Rich Einstein - Academia.edu (original) (raw)

Papers by Rich Einstein

Research paper thumbnail of Headache prevention outcome and body mass index

Cephalalgia, 2006

A population-based longitudinal study suggests that obesity is a strong risk factor for the devel... more A population-based longitudinal study suggests that obesity is a strong risk factor for the development of headaches on 15 or more days per month. Little is know about the influence of weight on the response to headache preventive treatment. Herein we prospectively assessed the influence of the baseline body mass index (BMI) on the response to headache preventive treatment. We included adults with episodic or chronic migraine (ICHD-2), or transformed migraine (Silberstein and Lipton criteria) that sought care in a headache clinic. BMI was assessed in the first visit. Baseline information included headache frequency, number of days with severe headache (prospectively obtained over 1 month), and headache-related disability (HIT-6). The same information was obtained after 3 months of preventive treatment. Subjects were categorized based on BMI in: normal weight ( ≤ 24.9), overweight (25-29.9), or obese ( ≥ 30). We contrasted the headache end-points using ANOVA with post-test and Kruskal-Wallis with post-test. We used logistic regression to model BMI and headache parameters adjusting for covariates. Our sample consisted of 176 subjects (79.5% women, mean of 44.4 years). At baseline 40.9% had normal weight, 29.5% were overweight and 27.3% were obese. No significant differences were observed in the number of headache days at baseline. After treatment, frequency declined in the entire population, but no significant differences were found by BMI group. Regarding the number of days with severe pain per month, there were also no significant differences at baseline (normal = 6.1, overweight = 6.5, obese = 6.7), and improvement overall ( P = 0.01). However, changes were greater in the obese (reduction in 2.7 days with treatment) and overweight (3.9) vs. normal (1.5, P < 0.01). Finally, HIT scores at baseline did not differ by BMI group (normal weight = 63.8, overweight = 64.1, obese = 63.6). However, compared with the normal weighted group, change in HIT scores (followup baseline) were greater in the obese (6.4 vs. 3.5, P < 0.05) and overweight groups (6.8 vs. 3.5, P < 0.05). In the logistic regression model, BMI did not account for changes in disability, headache frequency, or in the number of days with severe headache per month, after adjusting for covariates. Contrary to what we hypothesized, obesity at baseline does not seem to be related to follow-up refractoriness to preventive treatment. ᮀ Migraine, preventive treatment, obesity, body mass index

Research paper thumbnail of Mitochondrial Dysfunction and MigraineEvidence and Hypotheses

Cephalalgia, 2006

The molecular basis of migraine is still not completely understood. An impairment of mitochondria... more The molecular basis of migraine is still not completely understood. An impairment of mitochondrial oxidative metabolism might play a role in the pathophysiology of this disease, by influencing neuronal information processing. Biochemical assays of platelets and muscle biopsies performed in migraine sufferers have shown a decreased activity of the respiratory chain enzymes. Studies with phosphorus magnetic resonance spectroscopy ( 31 P-MRS) have demonstrated an impairment of the brain oxidative energy metabolism both during and between migraine attacks. However, molecular genetic studies have not detected specific mitochondrial DNA (mtDNA) mutations in patients with migraine, although other studies suggest that particular genetic markers (i.e. neutral polymorphisms or secondary mtDNA mutations) might be present in some migraine sufferers. Further studies are still needed to clarify if migraine is associated with unidentified mutations on the mtDNA or on nuclear genes that code mitochondrial proteins. In this paper, we review morphological, biochemical, imaging and genetic studies which bear on the hypothesis that migraine may be related to mitochondrial dysfunction at least in some individuals. ᮀ Brain oxidative metabolism, magnetic resonance spectroscopy, migraine, mitochondrial dysfunction, mutation

Research paper thumbnail of Identification of epidural neoplasm. Radiography and bone scintigraphy in the symptomatic and asymptomatic spine

Cancer, 1989

Early identification and treatment of epidural neoplasm, before the development of significant ne... more Early identification and treatment of epidural neoplasm, before the development of significant neurologic deficits, provides the best opportunity for a favorable outcome. Among the many patients with symptoms, signs, or scintigraphic or radiographic findings suggesting possible epidural disease, a small proportion will have the lesion. The selection of patients for definitive imaging of the epidural space should be based on a determination of the risk of this complication. In this study, the medical records, plain spinal radiographs, bone scintigraphs and myelograms of 43 patients were analyzed retrospectively to assess the risk of epidural disease associated with specific clinical, radiographic, and scintigraphic findings. Cervical, thoracic, and lumbosacral spinal segments were evaluated independently. Symptomatic segments (SS) (N = 41), defined by focal pain or neurologic dysfunction, were distinguished from asymptomatic segments (AS). At SS,,epidural disease was found at 86% and 8% of abnormal and normal spinal radiographs, respectively (P < 0.001), and at 69% and 0% of abnormal and normal scintigrams, respectively (P < 0.001), whereas at A S epidural disease occurred in 43% and 3% of abnormal and normal spinal radiographs, respectively (P < 0.001), and 14% and 7% of abnormal and normal scintigrams, respectively (P = NS).

Research paper thumbnail of Myocardial Ischemia Related to Ergot Alkaloids: A Case Report and Literature Review

Headache: The Journal of Head and Face Pain, 1991

Ergotamine tartrate and methysergide are widely used headache treatments with important vasoconst... more Ergotamine tartrate and methysergide are widely used headache treatments with important vasoconstrictive properties. We report a 31-year-old man with cluster headaches who developed severe, prolonged myocardial ischemia following combination therapy with ergotamine tartrate and methysergide. We reviewed the cardiovascular complications of each agent alone and in combination. Given the pharmacologic similarity of these agents, we propose that they may have additive or synergistic cardiac toxicity, at least in vulnerable individuals. We recommend caution when these agents are used together.

Research paper thumbnail of Quantitative Sensory Testing Demonstrates That Subclinical Sensory Neuropathy Is Prevalent in Patients With Cancer

Archives of Neurology, 1987

Vibration threshold (VT) determinations were used to assess the function of the large nerve-fiber... more Vibration threshold (VT) determinations were used to assess the function of the large nerve-fiber sensory system in 171 patients with cancer and 58 healthy subjects. Significant differences in VT indicate dysfunction of this sensory system in the cancer group. Twelve percent of the cancer patients had elevated VT compared with 1.7% of control subjects. Elevated VT was not associated with risk factors for neuropathy such as diabetes, renal disease, poor nutrition, or treatment with chemotherapy. Although VT elevation was associated with alcoholism and increasing age, these variables accounted for only a small proportion of the variance in VT. These data suggest that VT determinations are a useful method for quantifying sensory abnormalities in cancer patients. Sensory abnormalities occur in a significant proportion of patients with cancer and seem to be related directly to the neoplasm, rather than to known risk factors for neuropathy.

Research paper thumbnail of Randomized Controlled Study of Telcagepant Plus Ibuprofen or Acetaminophen in Migraine

Headache: The Journal of Head and Face Pain, 2011

To evaluate the efficacy and tolerability of telcagepant when co-administered with ibuprofen or a... more To evaluate the efficacy and tolerability of telcagepant when co-administered with ibuprofen or acetaminophen for the acute treatment of migraine. Telcagepant is an oral calcitonin gene-related peptide receptor antagonist which is being evaluated for the acute treatment of migraine. Combining telcagepant with analgesics that have a different mechanism of action could produce greater efficacy. Randomized, double-blind, placebo-controlled study. Patients were randomized to treat a moderate or severe migraine headache with either telcagepant 280 mg + ibuprofen 400 mg (N = 171), telcagepant 280 mg + acetaminophen 1000 mg (N = 171), telcagepant 280 mg (N =170), or placebo (N = 171). The primary efficacy endpoint was 2-hour pain freedom. The study had approximately 88% power to detect an additive effect of at least 15 percentage points (telcagepant combination vs telcagepant monotherapy) and 48% power to detect an additive effect of at least 10 percentage points. Safety and tolerability were assessed by adverse events and laboratory tests. The percentages of patients with 2-hour pain freedom were greater in each active treatment group compared to placebo (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001): telcagepant + ibuprofen = 35.2%, telcagepant + acetaminophen = 38.3%, telcagepant = 31.2%, placebo = 10.9%. No significant differences were seen for either of the combination groups vs telcagepant monotherapy, but both were numerically larger than telcagepant monotherapy. All the active treatments were generally well tolerated. The percentage of patients reporting any adverse event within 48 hours was higher in the active treatment groups than placebo: telcagepant + ibuprofen = 30.3%, telcagepant + acetaminophen = 31.6%, telcagepant = 24.8%, placebo = 18.2%. The most common adverse events reported by ≥ 4 patients in one or more of the treatment groups that included telcagepant were fatigue, nausea, dizziness, somnolence, dry mouth, and tremor. The combination of telcagepant 280 mg with either ibuprofen 400 mg or acetaminophen 1000 mg did not show a statistically significant difference from telcagepant alone. Numerically greater treatment effects in the combination treatment groups over the telcagepant 280 mg monotherapy suggest that telcagepant combination treatments may merit further evaluation in studies powered to detect smaller additive benefits. (Clinicaltrials.gov; NCT00758836).

Research paper thumbnail of Topiramate Treatment of Chronic Migraine: A Randomized, Placebo-Controlled Trial of Quality of Life and Other Efficacy Measures

Headache: The Journal of Head and Face Pain, 2009

Objective.-To define yet more clearly the utility of topiramate in the treatment of chronic migra... more Objective.-To define yet more clearly the utility of topiramate in the treatment of chronic migraine, we evaluated prespecified secondary endpoints from a recent randomized, double-blind, placebo-controlled, multicenter clinical trial.

Research paper thumbnail of Estimating episodic memory within-subject decline among nondemented older adults: Results from the einstein aging study (EAS)

Alzheimer's & Dementia, 2015

Research paper thumbnail of Very Mild Dementia and Medical Comorbidity Independently Predict Health Care Use in the Elderly

Journal of Primary Care & Community Health, 2012

Research paper thumbnail of Screening Older Latinos for Dementia in the Primary Care Setting

Journal of the International Neuropsychological Society, 2014

The purpose was to compare the Spanish language picture version of the Free and Cued Selective Re... more The purpose was to compare the Spanish language picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT + IR) and the Mini Mental State Exam (MMSE) in identifying very mild dementia among Spanish speaking Latino patients. The tests and an independent diagnostic assessment were administered to 112 Latino patients free of medically diagnosed dementia from an urban primary care clinic. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to examine differences in the operating characteristics of the pFCSRT + IR and the MMSE. Cut scores were manipulated to equate sensitivities (specificities) at clinically relevant values to compare differences in specificities (sensitivities) using the Pearson Chi Square test. Youden's index was used to select the optimal cut scores. Twenty-four of the 112 primary care patients (21%) received a research dementia diagnosis, indicating a substantial burden of unrecognized dementia. MMSE scores but not free recall scores were associated with years of education in patients free of dementia. AUC was significantly higher for free recall than for MMSE. Free recall performed significantly better than the MMSE in sensitivity and in specificity. Using optimal cut scores, patients with impaired free recall were 10 times more likely to have dementia than patients with intact recall, and patients with impaired MMSE scores were 4.5 times more likely to have dementia than patients with intact scores. These results suggest that the Spanish language pFCSRT + IR may be an effective tool for dementia screening in educationally diverse Latino primary care populations. (JINS, 2014, 20, 848-855)

Research paper thumbnail of Conventional and robust norming in identifying preclinical dementia

Journal of Clinical and Experimental Neuropsychology, 2015

To contrast four approaches to norming two widely used memory tests in older adults for the purpo... more To contrast four approaches to norming two widely used memory tests in older adults for the purpose of detecting preclinical dementia. The study sample included participants from the Einstein Aging Study who were over age 70, were free of dementia at baseline, and were followed for at least 5 years. Norms were derived from a conventional sample (excluding individuals with dementia at baseline but not those who developed dementia during follow-up) and a robust normative sample (excluding persons with dementia at baseline as well as those who developed dementia over 5 years of follow-up). Both normative samples were examined with and without adjustment for age and education. We contrasted the picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT+IR) and the Logical Memory (LM) test for their ability to identify persons with preclinical dementia, operationally defined by the development of diagnosable dementia over 5 years of follow-up, using these four approaches to developing norms for detecting preclinical dementia. Of 418 participants included in the conventional normative sample, the mean age was 78.2 years, and 59% were female. There were 78 incident cases of dementia over 5 years leaving 340 participants in the robust normative sample. Means and standard deviations were defined for both the conventional and robust normative samples, and cut-scores with and without adjustment were set at 1.5 standard deviations below the mean of each test. As predicted, in comparison with the conventional sample, the robust sample had higher cut-scores, which provided higher sensitivity for detecting preclinical dementia. This effect persisted regardless of adjustment. The pFCSRT+IR was more sensitive than LM in detecting incident dementia cases. When using cognitive test norms to identify preclinical dementia, robust norming procedures improves detection using both the pFCSRT+IR and LM.

Research paper thumbnail of Amyloid Burden Determined by Image Analysis Correlates With Conventional Histochemical Methods and Clinical Measures of Cognitive Decline

Journal of Neuropathology and Experimental Neurology

Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home &amp;gt; May ...

Research paper thumbnail of Memory impairment, executive dysfunction, and intellectual decline in preclinical Alzheimer's disease

Journal of the International Neuropsychological Society, 2008

In the Baltimore Longitudinal Study of Aging (BLSA), we examined the temporal unfolding of declin... more In the Baltimore Longitudinal Study of Aging (BLSA), we examined the temporal unfolding of declining performance on tests of episodic memory (Free Recall on the Free and Cued Selective Reminding Test), executive function (Category Fluency, Letter Fluency, and Trails), and Verbal Intelligence ; American Version of the Nelson Adult Reading Test [AMNART]) before the diagnosis of dementia in 92 subjects with incident Alzheimer's disease (AD) followed for up to 15 years before diagnosis. To examine the preclinical onset of cognitive decline, we aligned subjects at the time of initial AD diagnosis and examined the cognitive course preceding diagnosis. We found that declines in performance on tests of episodic memory accelerated 7 years before diagnosis. Declining performance on tests of executive function accelerated 2-3 years before diagnosis, and verbal intelligence declined in close proximity to diagnosis. This cognitive profile is compatible with pathologic data suggesting that structures which mediate memory are affected earlier than frontal structures during the preclinical onset of AD. It also supports the view that VIQ as estimated by the AMNART does not decline during the preclinical onset of AD.

Research paper thumbnail of Nonpharmacologic Treatments for Migraine and Tension-Type Headache: How to Choose and When to Use

Current Treatment Options in Neurology, 2010

There are a variety of nonpharmacologic treatments for headache. Educating patients about headach... more There are a variety of nonpharmacologic treatments for headache. Educating patients about headache and its management, identifying and managing triggers (via diaries), modifying lifestyles, and understanding the importance of adopting and adhering to interventions (either pharmacologic or nonpharmacologic) are relevant to all persons with headache. In addition, specific nonpharmacologic treatments can be used either alone or in conjunction with ongoing pharmacologic intervention. Strong candidates for nonpharmacologic treatment include individuals with significant headache-related disability, comorbid mood or anxiety disorders, difficulty managing stress or other triggers, medication overuse, and patients who prefer a specific treatment. Behavioral treatments (relaxation, biofeedback, and cognitive-behavioral therapy) possess the most evidence for successful headache management. They have a long history of randomized trials showing efficacy and are considered first-line preventive options. Among complementary and alternative treatments, recent positive findings from randomized trials using acupuncture provide evidence of its potential as a first-line intervention. Other complementary and alternative techniques do not have a consistent base of research to recommend them for headache prevention, but they may be used if the patient prefers this approach or when other first-line interventions (nonpharmacologic or pharmacologic) have not provided adequate results. Among "natural" treatments, both butterbur extract and vitamin B2 have shown efficacy in more than one randomized trial and are thus potentially useful firstline preventive interventions.

Research paper thumbnail of Headache prevention outcome and body mass index

Cephalalgia, 2006

A population-based longitudinal study suggests that obesity is a strong risk factor for the devel... more A population-based longitudinal study suggests that obesity is a strong risk factor for the development of headaches on 15 or more days per month. Little is know about the influence of weight on the response to headache preventive treatment. Herein we prospectively assessed the influence of the baseline body mass index (BMI) on the response to headache preventive treatment. We included adults with episodic or chronic migraine (ICHD-2), or transformed migraine (Silberstein and Lipton criteria) that sought care in a headache clinic. BMI was assessed in the first visit. Baseline information included headache frequency, number of days with severe headache (prospectively obtained over 1 month), and headache-related disability (HIT-6). The same information was obtained after 3 months of preventive treatment. Subjects were categorized based on BMI in: normal weight ( ≤ 24.9), overweight (25-29.9), or obese ( ≥ 30). We contrasted the headache end-points using ANOVA with post-test and Kruskal-Wallis with post-test. We used logistic regression to model BMI and headache parameters adjusting for covariates. Our sample consisted of 176 subjects (79.5% women, mean of 44.4 years). At baseline 40.9% had normal weight, 29.5% were overweight and 27.3% were obese. No significant differences were observed in the number of headache days at baseline. After treatment, frequency declined in the entire population, but no significant differences were found by BMI group. Regarding the number of days with severe pain per month, there were also no significant differences at baseline (normal = 6.1, overweight = 6.5, obese = 6.7), and improvement overall ( P = 0.01). However, changes were greater in the obese (reduction in 2.7 days with treatment) and overweight (3.9) vs. normal (1.5, P < 0.01). Finally, HIT scores at baseline did not differ by BMI group (normal weight = 63.8, overweight = 64.1, obese = 63.6). However, compared with the normal weighted group, change in HIT scores (followup baseline) were greater in the obese (6.4 vs. 3.5, P < 0.05) and overweight groups (6.8 vs. 3.5, P < 0.05). In the logistic regression model, BMI did not account for changes in disability, headache frequency, or in the number of days with severe headache per month, after adjusting for covariates. Contrary to what we hypothesized, obesity at baseline does not seem to be related to follow-up refractoriness to preventive treatment. ᮀ Migraine, preventive treatment, obesity, body mass index

Research paper thumbnail of Mitochondrial Dysfunction and MigraineEvidence and Hypotheses

Cephalalgia, 2006

The molecular basis of migraine is still not completely understood. An impairment of mitochondria... more The molecular basis of migraine is still not completely understood. An impairment of mitochondrial oxidative metabolism might play a role in the pathophysiology of this disease, by influencing neuronal information processing. Biochemical assays of platelets and muscle biopsies performed in migraine sufferers have shown a decreased activity of the respiratory chain enzymes. Studies with phosphorus magnetic resonance spectroscopy ( 31 P-MRS) have demonstrated an impairment of the brain oxidative energy metabolism both during and between migraine attacks. However, molecular genetic studies have not detected specific mitochondrial DNA (mtDNA) mutations in patients with migraine, although other studies suggest that particular genetic markers (i.e. neutral polymorphisms or secondary mtDNA mutations) might be present in some migraine sufferers. Further studies are still needed to clarify if migraine is associated with unidentified mutations on the mtDNA or on nuclear genes that code mitochondrial proteins. In this paper, we review morphological, biochemical, imaging and genetic studies which bear on the hypothesis that migraine may be related to mitochondrial dysfunction at least in some individuals. ᮀ Brain oxidative metabolism, magnetic resonance spectroscopy, migraine, mitochondrial dysfunction, mutation

Research paper thumbnail of Identification of epidural neoplasm. Radiography and bone scintigraphy in the symptomatic and asymptomatic spine

Cancer, 1989

Early identification and treatment of epidural neoplasm, before the development of significant ne... more Early identification and treatment of epidural neoplasm, before the development of significant neurologic deficits, provides the best opportunity for a favorable outcome. Among the many patients with symptoms, signs, or scintigraphic or radiographic findings suggesting possible epidural disease, a small proportion will have the lesion. The selection of patients for definitive imaging of the epidural space should be based on a determination of the risk of this complication. In this study, the medical records, plain spinal radiographs, bone scintigraphs and myelograms of 43 patients were analyzed retrospectively to assess the risk of epidural disease associated with specific clinical, radiographic, and scintigraphic findings. Cervical, thoracic, and lumbosacral spinal segments were evaluated independently. Symptomatic segments (SS) (N = 41), defined by focal pain or neurologic dysfunction, were distinguished from asymptomatic segments (AS). At SS,,epidural disease was found at 86% and 8% of abnormal and normal spinal radiographs, respectively (P < 0.001), and at 69% and 0% of abnormal and normal scintigrams, respectively (P < 0.001), whereas at A S epidural disease occurred in 43% and 3% of abnormal and normal spinal radiographs, respectively (P < 0.001), and 14% and 7% of abnormal and normal scintigrams, respectively (P = NS).

Research paper thumbnail of Myocardial Ischemia Related to Ergot Alkaloids: A Case Report and Literature Review

Headache: The Journal of Head and Face Pain, 1991

Ergotamine tartrate and methysergide are widely used headache treatments with important vasoconst... more Ergotamine tartrate and methysergide are widely used headache treatments with important vasoconstrictive properties. We report a 31-year-old man with cluster headaches who developed severe, prolonged myocardial ischemia following combination therapy with ergotamine tartrate and methysergide. We reviewed the cardiovascular complications of each agent alone and in combination. Given the pharmacologic similarity of these agents, we propose that they may have additive or synergistic cardiac toxicity, at least in vulnerable individuals. We recommend caution when these agents are used together.

Research paper thumbnail of Quantitative Sensory Testing Demonstrates That Subclinical Sensory Neuropathy Is Prevalent in Patients With Cancer

Archives of Neurology, 1987

Vibration threshold (VT) determinations were used to assess the function of the large nerve-fiber... more Vibration threshold (VT) determinations were used to assess the function of the large nerve-fiber sensory system in 171 patients with cancer and 58 healthy subjects. Significant differences in VT indicate dysfunction of this sensory system in the cancer group. Twelve percent of the cancer patients had elevated VT compared with 1.7% of control subjects. Elevated VT was not associated with risk factors for neuropathy such as diabetes, renal disease, poor nutrition, or treatment with chemotherapy. Although VT elevation was associated with alcoholism and increasing age, these variables accounted for only a small proportion of the variance in VT. These data suggest that VT determinations are a useful method for quantifying sensory abnormalities in cancer patients. Sensory abnormalities occur in a significant proportion of patients with cancer and seem to be related directly to the neoplasm, rather than to known risk factors for neuropathy.

Research paper thumbnail of Randomized Controlled Study of Telcagepant Plus Ibuprofen or Acetaminophen in Migraine

Headache: The Journal of Head and Face Pain, 2011

To evaluate the efficacy and tolerability of telcagepant when co-administered with ibuprofen or a... more To evaluate the efficacy and tolerability of telcagepant when co-administered with ibuprofen or acetaminophen for the acute treatment of migraine. Telcagepant is an oral calcitonin gene-related peptide receptor antagonist which is being evaluated for the acute treatment of migraine. Combining telcagepant with analgesics that have a different mechanism of action could produce greater efficacy. Randomized, double-blind, placebo-controlled study. Patients were randomized to treat a moderate or severe migraine headache with either telcagepant 280 mg + ibuprofen 400 mg (N = 171), telcagepant 280 mg + acetaminophen 1000 mg (N = 171), telcagepant 280 mg (N =170), or placebo (N = 171). The primary efficacy endpoint was 2-hour pain freedom. The study had approximately 88% power to detect an additive effect of at least 15 percentage points (telcagepant combination vs telcagepant monotherapy) and 48% power to detect an additive effect of at least 10 percentage points. Safety and tolerability were assessed by adverse events and laboratory tests. The percentages of patients with 2-hour pain freedom were greater in each active treatment group compared to placebo (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001): telcagepant + ibuprofen = 35.2%, telcagepant + acetaminophen = 38.3%, telcagepant = 31.2%, placebo = 10.9%. No significant differences were seen for either of the combination groups vs telcagepant monotherapy, but both were numerically larger than telcagepant monotherapy. All the active treatments were generally well tolerated. The percentage of patients reporting any adverse event within 48 hours was higher in the active treatment groups than placebo: telcagepant + ibuprofen = 30.3%, telcagepant + acetaminophen = 31.6%, telcagepant = 24.8%, placebo = 18.2%. The most common adverse events reported by ≥ 4 patients in one or more of the treatment groups that included telcagepant were fatigue, nausea, dizziness, somnolence, dry mouth, and tremor. The combination of telcagepant 280 mg with either ibuprofen 400 mg or acetaminophen 1000 mg did not show a statistically significant difference from telcagepant alone. Numerically greater treatment effects in the combination treatment groups over the telcagepant 280 mg monotherapy suggest that telcagepant combination treatments may merit further evaluation in studies powered to detect smaller additive benefits. (Clinicaltrials.gov; NCT00758836).

Research paper thumbnail of Topiramate Treatment of Chronic Migraine: A Randomized, Placebo-Controlled Trial of Quality of Life and Other Efficacy Measures

Headache: The Journal of Head and Face Pain, 2009

Objective.-To define yet more clearly the utility of topiramate in the treatment of chronic migra... more Objective.-To define yet more clearly the utility of topiramate in the treatment of chronic migraine, we evaluated prespecified secondary endpoints from a recent randomized, double-blind, placebo-controlled, multicenter clinical trial.

Research paper thumbnail of Estimating episodic memory within-subject decline among nondemented older adults: Results from the einstein aging study (EAS)

Alzheimer's & Dementia, 2015

Research paper thumbnail of Very Mild Dementia and Medical Comorbidity Independently Predict Health Care Use in the Elderly

Journal of Primary Care & Community Health, 2012

Research paper thumbnail of Screening Older Latinos for Dementia in the Primary Care Setting

Journal of the International Neuropsychological Society, 2014

The purpose was to compare the Spanish language picture version of the Free and Cued Selective Re... more The purpose was to compare the Spanish language picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT + IR) and the Mini Mental State Exam (MMSE) in identifying very mild dementia among Spanish speaking Latino patients. The tests and an independent diagnostic assessment were administered to 112 Latino patients free of medically diagnosed dementia from an urban primary care clinic. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to examine differences in the operating characteristics of the pFCSRT + IR and the MMSE. Cut scores were manipulated to equate sensitivities (specificities) at clinically relevant values to compare differences in specificities (sensitivities) using the Pearson Chi Square test. Youden's index was used to select the optimal cut scores. Twenty-four of the 112 primary care patients (21%) received a research dementia diagnosis, indicating a substantial burden of unrecognized dementia. MMSE scores but not free recall scores were associated with years of education in patients free of dementia. AUC was significantly higher for free recall than for MMSE. Free recall performed significantly better than the MMSE in sensitivity and in specificity. Using optimal cut scores, patients with impaired free recall were 10 times more likely to have dementia than patients with intact recall, and patients with impaired MMSE scores were 4.5 times more likely to have dementia than patients with intact scores. These results suggest that the Spanish language pFCSRT + IR may be an effective tool for dementia screening in educationally diverse Latino primary care populations. (JINS, 2014, 20, 848-855)

Research paper thumbnail of Conventional and robust norming in identifying preclinical dementia

Journal of Clinical and Experimental Neuropsychology, 2015

To contrast four approaches to norming two widely used memory tests in older adults for the purpo... more To contrast four approaches to norming two widely used memory tests in older adults for the purpose of detecting preclinical dementia. The study sample included participants from the Einstein Aging Study who were over age 70, were free of dementia at baseline, and were followed for at least 5 years. Norms were derived from a conventional sample (excluding individuals with dementia at baseline but not those who developed dementia during follow-up) and a robust normative sample (excluding persons with dementia at baseline as well as those who developed dementia over 5 years of follow-up). Both normative samples were examined with and without adjustment for age and education. We contrasted the picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT+IR) and the Logical Memory (LM) test for their ability to identify persons with preclinical dementia, operationally defined by the development of diagnosable dementia over 5 years of follow-up, using these four approaches to developing norms for detecting preclinical dementia. Of 418 participants included in the conventional normative sample, the mean age was 78.2 years, and 59% were female. There were 78 incident cases of dementia over 5 years leaving 340 participants in the robust normative sample. Means and standard deviations were defined for both the conventional and robust normative samples, and cut-scores with and without adjustment were set at 1.5 standard deviations below the mean of each test. As predicted, in comparison with the conventional sample, the robust sample had higher cut-scores, which provided higher sensitivity for detecting preclinical dementia. This effect persisted regardless of adjustment. The pFCSRT+IR was more sensitive than LM in detecting incident dementia cases. When using cognitive test norms to identify preclinical dementia, robust norming procedures improves detection using both the pFCSRT+IR and LM.

Research paper thumbnail of Amyloid Burden Determined by Image Analysis Correlates With Conventional Histochemical Methods and Clinical Measures of Cognitive Decline

Journal of Neuropathology and Experimental Neurology

Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home &amp;gt; May ...

Research paper thumbnail of Memory impairment, executive dysfunction, and intellectual decline in preclinical Alzheimer's disease

Journal of the International Neuropsychological Society, 2008

In the Baltimore Longitudinal Study of Aging (BLSA), we examined the temporal unfolding of declin... more In the Baltimore Longitudinal Study of Aging (BLSA), we examined the temporal unfolding of declining performance on tests of episodic memory (Free Recall on the Free and Cued Selective Reminding Test), executive function (Category Fluency, Letter Fluency, and Trails), and Verbal Intelligence ; American Version of the Nelson Adult Reading Test [AMNART]) before the diagnosis of dementia in 92 subjects with incident Alzheimer's disease (AD) followed for up to 15 years before diagnosis. To examine the preclinical onset of cognitive decline, we aligned subjects at the time of initial AD diagnosis and examined the cognitive course preceding diagnosis. We found that declines in performance on tests of episodic memory accelerated 7 years before diagnosis. Declining performance on tests of executive function accelerated 2-3 years before diagnosis, and verbal intelligence declined in close proximity to diagnosis. This cognitive profile is compatible with pathologic data suggesting that structures which mediate memory are affected earlier than frontal structures during the preclinical onset of AD. It also supports the view that VIQ as estimated by the AMNART does not decline during the preclinical onset of AD.

Research paper thumbnail of Nonpharmacologic Treatments for Migraine and Tension-Type Headache: How to Choose and When to Use

Current Treatment Options in Neurology, 2010

There are a variety of nonpharmacologic treatments for headache. Educating patients about headach... more There are a variety of nonpharmacologic treatments for headache. Educating patients about headache and its management, identifying and managing triggers (via diaries), modifying lifestyles, and understanding the importance of adopting and adhering to interventions (either pharmacologic or nonpharmacologic) are relevant to all persons with headache. In addition, specific nonpharmacologic treatments can be used either alone or in conjunction with ongoing pharmacologic intervention. Strong candidates for nonpharmacologic treatment include individuals with significant headache-related disability, comorbid mood or anxiety disorders, difficulty managing stress or other triggers, medication overuse, and patients who prefer a specific treatment. Behavioral treatments (relaxation, biofeedback, and cognitive-behavioral therapy) possess the most evidence for successful headache management. They have a long history of randomized trials showing efficacy and are considered first-line preventive options. Among complementary and alternative treatments, recent positive findings from randomized trials using acupuncture provide evidence of its potential as a first-line intervention. Other complementary and alternative techniques do not have a consistent base of research to recommend them for headache prevention, but they may be used if the patient prefers this approach or when other first-line interventions (nonpharmacologic or pharmacologic) have not provided adequate results. Among "natural" treatments, both butterbur extract and vitamin B2 have shown efficacy in more than one randomized trial and are thus potentially useful firstline preventive interventions.