- Email: [email protected]
RESULTS OF A PHASE 2 STUDY OF NELOTANSERIN, A NOVEL 5HT2A RECEPTOR INVERSE AGONIST, IN LEWY BODY DEMENTIA SUBJECTS EXPERIENCING VISUAL HALLUCINATIONS
P940
Poster Presentations: Tuesday, July 18, 2017
MRI-based biomarkers of regenerative efficacy. Results: Allopregnanolone at two doses, 2mg and 4mg, was intravenously infused once per week for 12 weeks to 8 participants / dose cohort (6 allopregnanolone + 2 placebo / dose cohort). Within 15 minutes of start of infusion, peak plasma level was reached Cma ¼ 46.34 +/- 23 nanomolar. No sedation was observed in any participant during or after infusion indicating a tolerable dose. The Cmax closely correlated (R¼0.77) with Allo delivered in mg/kg dose. Twelve-week exposure to 2mg or 4mg of Allopregnanolone once per week had no detectable adverse effects. Dose cohort 3 is underway. Primary safety outcomes and secondary exploratory outcomes of MRI based biomarkers, metabolomics, cognition and iPSC derived neural stem cell response to Allo will be presented. Conclusions: Allopregnanolone is a first in class regenerative therapeutic for MCI and AD that targets endogenous neural stem cells and disease modifying mechanisms. Trial outcomes will provide: 1) an estimated safe and well-tolerated dose of Allo; 2) parameter estimates for MRI based markers of regeneration, cognitive efficacy and iPSC / neural stem cell based indicator of responders and foundation to advance to a Phase 2 proof of concept trial of Allo in persons diagnosed with early AD. Supported by NIA U01AG03111 & U01AG047222 to RDB; UF1AG046148 to RDB & LS; ADDF to RDB
P3-026
PILOT TRIAL OF DRONABINOL ADJUNCTIVE TREATMENT OF AGITATION IN ALZHEIMER’S DISEASE (AD) (THC-AD)
Brent Forester1, Caitlin Romano2, William Quayle1, Joanna Georgakas1, Paul B. Rosenberg3, 1McLean Hospital, Belmont, MA, USA; 2Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD, USA; 3Johns Hopkins University School of Medicine, Baltimore, MD, USA. Contact e-mail: bforester@mclean. harvard.edu Background: Agitation in AD is a major cause of burden to patients,
caregivers, and society, and current treatments are limited in efficacy and/or associated with toxicity. Tetrahydrocannabinol (THC) is known to have anxiolytic effects likely mediated through the CB1 cannabinoid receptor, and there is increasing clinical offlabel use of THC in the form of the generic drug dronabinol for agitation in AD. A case series reported improved agitation in AD with mean of 7 mg of dronabinol daily (Woodward MR et al., 2013). A recent randomized controlled trial (RCT) of a similar THC preparation at target dose of 4.5 mg daily was null; however, this study suggested that dosing greater than 4.5mg daily may be required for therapeutic efficacy (van den Elsen et al., 2015). We therefore propose to assess effects of THC on agitation in AD at a higher dose (10 mg daily). Methods: THC-AD is a 3-week, double blind, placebo-controlled RCT, which will evaluate the effects of dronabinol (10 mg daily) vs. placebo on agitation and aggression in inpatients with AD. We will enroll 80 participants, between 60-90 years old, who have been diagnosed with AD (by most recent criteria from McKhann et al., 2011), and are experiencing severe agitation in AD (Agit-AD) as defined by the IPA, 2015. The participants will be inpatients at two sites (Johns Hopkins Bayview Medical Center or McLean Hospital) for the study’s duration. Agitation will be assessed weekly using the PAS and NPI-C as our primary outcome measures. Results: Both sites are planning to enroll participants in February 2017. Compared to placebo, we anticipate dronabinol treatment will be associated with a greater reduction in symptoms of agitation as measured on the PAS and the agitation and aggression domains of the Neuropsychiatric Inventory-Clini-
cian Version (NPI-C). We also believe Dronabinol treatment will be well tolerated with no more than mild adverse events (AEs). Conclusions: THC in the form of the generic drug dronabinol has the potential to treat agitation and aggression in AD. THC-AD is the first U.S. RCT to assess its efficacy for this treatment target.
P3-027
RESULTS OF A PHASE 2 STUDY OF NELOTANSERIN, A NOVEL 5HT2A RECEPTOR INVERSE AGONIST, IN LEWY BODY DEMENTIA SUBJECTS EXPERIENCING VISUAL HALLUCINATIONS
Geetha Ramaswamy1, Warren Wen1, Harald Murck1,2, Lawrence Friedhoff1,3, 1Axovant Sciences, Inc., New York, NY, USA; 2 Philipps-Universit€at Marburg, Clinic of Psychiatry and Psychotherapy, Marburg, Germany; 3Roivant Sciences, Inc., New York, NY, USA. Contact e-mail: [email protected] Background: Lewy body dementia is a common neurodegenerative
disorder that affects approximately 1.4 million individuals in the U.S. alone (Lewy Body Dementia Association). It includes two related disorders: dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). Visual hallucinations affect up to 80% of patients with DLB (Taylor 2011), while up to 75% of patients with PDD are affected by psychosis (Cummings 2014), a condition commonly characterized in this population by hallucinations. Nelotanserin is a selective 5HT2A receptor inverse agonist in development for the treatment of behavioral disturbances, including visual hallucinations, in patients with Lewy body dementia. Nelotanserin has been evaluated in nine completed clinical studies to date with approximately 800 subjects exposed to the drug candidate. This abstract presents data from a Phase 2 study of nelotanserin in DLB and PDD subjects experiencing visual hallucinations. Methods: This is a double-blind, randomized, placebo-controlled crossover study of nelotanserin in Lewy body dementia subjects who are experiencing visual hallucinations (ClinicalTrials.gov: NCT02640729). Subjects in the study must have DLB or PDD, frequent visual hallucinations, and a baseline MMSE score > 18. Subjects are randomized to one of two treatment sequences: nelotanserin in the first treatment period followed by placebo in the second treatment period, or vice versa. The primary outcome measures of the study are extrapyramidal signs as assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) Parts IIþIII, and safety. Secondary outcome measures include observational changes in the severity and frequency of visual hallucinations, including multiple subscales from the Scale for the Assessment of Positive Symptoms (SAPS). Results: Results from the study will be presented at this conference. Conclusions: Nelotanserin is a novel 5HT2A inverse agonist in development for the
Poster Presentations: Tuesday, July 18, 2017
treatment of visual hallucinations in patients with Lewy body dementia. This Phase 2 placebo-controlled study represents an initial effort to develop a new therapy for this significant unmet need. Nelotanserin is also being tested in a separate Phase 2 clinical trial in DLB patients with REM sleep behavior disorder.
P3-028
RISK AND BENEFITS OF ROBOT THERAPY FOR DEMENTIA PATIENTS
Jerzy W. Leszek1, Masahiro Nakano2, Naomi Hachiya3, 1 Wroclaw Medical University Department of Psychiatry, Wroclaw, Poland; 2Kosei General Hospital Department of Psychiatry, Tokyo, Japan; 3R&D Division, Biotechnology Group, Tokyo Metropolitan Industrial Technology Research Institute, Tokyo, Japan. Contact e-mail: [email protected] Background: Robot therapy has increasingly become the focus of atten-
tion as one of a non-pharmacological therapy for elderly dementia patients in recent years. Although this therapeutic approach is found to be useful, it has not been studied yet according to types of diseases, such as Alzheimer’s disease(AD) or Vascular Dementia(VaD) Methods: We have performed reality orientation(RO) for elder dementia patients with/without humanoid robot and analyzed its effectiveness. Thirtyone dementia patients were picked up randomly from Psychiatric unit, healthcare facility and group home for the elderly diagnosed as functional assessment staging 5.Types of diseases are following: there were 12 of AD and 18 VaD, 23 of female and 7 of male and mean age was 81.4+/- 6.2. Patients were divided two groups, on half of them performed RO with humanoid robot.RO session was made 10 times after 7 days interval. Before and after all of RO sessions, we evaluated the effectiveness in detail using NM-scale, Communication scale(Holden), N-ADL and HDS-R which is suitable for analysis for Japanese elderly dementia patients. Results: We have not found statistically significant difference in the analysis of NMscale, Communication scale (Holden),N-ADL under the treatment of RO with/without humanoid robot.On the contrary, HDS-R score was showed a significant clinical difference, exhibiting the effectiveness of the therapy. Meanwhile, when we analyzed each evaluation results more in detail, the scores of NM scale(housekeeping, interest, conversation and memory) were decreased only on the AD patients but not the VaD. After the RO session with a humanoid, all of AD patients were presented aggressiveness, agitation and anxiety; some of them have to be raised the dose of medical agents. These phenomena were not observed on VaD patients at all. Conclusions: Robot therapy will be one of the powerful tool for the care of elder dementia patients as a non-pharmacological treatment. However, it evokes serious problems such as aggressiveness and agitation in AD patients specifically. Thus, when using this method, we have to endeavor to keep the status of patients especially in AD
P3-029
CYPROTERONE ACETATE TO TREAT MODERATE TO SEVERE INAPPROPRIATE SEXUAL BEHAVIOR IN DEMENTIA
Jung Min Pyun1, Young Ho Park1, SangYun Kim2, 1Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seongnam, Republic of South Korea; 2Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seoungnam, Republic of South Korea. Contact e-mail: [email protected] Background: Although inappropriate sexual behavior (ISB) is not
uncommon and causes much distress in patients with dementia
P941
and their caregivers, treatments for ISB have not been well studied. We investigated whether cyproterone acetate is effective in reducing moderate to severe ISB and whether it induces side effects. Methods: A consecutive series of 9 elderly male patients with dementia who visited Neurocognitive Behavior Center of Seoul National University Bundang Hospital between April 2014 and September 2016 and exhibited moderate to severe ISB which did not respond to nonpharmacological treatments was treated with cyproterone acetate. Their diagnoses were as follows: four with Alzheimer’s disease, three with mixed dementia, one with vascular dementia and one with dementia with Lewy bodies. Results: Cyproterone acetate effectively reduced ISB in all the patients except one patient with mixed dementia. Four patients responded to cyproterone acetate 25mg twice a day, whereas three patients responded 50mg twice a day. One patient with Alzheimer’s disease responded to 75mg twice a day, but he discontinued cyproterone acetate due to depression and fatigue. There were no laboratory abnormalities associated with cyproterone acetate in all of the patients. Conclusions: In this small pilot study, cyproterone acetate at a dose of 25 to 50mg twice a day could be considered as an effective treatment for moderate to severe ISB. Although the side effects were not serious, it needs to be studied in a larger sample size.
P3-030
WITHDRAWN
P3-031
THE RELATIONSHIP BETWEEN CAROTID STENOSIS EVALUATION AND STROKE PREVENTION IN HYPERTENSIVE DIABETES AND PATIENTS WITHOUT DIABETES
Cristian Romeo S. Revnic1, Catalina Pena2, Floarea Revnic2, Adriana Sarah Nica3, 1UMF Carol Davila, Bucharest, Romania; 2NIGG Ana Aslan, Bucharest, Romania; 3UMF Carol Davila, Bucharest, Romania. Contact e-mail: [email protected] Background: Atherosclerosis and arterial hypertension are impli-
cated in pathogenesis of Alzheimer‘s disease (AD).The evaluation of intimal thickening of carotid artery is an important parameter in preclinical diagnosis of atherosclerosis and stroke risk in hypertensive elderly patients. The aim of study was to see if there is a relationship between thickening of carotid wall and brain damage in hypertensive elderly patients with/ without diabetes. Methods: Our study has been done on 150 patients( aged 64.31+/-6.8) years old ) divided into two groups of 75 patients each: A with type II diabetes and B nondiabetes, symptomatic with stroke or asymptomatic admitted in Neurological Clinique over three years. At admission the patients were neurologically examined, carotid ultrasound and cranial MRI examinations.. Results: NMR finding were related with white matter lesions and infarctions, these were more frequent in hypertensive diabetic group. In hypertensive nondiabetic there were nonsignificant correlations between NMR findings and thickening of carotid wall .In diabetic patients the associations among cortical lesions clinically symptomatic stroke and increasing in carotid wall thickness were found to be statistically significant in comparison with nondiabetics. NMR abnormalities were present in 92% in group A and 70% in group B consisting of arterial constriction or an atheromatous plaque confirmed by Doppler examination. Conclusions: Measurements of carotid wall thickness via Doppler were considered
Poster Presentations: Tuesday, July 18, 2017
MRI-based biomarkers of regenerative efficacy. Results: Allopregnanolone at two doses, 2mg and 4mg, was intravenously infused once per week for 12 weeks to 8 participants / dose cohort (6 allopregnanolone + 2 placebo / dose cohort). Within 15 minutes of start of infusion, peak plasma level was reached Cma ¼ 46.34 +/- 23 nanomolar. No sedation was observed in any participant during or after infusion indicating a tolerable dose. The Cmax closely correlated (R¼0.77) with Allo delivered in mg/kg dose. Twelve-week exposure to 2mg or 4mg of Allopregnanolone once per week had no detectable adverse effects. Dose cohort 3 is underway. Primary safety outcomes and secondary exploratory outcomes of MRI based biomarkers, metabolomics, cognition and iPSC derived neural stem cell response to Allo will be presented. Conclusions: Allopregnanolone is a first in class regenerative therapeutic for MCI and AD that targets endogenous neural stem cells and disease modifying mechanisms. Trial outcomes will provide: 1) an estimated safe and well-tolerated dose of Allo; 2) parameter estimates for MRI based markers of regeneration, cognitive efficacy and iPSC / neural stem cell based indicator of responders and foundation to advance to a Phase 2 proof of concept trial of Allo in persons diagnosed with early AD. Supported by NIA U01AG03111 & U01AG047222 to RDB; UF1AG046148 to RDB & LS; ADDF to RDB
P3-026
PILOT TRIAL OF DRONABINOL ADJUNCTIVE TREATMENT OF AGITATION IN ALZHEIMER’S DISEASE (AD) (THC-AD)
Brent Forester1, Caitlin Romano2, William Quayle1, Joanna Georgakas1, Paul B. Rosenberg3, 1McLean Hospital, Belmont, MA, USA; 2Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD, USA; 3Johns Hopkins University School of Medicine, Baltimore, MD, USA. Contact e-mail: bforester@mclean. harvard.edu Background: Agitation in AD is a major cause of burden to patients,
caregivers, and society, and current treatments are limited in efficacy and/or associated with toxicity. Tetrahydrocannabinol (THC) is known to have anxiolytic effects likely mediated through the CB1 cannabinoid receptor, and there is increasing clinical offlabel use of THC in the form of the generic drug dronabinol for agitation in AD. A case series reported improved agitation in AD with mean of 7 mg of dronabinol daily (Woodward MR et al., 2013). A recent randomized controlled trial (RCT) of a similar THC preparation at target dose of 4.5 mg daily was null; however, this study suggested that dosing greater than 4.5mg daily may be required for therapeutic efficacy (van den Elsen et al., 2015). We therefore propose to assess effects of THC on agitation in AD at a higher dose (10 mg daily). Methods: THC-AD is a 3-week, double blind, placebo-controlled RCT, which will evaluate the effects of dronabinol (10 mg daily) vs. placebo on agitation and aggression in inpatients with AD. We will enroll 80 participants, between 60-90 years old, who have been diagnosed with AD (by most recent criteria from McKhann et al., 2011), and are experiencing severe agitation in AD (Agit-AD) as defined by the IPA, 2015. The participants will be inpatients at two sites (Johns Hopkins Bayview Medical Center or McLean Hospital) for the study’s duration. Agitation will be assessed weekly using the PAS and NPI-C as our primary outcome measures. Results: Both sites are planning to enroll participants in February 2017. Compared to placebo, we anticipate dronabinol treatment will be associated with a greater reduction in symptoms of agitation as measured on the PAS and the agitation and aggression domains of the Neuropsychiatric Inventory-Clini-
cian Version (NPI-C). We also believe Dronabinol treatment will be well tolerated with no more than mild adverse events (AEs). Conclusions: THC in the form of the generic drug dronabinol has the potential to treat agitation and aggression in AD. THC-AD is the first U.S. RCT to assess its efficacy for this treatment target.
P3-027
RESULTS OF A PHASE 2 STUDY OF NELOTANSERIN, A NOVEL 5HT2A RECEPTOR INVERSE AGONIST, IN LEWY BODY DEMENTIA SUBJECTS EXPERIENCING VISUAL HALLUCINATIONS
Geetha Ramaswamy1, Warren Wen1, Harald Murck1,2, Lawrence Friedhoff1,3, 1Axovant Sciences, Inc., New York, NY, USA; 2 Philipps-Universit€at Marburg, Clinic of Psychiatry and Psychotherapy, Marburg, Germany; 3Roivant Sciences, Inc., New York, NY, USA. Contact e-mail: [email protected] Background: Lewy body dementia is a common neurodegenerative
disorder that affects approximately 1.4 million individuals in the U.S. alone (Lewy Body Dementia Association). It includes two related disorders: dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). Visual hallucinations affect up to 80% of patients with DLB (Taylor 2011), while up to 75% of patients with PDD are affected by psychosis (Cummings 2014), a condition commonly characterized in this population by hallucinations. Nelotanserin is a selective 5HT2A receptor inverse agonist in development for the treatment of behavioral disturbances, including visual hallucinations, in patients with Lewy body dementia. Nelotanserin has been evaluated in nine completed clinical studies to date with approximately 800 subjects exposed to the drug candidate. This abstract presents data from a Phase 2 study of nelotanserin in DLB and PDD subjects experiencing visual hallucinations. Methods: This is a double-blind, randomized, placebo-controlled crossover study of nelotanserin in Lewy body dementia subjects who are experiencing visual hallucinations (ClinicalTrials.gov: NCT02640729). Subjects in the study must have DLB or PDD, frequent visual hallucinations, and a baseline MMSE score > 18. Subjects are randomized to one of two treatment sequences: nelotanserin in the first treatment period followed by placebo in the second treatment period, or vice versa. The primary outcome measures of the study are extrapyramidal signs as assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS) Parts IIþIII, and safety. Secondary outcome measures include observational changes in the severity and frequency of visual hallucinations, including multiple subscales from the Scale for the Assessment of Positive Symptoms (SAPS). Results: Results from the study will be presented at this conference. Conclusions: Nelotanserin is a novel 5HT2A inverse agonist in development for the
Poster Presentations: Tuesday, July 18, 2017
treatment of visual hallucinations in patients with Lewy body dementia. This Phase 2 placebo-controlled study represents an initial effort to develop a new therapy for this significant unmet need. Nelotanserin is also being tested in a separate Phase 2 clinical trial in DLB patients with REM sleep behavior disorder.
P3-028
RISK AND BENEFITS OF ROBOT THERAPY FOR DEMENTIA PATIENTS
Jerzy W. Leszek1, Masahiro Nakano2, Naomi Hachiya3, 1 Wroclaw Medical University Department of Psychiatry, Wroclaw, Poland; 2Kosei General Hospital Department of Psychiatry, Tokyo, Japan; 3R&D Division, Biotechnology Group, Tokyo Metropolitan Industrial Technology Research Institute, Tokyo, Japan. Contact e-mail: [email protected] Background: Robot therapy has increasingly become the focus of atten-
tion as one of a non-pharmacological therapy for elderly dementia patients in recent years. Although this therapeutic approach is found to be useful, it has not been studied yet according to types of diseases, such as Alzheimer’s disease(AD) or Vascular Dementia(VaD) Methods: We have performed reality orientation(RO) for elder dementia patients with/without humanoid robot and analyzed its effectiveness. Thirtyone dementia patients were picked up randomly from Psychiatric unit, healthcare facility and group home for the elderly diagnosed as functional assessment staging 5.Types of diseases are following: there were 12 of AD and 18 VaD, 23 of female and 7 of male and mean age was 81.4+/- 6.2. Patients were divided two groups, on half of them performed RO with humanoid robot.RO session was made 10 times after 7 days interval. Before and after all of RO sessions, we evaluated the effectiveness in detail using NM-scale, Communication scale(Holden), N-ADL and HDS-R which is suitable for analysis for Japanese elderly dementia patients. Results: We have not found statistically significant difference in the analysis of NMscale, Communication scale (Holden),N-ADL under the treatment of RO with/without humanoid robot.On the contrary, HDS-R score was showed a significant clinical difference, exhibiting the effectiveness of the therapy. Meanwhile, when we analyzed each evaluation results more in detail, the scores of NM scale(housekeeping, interest, conversation and memory) were decreased only on the AD patients but not the VaD. After the RO session with a humanoid, all of AD patients were presented aggressiveness, agitation and anxiety; some of them have to be raised the dose of medical agents. These phenomena were not observed on VaD patients at all. Conclusions: Robot therapy will be one of the powerful tool for the care of elder dementia patients as a non-pharmacological treatment. However, it evokes serious problems such as aggressiveness and agitation in AD patients specifically. Thus, when using this method, we have to endeavor to keep the status of patients especially in AD
P3-029
CYPROTERONE ACETATE TO TREAT MODERATE TO SEVERE INAPPROPRIATE SEXUAL BEHAVIOR IN DEMENTIA
Jung Min Pyun1, Young Ho Park1, SangYun Kim2, 1Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seongnam, Republic of South Korea; 2Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seoungnam, Republic of South Korea. Contact e-mail: [email protected] Background: Although inappropriate sexual behavior (ISB) is not
uncommon and causes much distress in patients with dementia
P941
and their caregivers, treatments for ISB have not been well studied. We investigated whether cyproterone acetate is effective in reducing moderate to severe ISB and whether it induces side effects. Methods: A consecutive series of 9 elderly male patients with dementia who visited Neurocognitive Behavior Center of Seoul National University Bundang Hospital between April 2014 and September 2016 and exhibited moderate to severe ISB which did not respond to nonpharmacological treatments was treated with cyproterone acetate. Their diagnoses were as follows: four with Alzheimer’s disease, three with mixed dementia, one with vascular dementia and one with dementia with Lewy bodies. Results: Cyproterone acetate effectively reduced ISB in all the patients except one patient with mixed dementia. Four patients responded to cyproterone acetate 25mg twice a day, whereas three patients responded 50mg twice a day. One patient with Alzheimer’s disease responded to 75mg twice a day, but he discontinued cyproterone acetate due to depression and fatigue. There were no laboratory abnormalities associated with cyproterone acetate in all of the patients. Conclusions: In this small pilot study, cyproterone acetate at a dose of 25 to 50mg twice a day could be considered as an effective treatment for moderate to severe ISB. Although the side effects were not serious, it needs to be studied in a larger sample size.
P3-030
WITHDRAWN
P3-031
THE RELATIONSHIP BETWEEN CAROTID STENOSIS EVALUATION AND STROKE PREVENTION IN HYPERTENSIVE DIABETES AND PATIENTS WITHOUT DIABETES
Cristian Romeo S. Revnic1, Catalina Pena2, Floarea Revnic2, Adriana Sarah Nica3, 1UMF Carol Davila, Bucharest, Romania; 2NIGG Ana Aslan, Bucharest, Romania; 3UMF Carol Davila, Bucharest, Romania. Contact e-mail: [email protected] Background: Atherosclerosis and arterial hypertension are impli-
cated in pathogenesis of Alzheimer‘s disease (AD).The evaluation of intimal thickening of carotid artery is an important parameter in preclinical diagnosis of atherosclerosis and stroke risk in hypertensive elderly patients. The aim of study was to see if there is a relationship between thickening of carotid wall and brain damage in hypertensive elderly patients with/ without diabetes. Methods: Our study has been done on 150 patients( aged 64.31+/-6.8) years old ) divided into two groups of 75 patients each: A with type II diabetes and B nondiabetes, symptomatic with stroke or asymptomatic admitted in Neurological Clinique over three years. At admission the patients were neurologically examined, carotid ultrasound and cranial MRI examinations.. Results: NMR finding were related with white matter lesions and infarctions, these were more frequent in hypertensive diabetic group. In hypertensive nondiabetic there were nonsignificant correlations between NMR findings and thickening of carotid wall .In diabetic patients the associations among cortical lesions clinically symptomatic stroke and increasing in carotid wall thickness were found to be statistically significant in comparison with nondiabetics. NMR abnormalities were present in 92% in group A and 70% in group B consisting of arterial constriction or an atheromatous plaque confirmed by Doppler examination. Conclusions: Measurements of carotid wall thickness via Doppler were considered