries so that we are ready to face the increasing demand of dementia care in our region.
P4-182
COMPARISON OF APRAXIA SEVERITY OF DEMENTIA SYNDROMES
€ Demet Ozbabalik, Eskisehir Osmangazi University Nese Tuncer 2, Didem Arslantas, Neurology 1, Public Healthy 3 Marmara University Neurology, Eskisenir, Turkey.
S767
Background: Apraxia is defined as difficulty performing learned and commonly seen in neurodegenerative condition characterized by frontal, parietal, and basal ganglia disease. Aim to assess severity of apraxia in dementia syndromes. Methods: Eight hundred and ten dementia patients were evaluated for apraxia severity through a clinical database program. All results were compared to type of dementia, MMSE and clinical dementia rating. Results: While there is positive correlation between apraxia scores and Mini-Mental Status Examination (MMSE) (r ¼ 0.67, p < 0.0001), there is negative correlation between apraxia and clinical dementia rating (r ¼ 0.67, p < 0.001). Apraxia was seen more severe amongst degenerative dementias including Alzheimer’s, Frontotemporal dementia, Lewy body dementia and Parkinson (r ¼ 0.57, p < 0.001). Vascular dementia was second order frequency (r ¼ 0.48 p < 0.001). Conclusions: Apraxia is observed frequencely amongst dementia syndromes. The severity and frequency of apraxia is due to severity and involvement of syndromes. Thus cortical degenerative causes are more responsible for apraxia than vascular causes.
P4-183
PRION
Simon Mead, MRC Prion Unit, London, United Kingdom. Background: Prion diseases are rare fatal neurodegenerative disorders associated with aggregates of misfolded prion protein. There are several parallels with Alzheimer’s disease including clinical features, molecular mechanisms and neuropathology. The natural history and early signs associated with human prion diseases have not been well defined. There are no validated progression scales or biomarkers for use in a clinical trial setting. Methods: At the UK NHS National Prion Clinic we have systematically assessed and followed up around 350 patients in clinical trial-like or observational cohort studies to help solve these problems. The protocol and enrollment criteria allow for recruitment of patients at risk of disease due to exposure to possibly prion-infected blood or through prion protein gene mutation in order to capture the presymptomatic and earliest clinical stages of disease. Results: We report the assessment of 8 rating methodologies and development of a bespoke composite rating scale for progression based on completion rates, validity and performance in simulated clinical trials. This new MRC scale is composed of a modification of questions derived from the Barthel ADL, the Glasgow Coma Scale and the Clinicians Dementia Rating scale. We show that the scale is suitable for use over the telephone, allowing for documentation of rapid clinical decline at a distance. As part of this work we have performed more than 120 quantitative MRI scans allowing for the development of imaging biomarkers. We are also evaluating the role of a blood test for abnormal prion protein. Conclusions: We describe an ongoing study which may be used as an example of one way to tackle the problem of clinical research in a rare dementia. The development of rating scales and biomarkers in prion disease have parallels and distinctions from Alzheimer’s disease.
P4-184
PROFILE OF SELECTIVE ORL1 ANTAGONIST DEMONSTRATES MECHANISM SAFE TO TARGET FOR SYMPTOMATIC TREATMENT IN ALZHEIMER’S DISEASE
Allen Duplantier, Rathna Iyer, Betty Pettersen, Robin Roof, Julie Cianfrogna, Louis Leung, Michael Brodney, Laura McDowell, Jason Barricklow, Keri Cannon, Cheng Chang, Claire Leurent, Faith Prior, Christine Taylor, Todd Wisialowski, Pfizer Global Research and Development, Groton, Connecticut, United States. Background: Antagonism of the ORL1 receptor has been proposed as a novel mechanism of action to treat Alzheimer’s disease (AD) associated cognitive symptoms. Challenges to the discovery of ORL1 antagonists include selectivity against the m, k and d opioid receptors and retention of ORL1 potency, while modulating the physicochemical properties to achieve low oral dosing and brain availability. From the safety and tolerability perspectives, identifying a selective ORL1 antagonist