Disruption in cholinergic neurotransmission is one of the earliest neuropathological changes in p... more Disruption in cholinergic neurotransmission is one of the earliest neuropathological changes in preclinical Alzheimer's disease (AD) and may be associated with abnormal beta-amyloid (Aβ) accumulation. Therefore, disruption of cholinergic neurotransmission with scopolamine may unmask otherwise undetectable cognitive deficits in preclinical AD. To compare the effects of low-dose (0.20 mg s.c.) scopolamine on cognition between Aβ+ and Aβ- cognitively normal (CN) older adults using the Groton Maze Learning Test (GMLT). CN older adults completed the GMLT predose and then received scopolamine (0.20 mg) subcutaneously. Participants were reassessed 1-, 3-, 5-, 7-, and 8-hours post dose. All participants underwent positron emission tomography neuroimaging for Aβ using (18)F-florbetapir within 6 weeks of their baseline visit. Rhode Island Hospital Clinical Research Center, Providence, USA. CN older adults (n = 63), with a family history of AD and subjective memory complaints were enrolled...
To investigate whether variations within normal ranges of thyroid functioning are related to cogn... more To investigate whether variations within normal ranges of thyroid functioning are related to cognitive and neuropsychiatric functioning in Alzheimer disease (AD). Mild alterations of thyroid hormone levels, even in the normal range, are associated with changes in mood and cognitive functioning in older, nondemented adults, and lower concentrations of thyroid hormones have been shown to be associated with an increased risk for cognitive decline. Less is known about the relationship between thyroid hormone levels and cognitive and neuropsychiatric dysfunction in AD. Twenty-eight euthyroid patients with AD on donepezil underwent evaluation of thyroid status, including measures of thyroid-stimulating hormone (TSH) and free thyroxine (FT4), and cognitive and neuropsychiatric assessment with the Alzheimer's Disease Assessment Scale, Neuropsychiatric Inventory, and Visual Analog Mood Scales. Correlational analyses indicated statistically significant associations between FT4 concentrati...
To differentiate driving errors in persons with dementia who fail a performance- based road test ... more To differentiate driving errors in persons with dementia who fail a performance- based road test from errors in persons who pass. Cross-sectional. Community. Active drivers diagnosed with dementia (n = 60) and older adult controls (n = 32). All participants completed a standardized clinical and on-road driving assessment. The outcome variable was the number and types of driving errors according to the Record of Driving Errors (RODE), a standardized tool to record driving errors. Sixty-two percent (n = 37) of individuals with dementia and 3% (n = 1) of controls failed the road test. Based on the RODE, individuals with dementia made twice as many driving errors as healthy controls. Within the dementia sample, individuals who failed the road test had more difficulties driving straight and making left and right turns than during lane changes. Dangerous actions occurred most often while driving straight and making left turns. Specific driving behaviors associated with road test failure in the sample with dementia included difficulties in lane positioning and usage, stopping the vehicle appropriately, attention, decision-making, and following rules of the road. Informants of participants with dementia who failed the road test reported more impairment with cognitive functioning on the Assessing Dementia 8 Screening Interview (AD8). This report highlights the driving errors most common in people with dementia who fail a road test. The finding that most of the dangerous actions in the sample with dementia occurred while driving straight condition is novel. Driving on straight roads has not been considered a condition of "high challenge" in prior driving studies in individuals with dementia. This finding has potential implications for future interventions related to vehicle instrumentation and driving recommendations for people with dementia.
To determine the validity and reliability of clinician ratings of the driving competence of patie... more To determine the validity and reliability of clinician ratings of the driving competence of patients with mild dementia. Observational study of a cross-section of drivers with mild dementia based on chart review by clinicians with varying types of expertise and experience. Outpatient dementia clinic. Fifty dementia subjects from a longitudinal study of driving and dementia. Each clinician reviewed information from the clinic charts and the first study visit. The clinician then rated the drivers as safe, marginal, or unsafe. A professional driving instructor compared these ratings with total driving scores on a standardized road test and categorical ratings of driving competence. Clinicians also completed a visual analog scale assessment of variables that led to their determinations of driving competence. Accuracy of clinician ratings ranged from 62% to 78% for the instructor's global rating of safe versus marginal or unsafe. In general, there was moderate accuracy and interrater...
1. INTRODUCTION Little is known about quality of life (QOL) in vascular dementia (VaD). The past ... more 1. INTRODUCTION Little is known about quality of life (QOL) in vascular dementia (VaD). The past decade has witnessed considerable attention to QOL issues in dementia, but the majority of this work has been conducted with Alzheimer's disease (AD) or mixed dementia ...
The American journal of occupational therapy : official publication of the American Occupational Therapy Association
This observational study investigated family caregiver and clinician ratings of 75 drivers with A... more This observational study investigated family caregiver and clinician ratings of 75 drivers with Alzheimer's disease against scores on a standardized road test and a naturalistic driving evaluation. Clinician ratings by a physician specialized in dementia were significantly associated with road test error scores (r = .25, p = .03) but not naturalistic driving errors or global ratings of road test and naturalistic driving performance. Caregiver ratings were unrelated to either driving assessment, with two exceptions; adult child ratings of driving ability were correlated with road test error scores (r = .43, p = .02), and spousal ratings were inversely correlated with global ratings. Clinician ratings of driving competence were modestly correlated with road test performance, but caregiver ratings were more complex. Adult children may be more accurate reporters of driving ability than spouses, possibly because of less personal bias, but the reasons behind this discrepancy need furt...
Physicians in Rhode Island sometimes find it difficult to advise patients about returning to driv... more Physicians in Rhode Island sometimes find it difficult to advise patients about returning to driving after they present with a seizure or syncopal episode due to lack of statutory or professional guidance on the issue. We provide an overview of the medical literature on public policies and recommendations regarding driving after seizures or syncope. We also present the laws in Rhode Island regarding physician notification of the medical advisory board of the Department of Motor Vehicles, legal obligations, and immunity from prosecution for those who report. Finally, we present the results of a survey of current practice by Rhode Island neurologists when they advise patients who have had a recent seizure or unexplained syncopal event. Based upon this information, we hope local practitioners are empowered in their decision making on driving restrictions and we hope this data informs future public policy efforts.
Over the past 10 years, several instruments developed specifically for the assessment of Quality ... more Over the past 10 years, several instruments developed specifically for the assessment of Quality of Life (QOL) in dementia have been introduced. The goal of the current review is to present, compare, and critique existing QOL measures for dementia populations to assist investigators and clinicians in selecting the optimal inventory for their specific needs. Nine measures are reviewed with a focus on conceptualizations of QOL, psychometric data, targeted patient population, and administration and scoring procedures. Critical discussion and comparison of the instruments is presented after the scales are described individually. Differences in definitions of QOL, assessment procedures, and methods that were used to establish the validity of instruments are highlighted. An important direction for future research on QOL scales for dementia is to establish their responsiveness to change over time. It will also be important to identify factors that affect reports of QOL, determine the how p...
To examine the relationship between gender and specific types of behavior problems that occur in ... more To examine the relationship between gender and specific types of behavior problems that occur in patients with Alzheimer's disease. This was an observational study using the Dementia Behavior Disturbance Scale to quantify and define behavioral problems encountered by caregivers. Multiple regressions were used to control for the possible influence of dementia severity as measured by the Mini-Mental State Examination and the duration of dementia. Patients were sampled from the outpatient dementia clinics of Roger Williams Hospital and Miriam Hospital in Providence, Rhode Island. A total of 125 patients with probable Alzheimer's disease, defined by NINCDS-ADRDA diagnostic criteria, were included in the study. There were 75 women and 50 men. Caregivers rated the presence and frequency of 28 different behavior problems from the Dementia Behavior Disturbance Scale. Domains of behavior disturbance were then defined by a factor analysis of the data. Male and female groups were compa...
The American journal of occupational therapy : official publication of the American Occupational Therapy Association
OBJECTIVE. The aim of this study was to develop a brief screening battery to predict the on-road ... more OBJECTIVE. The aim of this study was to develop a brief screening battery to predict the on-road performance of drivers who had experienced a stroke. METHOD. We examined 72 people with stroke referred by community physicians to an academic rehabilitation center. The outcome variable was pass or fail on the modified Washington University Road Test. Predictor measures were tests of visual, motor, and cognitive functioning. RESULTS. The best predictive model for failure on the road test included Trail Making Test Part A and the Snellgrove Maze Task(®). CONCLUSION. A screening battery that can be performed in less than 5 min was able to assist in the prediction of road test performance in a sample of drivers with stroke. A probability of failure calculator may be useful for clinicians in their decision to refer clients with stroke for a comprehensive driving evaluation.
To examine the sensitivity and specificity of the Assessment of Driving-Related Skills (ADReS), a... more To examine the sensitivity and specificity of the Assessment of Driving-Related Skills (ADReS), a clinical tool recommended by the American Medical Association for identifying potentially unsafe older drivers that includes tests of vision, motor function, and cognition. Cross-sectional observation study. Memory assessment outpatient clinic of a university hospital. Drivers with normal cognition (n = 47) and cognitive impairment (n = 75). A neurologist completed the ADReS during an office visit. Additional cognitive tests of executive, visuospatial, and visuomotor function were also performed. On a separate day, participants completed a standardized on-road test, assessed by a professional driving instructor using a global safety rating and a quantitative driving score. In this sample of currently active older drivers with and without cognitive impairment, measures of cognition-particularly the Trail-Making Test Part B-were more highly correlated with driving scores than other measures of function. Using recommended scoring procedures, the ADReS had a sensitivity of 0.81 for detecting impaired driving on the road test, with a specificity of 0.32 and an area under the receiver operating characteristic curve (AUC) of 0.57. A logistic regression model that incorporated computerized maze task and Mini-Mental State Examination scores improved overall classification accuracy, yielding a sensitivity of 0.61, a specificity of 0.84, and an AUC of 0.80. In its present form, the ADReS has limited utility as an office screen for individuals who should undergo formal driving assessment. Improved scoring methods and screening tests with greater diagnostic accuracy than the ADReS are needed for general office practice.
Proceedings of the National Academy of Sciences of the United States of America, Jan 6, 2012
Visual cortical surface area varies two- to threefold between human individuals, is highly herita... more Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P(combined) = 3.2 × 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the…
Journal of Geriatric Psychiatry and Neurology, 2003
The authors previously reported that subcortical hyperintensity (SH) and whole-brain volume (WBV)... more The authors previously reported that subcortical hyperintensity (SH) and whole-brain volume (WBV) each covary with different subscale scores of the Mattis Dementia Rating Scale (MDRS) among vascular dementia (VaD) patients. The present longitudinal analysis examined these relationships for change. The authors found that SH volume increased and WBV decreased significantly over 12 months. At baseline, SH volume accounted for significant variance in MDRS total score and every subscale score, except Memory. WBV was unrelated to any MDRS measure. After 12 months, SH volume was related only to the Construction subscale score, whereas WBV accounted for the majority of variance in Attention and Memory subscale performance. These findings indicate that although SH volume increases with disease progression, the relative impact of SH volume on cognitive status decreases among patients with advanced VaD.
Disruption in cholinergic neurotransmission is one of the earliest neuropathological changes in p... more Disruption in cholinergic neurotransmission is one of the earliest neuropathological changes in preclinical Alzheimer's disease (AD) and may be associated with abnormal beta-amyloid (Aβ) accumulation. Therefore, disruption of cholinergic neurotransmission with scopolamine may unmask otherwise undetectable cognitive deficits in preclinical AD. To compare the effects of low-dose (0.20 mg s.c.) scopolamine on cognition between Aβ+ and Aβ- cognitively normal (CN) older adults using the Groton Maze Learning Test (GMLT). CN older adults completed the GMLT predose and then received scopolamine (0.20 mg) subcutaneously. Participants were reassessed 1-, 3-, 5-, 7-, and 8-hours post dose. All participants underwent positron emission tomography neuroimaging for Aβ using (18)F-florbetapir within 6 weeks of their baseline visit. Rhode Island Hospital Clinical Research Center, Providence, USA. CN older adults (n = 63), with a family history of AD and subjective memory complaints were enrolled...
To investigate whether variations within normal ranges of thyroid functioning are related to cogn... more To investigate whether variations within normal ranges of thyroid functioning are related to cognitive and neuropsychiatric functioning in Alzheimer disease (AD). Mild alterations of thyroid hormone levels, even in the normal range, are associated with changes in mood and cognitive functioning in older, nondemented adults, and lower concentrations of thyroid hormones have been shown to be associated with an increased risk for cognitive decline. Less is known about the relationship between thyroid hormone levels and cognitive and neuropsychiatric dysfunction in AD. Twenty-eight euthyroid patients with AD on donepezil underwent evaluation of thyroid status, including measures of thyroid-stimulating hormone (TSH) and free thyroxine (FT4), and cognitive and neuropsychiatric assessment with the Alzheimer's Disease Assessment Scale, Neuropsychiatric Inventory, and Visual Analog Mood Scales. Correlational analyses indicated statistically significant associations between FT4 concentrati...
To differentiate driving errors in persons with dementia who fail a performance- based road test ... more To differentiate driving errors in persons with dementia who fail a performance- based road test from errors in persons who pass. Cross-sectional. Community. Active drivers diagnosed with dementia (n = 60) and older adult controls (n = 32). All participants completed a standardized clinical and on-road driving assessment. The outcome variable was the number and types of driving errors according to the Record of Driving Errors (RODE), a standardized tool to record driving errors. Sixty-two percent (n = 37) of individuals with dementia and 3% (n = 1) of controls failed the road test. Based on the RODE, individuals with dementia made twice as many driving errors as healthy controls. Within the dementia sample, individuals who failed the road test had more difficulties driving straight and making left and right turns than during lane changes. Dangerous actions occurred most often while driving straight and making left turns. Specific driving behaviors associated with road test failure in the sample with dementia included difficulties in lane positioning and usage, stopping the vehicle appropriately, attention, decision-making, and following rules of the road. Informants of participants with dementia who failed the road test reported more impairment with cognitive functioning on the Assessing Dementia 8 Screening Interview (AD8). This report highlights the driving errors most common in people with dementia who fail a road test. The finding that most of the dangerous actions in the sample with dementia occurred while driving straight condition is novel. Driving on straight roads has not been considered a condition of "high challenge" in prior driving studies in individuals with dementia. This finding has potential implications for future interventions related to vehicle instrumentation and driving recommendations for people with dementia.
To determine the validity and reliability of clinician ratings of the driving competence of patie... more To determine the validity and reliability of clinician ratings of the driving competence of patients with mild dementia. Observational study of a cross-section of drivers with mild dementia based on chart review by clinicians with varying types of expertise and experience. Outpatient dementia clinic. Fifty dementia subjects from a longitudinal study of driving and dementia. Each clinician reviewed information from the clinic charts and the first study visit. The clinician then rated the drivers as safe, marginal, or unsafe. A professional driving instructor compared these ratings with total driving scores on a standardized road test and categorical ratings of driving competence. Clinicians also completed a visual analog scale assessment of variables that led to their determinations of driving competence. Accuracy of clinician ratings ranged from 62% to 78% for the instructor's global rating of safe versus marginal or unsafe. In general, there was moderate accuracy and interrater...
1. INTRODUCTION Little is known about quality of life (QOL) in vascular dementia (VaD). The past ... more 1. INTRODUCTION Little is known about quality of life (QOL) in vascular dementia (VaD). The past decade has witnessed considerable attention to QOL issues in dementia, but the majority of this work has been conducted with Alzheimer's disease (AD) or mixed dementia ...
The American journal of occupational therapy : official publication of the American Occupational Therapy Association
This observational study investigated family caregiver and clinician ratings of 75 drivers with A... more This observational study investigated family caregiver and clinician ratings of 75 drivers with Alzheimer's disease against scores on a standardized road test and a naturalistic driving evaluation. Clinician ratings by a physician specialized in dementia were significantly associated with road test error scores (r = .25, p = .03) but not naturalistic driving errors or global ratings of road test and naturalistic driving performance. Caregiver ratings were unrelated to either driving assessment, with two exceptions; adult child ratings of driving ability were correlated with road test error scores (r = .43, p = .02), and spousal ratings were inversely correlated with global ratings. Clinician ratings of driving competence were modestly correlated with road test performance, but caregiver ratings were more complex. Adult children may be more accurate reporters of driving ability than spouses, possibly because of less personal bias, but the reasons behind this discrepancy need furt...
Physicians in Rhode Island sometimes find it difficult to advise patients about returning to driv... more Physicians in Rhode Island sometimes find it difficult to advise patients about returning to driving after they present with a seizure or syncopal episode due to lack of statutory or professional guidance on the issue. We provide an overview of the medical literature on public policies and recommendations regarding driving after seizures or syncope. We also present the laws in Rhode Island regarding physician notification of the medical advisory board of the Department of Motor Vehicles, legal obligations, and immunity from prosecution for those who report. Finally, we present the results of a survey of current practice by Rhode Island neurologists when they advise patients who have had a recent seizure or unexplained syncopal event. Based upon this information, we hope local practitioners are empowered in their decision making on driving restrictions and we hope this data informs future public policy efforts.
Over the past 10 years, several instruments developed specifically for the assessment of Quality ... more Over the past 10 years, several instruments developed specifically for the assessment of Quality of Life (QOL) in dementia have been introduced. The goal of the current review is to present, compare, and critique existing QOL measures for dementia populations to assist investigators and clinicians in selecting the optimal inventory for their specific needs. Nine measures are reviewed with a focus on conceptualizations of QOL, psychometric data, targeted patient population, and administration and scoring procedures. Critical discussion and comparison of the instruments is presented after the scales are described individually. Differences in definitions of QOL, assessment procedures, and methods that were used to establish the validity of instruments are highlighted. An important direction for future research on QOL scales for dementia is to establish their responsiveness to change over time. It will also be important to identify factors that affect reports of QOL, determine the how p...
To examine the relationship between gender and specific types of behavior problems that occur in ... more To examine the relationship between gender and specific types of behavior problems that occur in patients with Alzheimer's disease. This was an observational study using the Dementia Behavior Disturbance Scale to quantify and define behavioral problems encountered by caregivers. Multiple regressions were used to control for the possible influence of dementia severity as measured by the Mini-Mental State Examination and the duration of dementia. Patients were sampled from the outpatient dementia clinics of Roger Williams Hospital and Miriam Hospital in Providence, Rhode Island. A total of 125 patients with probable Alzheimer's disease, defined by NINCDS-ADRDA diagnostic criteria, were included in the study. There were 75 women and 50 men. Caregivers rated the presence and frequency of 28 different behavior problems from the Dementia Behavior Disturbance Scale. Domains of behavior disturbance were then defined by a factor analysis of the data. Male and female groups were compa...
The American journal of occupational therapy : official publication of the American Occupational Therapy Association
OBJECTIVE. The aim of this study was to develop a brief screening battery to predict the on-road ... more OBJECTIVE. The aim of this study was to develop a brief screening battery to predict the on-road performance of drivers who had experienced a stroke. METHOD. We examined 72 people with stroke referred by community physicians to an academic rehabilitation center. The outcome variable was pass or fail on the modified Washington University Road Test. Predictor measures were tests of visual, motor, and cognitive functioning. RESULTS. The best predictive model for failure on the road test included Trail Making Test Part A and the Snellgrove Maze Task(®). CONCLUSION. A screening battery that can be performed in less than 5 min was able to assist in the prediction of road test performance in a sample of drivers with stroke. A probability of failure calculator may be useful for clinicians in their decision to refer clients with stroke for a comprehensive driving evaluation.
To examine the sensitivity and specificity of the Assessment of Driving-Related Skills (ADReS), a... more To examine the sensitivity and specificity of the Assessment of Driving-Related Skills (ADReS), a clinical tool recommended by the American Medical Association for identifying potentially unsafe older drivers that includes tests of vision, motor function, and cognition. Cross-sectional observation study. Memory assessment outpatient clinic of a university hospital. Drivers with normal cognition (n = 47) and cognitive impairment (n = 75). A neurologist completed the ADReS during an office visit. Additional cognitive tests of executive, visuospatial, and visuomotor function were also performed. On a separate day, participants completed a standardized on-road test, assessed by a professional driving instructor using a global safety rating and a quantitative driving score. In this sample of currently active older drivers with and without cognitive impairment, measures of cognition-particularly the Trail-Making Test Part B-were more highly correlated with driving scores than other measures of function. Using recommended scoring procedures, the ADReS had a sensitivity of 0.81 for detecting impaired driving on the road test, with a specificity of 0.32 and an area under the receiver operating characteristic curve (AUC) of 0.57. A logistic regression model that incorporated computerized maze task and Mini-Mental State Examination scores improved overall classification accuracy, yielding a sensitivity of 0.61, a specificity of 0.84, and an AUC of 0.80. In its present form, the ADReS has limited utility as an office screen for individuals who should undergo formal driving assessment. Improved scoring methods and screening tests with greater diagnostic accuracy than the ADReS are needed for general office practice.
Proceedings of the National Academy of Sciences of the United States of America, Jan 6, 2012
Visual cortical surface area varies two- to threefold between human individuals, is highly herita... more Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P(combined) = 3.2 × 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the…
Journal of Geriatric Psychiatry and Neurology, 2003
The authors previously reported that subcortical hyperintensity (SH) and whole-brain volume (WBV)... more The authors previously reported that subcortical hyperintensity (SH) and whole-brain volume (WBV) each covary with different subscale scores of the Mattis Dementia Rating Scale (MDRS) among vascular dementia (VaD) patients. The present longitudinal analysis examined these relationships for change. The authors found that SH volume increased and WBV decreased significantly over 12 months. At baseline, SH volume accounted for significant variance in MDRS total score and every subscale score, except Memory. WBV was unrelated to any MDRS measure. After 12 months, SH volume was related only to the Construction subscale score, whereas WBV accounted for the majority of variance in Attention and Memory subscale performance. These findings indicate that although SH volume increases with disease progression, the relative impact of SH volume on cognitive status decreases among patients with advanced VaD.
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Papers by Brian Ott