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Biomedical subjects

R B Lipton

Publications and source records attributed to R B Lipton.

At least 19 recordsLinked to original sources
PubMed2006

A genotype of exceptional longevity is associated with preservation of cognitive function.

OBJECTIVE: To test whether cholesterol ester transfer protein (CETP) genotype (VV homozygosity for I405V) is associated with preservation of cognitive function in addition to its association with exceptional longevity. METHODS: We studied Ashkenazi Jews with exceptional longevity (n = 158; age 99.2 +/- 0.3 years) for the associations of CETP VV genotype and lipoprotein phenotype, using the Mini-Mental State Examination (MMSE). To confirm the role of CETP in a younger cohort, we studied subjects from the Einstein Aging Study (EAS) for associations between CETP VV and cognitive impairment. RESULTS: Subjects with MMSE > 25 were twice as likely to have the CETP VV genotype (29% vs 14%, p = 0.02), and those with the VV genotype were more likely (61% vs 30%, p = 0.02) to have MMSE > 25. Subjects with the VV genotype had lower levels of CETP (1.73 +/- 0.11 vs 2.12 +/- 0.10 mug/mL, p = 0.01), higher high-density lipoprotein (HDL) levels (p = 0.02), and larger lipoprotein particles (p = 0.03). In the EAS cohort, an approximately fivefold increase in the VV genotype (21% vs 4%, p = 0.02), higher HDL levels, and larger lipoprotein particle sizes were associated with less dementia and improved memory. CONCLUSIONS: Using two independent cohorts, we implicate the longevity CETP gene as a modulator of age-related cognitive function. A specific CETP genotype is associated with lower CETP levels and a favorable lipoprotein profile. It has not been determined whether modulation of this gene prevents age-related decline or AD.

Age Distribution↗
PubMed2006

Incidence of epilepsy in a racially diverse, community-dwelling, elderly cohort: results from the Einstein aging study.

OBJECTIVE: To determine age-specific incidence and cumulative incidence of epilepsy in a well-defined cohort of elderly people, and to examine how rates of epilepsy are modified by sex, race, stroke, dementia, head injury, and depression. METHODS: The authors examined data from a reconstructed cohort based on 1919 community-dwelling volunteers, followed as part of a large ongoing prospective aging study. RESULTS: Age-specific incidence was 10.6 (per 100,000 person-years) between ages 45 and 59, 25.8 between ages 60 and 74, and 101.1 between ages 75 and 89. Cumulative incidence was 0.15% from age 45 to age 60, 0.38% to age 70, 1.01% to age 80, and 1.47% to age 90. In addition, the difference in cumulative incidence among African-American subjects approached statistical significance (57.6/100,000 person-years versus 26.1 in Caucasian, p=0.10), and the difference in incidence among subjects reporting a history of stroke was significantly elevated (p=0.029). Incidence of epilepsy was not statistically elevated among males, those with dementia, or individuals reporting a history of head injury or treatment for depression. Among "healthy" subjects without history of stroke, head injury, or dementia, we observed a cumulative risk of epilepsy with onset after age 60 of only 1.1%. CONCLUSIONS: The incidence of epilepsy was low in this relatively healthy cohort of elderly people, especially among subjects without known risk factors. In this study we identified African-American race as a risk factor in the elderly for epilepsy independent of stroke.

Black or African American↗
PubMed2006

Familial risk of migraine: variation by proband age at onset and headache severity.

BACKGROUND: It is well established that migraine aggregates within families. Less is known about the influence of proband characteristics (e.g., age at onset, headache severity) on familial aggregation. OBJECTIVE: To examine the association between the proband's migraine severity and age at migraine onset and familial aggregation of migraine. METHODS: The authors investigated the migraine prevalence in first-degree relatives of 532 persons with migraine and control subjects in a population study. Familial aggregation was expressed as the risk of migraine in family members of probands divided by risk in control family members. RESULTS: The relative risk (RR) of migraine in first-degree relatives of migraine probands was elevated compared with family members of controls (RR = 1.88; 95% CI: 1.30 to 2.72). The RR was also significantly higher for relatives of probands reporting onset of migraine before age 16 (2.50; 95% CI: 1.65 to 3.79) compared with those with onset at age 16 or older (1.44; 95% CI: 0.93 to 2.23). Among probands with very severe average pain scores (i.e., 9 to 10 on a 0 to 10 scale), the RR of migraine in family members was 2.38 (95% CI: 1.56 to 3.62) compared with 1.52 (0.99 to 2.34) for less severe pain (p < 0.05). CONCLUSION: Early onset of migraine in the proband as well as the severity of migraines are associated with higher levels of family aggregation.

Adult↗
PubMed2006

Leisure activities and the risk of amnestic mild cognitive impairment in the elderly.

OBJECTIVE: To study the influence of leisure activity participation on risk of development of amnestic mild cognitive impairment (aMCI). METHODS: The authors examined the relationship between baseline level of participation in leisure activities and risk of aMCI in a prospective cohort of 437 community-residing subjects older than 75 years, initially free of dementia or aMCI, using Cox analysis adjusted for age, sex, education, and chronic illnesses. The authors derived Cognitive and Physical Activity Scales based on frequency of participation in individual activities. RESULTS: Over a median follow-up of 5.6 years, 58 subjects had development of aMCI. A one-point increase on the Cognitive (hazard ratio [HR] 0.95, 95% CI 0.91 to 0.99) but not Physical Activities Scale (HR 0.97, 95% CI 0.93 to 1.01) was associated with lower risk of aMCI. Subjects with Cognitive Activity scores in the highest (HR 0.46, 95% CI 0.24 to 0.91) and middle thirds (HR 0.52, 95% CI 0.29 to 0.96) had a lower risk of aMCI compared with subjects in the lowest third. The association persisted even after excluding subjects who converted to dementia within 2 years of meeting criteria for aMCI. CONCLUSIONS: Cognitive activity participation is associated with lower risk of development of amnestic mild cognitive impairment, even after excluding individuals at early stages of dementia.

Aged↗
PubMed2006

Patterns of medical diagnosis and treatment of migraine and probable migraine in a health plan.

The objectives of this study were to assess the proportion of subjects with strict migraine (SM, migraine with and without aura), probable migraine (PM), and all migraine (AM, SM and PM pooled together), who receive a medical diagnosis or a specific treatment within a health plan. Eligible participants were 18-55-year participants of a non-profit health maintenance organization (HMO) who had received out-patient, emergency department, or in-patient care from a physician within the past year. We used a validated computer-assisted telephone interview (CATI) survey to identify SM, PM and controls (received out-patient, emergency department, or in-patient care from a physician for any reason within the past year, but did not have SM or PM). Medical and prescription drug claims for the 24-month period were linked to participant files. Among 8579 respondents, we identified 1265 SM sufferers and 1252 PM sufferers, which were compared with 960 randomly selected controls. Just 194 (15.3%) SM, 21 (1.7%) PM, and 215 (8.5%) AM sufferers received an in-patient or out-patient primary migraine claim in the previous 24 months, compared with six (0.5%) controls; 240 (18.9%) SM, 39 (3.1%) PM, 279 (11.1%) AM sufferers, and eight controls (0.6%) received any migraine claim. There were claims for migraine drugs (ICD-9 code for triptans or ergot compounds) for just 140 (11.1%) SM and 34 (2.7%) PM sufferers, and migraine analgesics (butalbital and isomethepthene compounds), for 6.3% SM and 2.2% PM sufferers (0.7% of the controls). Migraine preventives were used for a larger number of SM and PM sufferers (19.6% and 13.1%), but also for controls (10.5%), indicating that they were probably used for other medical reasons. Both SM and PM are underdiagnosed and undertreated within a health plan. Educational strategies should focus on physician education addressing diagnosing the full spectrum of migraine and physician management of migraine with specific migraine therapy in appropriate patients.

Adolescent↗
PubMed2006

Headache prevention outcome and body mass index.

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 (follow-up 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.

Adolescent↗
PubMed2006

Mitochondrial dysfunction and migraine: evidence and hypotheses.

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.

Animals↗
PubMed2006

Field testing alternative criteria for chronic migraine.

The criteria for chronic migraine (CM), as proposed by the Second Edition of the International Classification of Headache Disorders (ICHD-2) is very restrictive, excluding most patients that evolve from episodic migraine. In this study we empirically tested three recent proposals for revised criteria for CM. We included individuals with transformed migraine (TM) with or without medication overuse, according to the criteria proposed by Silberstein and Lipton. All individuals had headache calendars for at least three consecutive months. We assessed the proportion of subjects that fulfilled ICHD-2 criteria for CM or probable chronic migraine with probable medication overuse (CM+). We also tested three proposals for making the CM criteria more inclusive. In proposal 1, CM/CM + would require at least 15 days of migraine or probable migraine per month. Proposal 2 suggests that CM/CM + would be classified in those with >or= 15 days of headache per month, where at least 50% of these days are migraine or probable migraine. Proposal 3 suggests that CM/CM + would be classified in those with chronic daily headache and at least 8 days of migraine or probable migraine per month. Among TM sufferers, 399 (62.5%) had TM with medication overuse, and just 10.2% were classified as CM+ 158 (37.5%) had TM without medication overuse; just nine (5.6%) met current ICHD-2 criteria for CM. Using the alternative criteria, proposal 1 included 48.7% of patients with TM without medication overuse; proposal 2 captured 88%, and proposal 3 classified 94.9% of these patients. For TM with medication overuse, the proportions for proposals 1-3 were, respectively, 37%, 81% and 91%. The differences were statistically significant, favouring proposal 3. Consistently, criteria for CM and CM+ should be revised to require at least 8 days of migraine or probable migraine per month, in individuals with 15 or more days of headache per month.

Adolescent↗
PubMed2006

New appendix criteria open for a broader concept of chronic migraine.

After the introduction of chronic migraine and medication overuse headache as diagnostic entities in The International Classification of Headache Disorders, Second Edition, ICHD-2, it has been shown that very few patients fit into the diagnostic criteria for chronic migraine (CM). The system of being able to use CM and the medication overuse headache (MOH) diagnosis only after discontinuation of overuse has proven highly unpractical and new data have suggested a much more liberal use of these diagnoses. The International Headache Classification Committee has, therefore, worked out the more inclusive criteria for CM and MOH presented in this paper. These criteria are included in the appendix of ICHD-2 and are meant primarily for further scientific evaluation but may be used already now for inclusion into drug trials, etc. It is now recommended that the MOH diagnosis should no longer request improvement after discontinuation of medication overuse but should be given to patients if they have a primary headache plus ongoing medication overuse. The latter is defined as previously, i.e. 10 days or more of intake of triptans, ergot alkaloids mixed analgesics or opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than one substance. If these new criteria for CM and MOH prove useful in future testing, the plan is to include them in a future revised version of ICHD-2.

Chronic Disease↗
PubMed2006

Retinal migraine reappraised.

Retinal migraine is usually characterized by attacks of fully reversible monocular visual loss associated with migraine headache. Herein we summarize the clinical features and prognosis of 46 patients (six new cases and 40 from the literature) with retinal migraine based upon the International Classification of Headache Disorders-2 (ICHD-2) criteria. In our review, retinal migraine is most common in women in the second to third decade of life. Contrary to ICHD-2 criteria, most have a history of migraine with aura. In the typical attack monocular visual features consist of partial or complete visual loss lasting <1 h, ipsilateral to the headache. Nearly half of reported cases with recurrent transient monocular visual loss subsequently experienced permanent monocular visual loss. Although the ICHD-2 diagnostic criteria for retinal migraine require reversible visual loss, our findings suggest that irreversible visual loss is part of the retinal migraine spectrum, perhaps representing an ocular form of migrainous infarction. Based on this observation, the authors recommend migraine prophylactic treatment in an attempt to prevent permanent visual loss, even if attacks are infrequent. We also propose a revision to the ICHD-2 diagnostic criteria for retinal migraine.

Adolescent↗
PubMed2005

Clinical trials of acute treatments for migraine including multiple attack studies of pain, disability, and health-related quality of life.

Because migraine has features in common with episodic monophasic pain disorders (such as postoperative or posttraumatic pain) and with chronic pain disorders (such as osteoarthritis or painful neuropathy), it is often considered an episodic-chronic disorder. In clinical practice, the chronic aspects of migraine are addressed using preventive treatment strategies, while the episodic attacks are addressed by acute treatment strategies. Acute treatment strategies have generally been supported by clinical trial designs that focus on single attacks, whereas preventive treatment strategies evaluate multiple attacks over a period of time. Recently, long-term acute treatment clinical designs have emerged that may inform the design of clinical trials for other episodic-chronic disorders. After reviewing traditional acute treatment clinical trials, we focus here on study methods designed to evaluate treatment and management strategies for migraine over multiple attacks, including outcomes that assess the chronic-episodic nature of migraine (such as headache recurrence and consistency of relief), rather than relief from single attacks. We also discuss end points that reflect the treatment needs of patients, such as disability and health-related quality of life. The traditional randomized controlled trial designed to assess treatment efficacy for a single attack is insufficient to address the broader set of issues that arise in clinical practice. We consider clinical trials strategies designed to address the more complex clinical and policy requirements for meeting the needs of those with migraine.

Chronic Disease↗
PubMed2005

Chronic migraine is an earlier stage of transformed migraine in adults.

BACKGROUND: Chronic migraine (CM) is characterized by 15 or more migraine days per month. Most adults with chronic daily headache (CDH) that evolved from migraine have < 15 days of migraine/month. They are often classified as transformed migraine (TM), a disorder not addressed in the International Headache Society classification. OBJECTIVE: To test the hypothesis that early in the course of migraine chronification, the frequency of migraine attacks is high and that as illness progresses the frequency of nonmigraine headaches increases. METHODS: Information was collected on 402 adults with TM and was divided into two groups. Group 1 TM had > or = 15 days of migraine/month, whereas Group 2 TM had < 15 days of migraine/month. Risk factors were modeled for number of migraine days per month using logistic regression. RESULTS: Of 402 subjects with TM, 121 (30.1%) were in Group 1. The proportion of Group 1 subjects decreased with age, from 71% below age 30 to 22% age 60 or above. The correspondent proportion of Group 2 increased from 29 to 78%. More than 15 days of migraine per month was independently predicted by younger ages (< 40 years; p = 0.002), shorter interval from episodic to CDH (< 5 years; p = 0.003), and shorter time since the development of CDH (< 6 years; p < 0.0001). CONCLUSION: Chronic migraine is an earlier stage of transformed migraine.

Adolescent↗
PubMed2005

Identifying seizure clusters in patients with epilepsy.

Clinicians often encounter patients whose neurologic attacks appear to cluster. In a daily diary study, the authors explored whether clustering is a true phenomenon in epilepsy and can be identified in the clinical setting. Nearly half the subjects experienced at least one episode of three or more seizures in 24 hours; 20% also met a statistical clustering criterion. Utilizing the clinical definition of clustering should identify all seizure clusterers, and false positives can be determined with diary data.

Adult↗
PubMed2005

Dementia incidence may increase more slowly after age 90: results from the Bronx Aging Study.

BACKGROUND: Dementia incidence increases dramatically from age 65 to age 85, with many studies reporting a doubling every 5 years. The incidence beyond age 85 is not established. OBJECTIVE: To estimate the incidence of dementia as a function of age, with a particular focus on persons aged 85 and over. METHODS: The Bronx Aging Study began in 1980 with 488 healthy, nondemented community-dwelling individuals, age 75 to 85. Persons in the study received clinical examinations and cognitive testing approximately every 12 months until death or loss to follow-up. The diagnosis of dementia was made using Diagnostic and Statistical Manual of Mental Disorders-III-R at diagnostic case conferences. Dementia incidence rates were calculated for 5-year age bands using person-time of follow-up as the denominator. RESULTS: The relative incidence rate ratios of dementia for age 80 to 84 vs 75 to 79 was 2.32 (95% CI 1.23 to 4.37), the relative rate for age 85 to 89 vs 80 to 84 was 1.89 (95% CI 1.26 to 2.83), the relative rate for age 90 to 94 vs 85 to 89 was 1.49 (95% CI 0.86 to 2.58), while the relative rate for age 95 to 99 vs 90 to 94 was 1.31 (95% CI 0.38 to 4.46). Similar results were seen for men and women considered separately. Had the rate of increase from age 75 to 89 continued into the 90s, the study would have had 73% power to detect a significant difference between the rates for age 90 to 94 and 85 to 89 given the amount of observed follow-up time. CONCLUSIONS: Whereas dementia incidence continues to increase beyond age 85, the rate of increase appears to slow relative to that of 65- to 85-year-olds. These results suggest that dementia in the oldest old might be related not to the aging process itself but with age-associated risk factors.

Age Distribution↗
PubMed2005

A new screening tool for cervical dystonia.

BACKGROUND: Family studies of dystonia may be limited in part by small family size and incomplete ascertainment of dystonia in geographically dispersed families. Further, prevalence estimates of dystonia are believed to be underestimates, as most studies are clinic-based and many individuals do not present to a physician or are misdiagnosed. As a low-cost highly sensitive screening tool is needed to improve case detection for genetic and epidemiologic studies, the authors developed the Beth Israel Dystonia Screen (BIDS), a computer-assisted telephone interview. OBJECTIVE: To evaluate the validity and utility of a computer-assisted telephone interview in screening for cervical dystonia. METHODS: The BIDS was administered and videotaped neurologic examinations performed on 193 individuals from 16 families with cervical and cranial dystonia. With use of a final rating of definite dystonia, as determined by video review of a systematic neurologic evaluation, as the gold standard, the predictive value of a subset of questions from the BIDS was assessed. RESULTS: A positive response to at least two of five screening questions had a sensitivity for cervical dystonia of 100% and a specificity of 92%. With use of a positive response to three or more questions, definite dystonia was determined with 81% sensitivity and 97% specificity. CONCLUSIONS: The Beth Israel Dystonia Screen (BIDS) identifies cervical dystonia with excellent sensitivity and specificity in a family-based sample. The authors recommend the BIDS for family studies, but cross-validation in a population sample is advisable before applying this method to epidemiologic studies.

Adolescent↗
PubMed2005

The use of multiattribute decision models in evaluating triptan treatment options in migraine.

BACKGROUND: The physician treating patients with migraine is now able to choose from among seven triptans-almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan. These differ, to greater or lesser degrees, on a range of clinical attributes important for treatment selection. OBJECTIVE: To outline the basic principles of Multiattribute Decision Making (MADM) and describe how one such method-TOPSIS (Technique for Order Preference by Similarity to the Ideal Solution)-can be applied to evaluate the currently available triptans. METHODS: In an example application, summary data from a recent meta-analysis of 53 published and unpublished placebo-controlled trials of the oral triptans were combined in TOPSIS models with computer-generated attribute importance weights representing the entire range of possible values, That is, the relative performance of the triptans was explored across all logically possible combinations of relative importance of the treatment attributes available from the meta-analysis, and uncertainty was assessed based on the confidence intervals from the meta-analysis. RESULTS: When compared across the entire range of values for relative attribute importance, almotriptan, eletriptan and rizatriptan were more similar to a hypothetical ideal triptan and were more likely to appear in the top three closest to the hypothetical ideal, than were naratriptan, sumatriptan, and zolmitriptan. CONCLUSION: Using the TOPSIS model, almotriptan, eletriptan and rizatriptan were more likely to appear in the top three closest to the hypothetical ideal triptan.

Clinical Trials as Topic↗
PubMed2005

A trial of metoclopramide vs sumatriptan for the emergency department treatment of migraines.

OBJECTIVE: To compare the efficacy of 20 mg of IV metoclopramide, given up to four times over 2 hours as needed for persistent headache, with 6 mg of subcutaneous sumatriptan for the emergency department treatment of migraine headaches. METHODS: This was a randomized, double-blind, clinical trial with two intervention arms. The primary endpoint was change in pain intensity as measured by an 11-point pain scale at 2 hours. Secondary endpoints included change in pain intensity at 24 hours and rates of pain-free headache relief at 2 and 24 hours. RESULTS: Two hundred two patients were screened, and 78 of 91 eligible patients were randomized. The two groups had comparable pain scores at baseline. By 2 hours, the change in pain intensity for the metoclopramide group was 7.2 compared with 6.3 for the sumatriptan group (95% CI for difference: -0.2 to 2.2). When compared at 24 hours, the metoclopramide group had improved by 6.1 compared with baseline and the sumatriptan group had improved by 5.0 (95% CI for difference: -0.6 to 2.8). At 2 hours, pain-free rates were 59% in the metoclopramide arm and 35% in the sumatriptan arm (95% CI for difference of 24%: 2 to 46%). The most common side effects at both time points were weakness, dizziness, and drowsiness, which were distributed evenly between the two groups. There were no reports of chest pain within the first 2 hours. The incidence of restlessness, stiffness, and abnormal movements was distributed equally between the two groups. CONCLUSIONS: When compared at 2 and 24 hours, aggressive (20 mg dosed up to four times) IV metoclopramide and 6 mg of subcutaneous sumatriptan relieved migraine headache pain comparably. Some secondary endpoints suggest that metoclopramide may be the preferable therapy for migraines presenting to the emergency department.

Adult↗