Background

Type 2 diabetes has been associated with diminished late-life cognition; less is known about relations of insulin levels and insulin secretion to cognitive change among persons without diabetes. We examined prospectively relations of fasting insulin levels and insulin secretion to cognitive decline among healthy, community-dwelling older men without diabetes.

Methods

Fasting plasma insulin and C-peptide (insulin secretion) levels were measured in 1,353 nondiabetic men, aged 60–92 years (mean = 71.3 years), in the Physicians’ Health Study II, who participated in cognitive testing an average of 3.3 years later. Two assessments were administered 2 years apart (range = 1.5–4.0 years) using telephone-based tests (general cognition, verbal memory and category fluency). Primary outcomes were the Telephone Interview for Cognitive Status (TICS), global cognition (averaging all tests) and verbal memory (averaging 4 verbal tests). Multivariable linear regression models were used to estimate the relations of insulin and C-peptide to cognitive decline.

Results

Higher fasting insulin was associated with a greater decline on all tests, after adjustment. Findings were statistically significant for the TICS and category fluency, e.g. the multivariable-adjusted mean difference (95% CI) in decline for men with the highest versus lowest insulin levels was −0.62 (−1.15, −0.09) points on the TICS (p for trend = 0.04); this difference was similar to that between men 7 years apart in age. Similarly, there was a greater decline across all tests with increasing C-peptide, but the findings were statistically significant only for the global score (p for trend = 0.03).

Conclusions

Higher fasting insulin and greater insulin secretion in older men may be related to overall cognitive decline, even in the absence of diabetes.

Background

Type 2 diabetes has been associated with diminished late-life cognition; less is known about relations of insulin levels and insulin secretion to cognitive change among persons without diabetes. We examined prospectively relations of fasting insulin levels and insulin secretion to cognitive decline, among healthy, community-dwelling older men without diabetes.

Methods

Fasting plasma insulin and c-peptide (insulin secretion) levels were measured in 1,353 non-diabetic men, aged 60–92 years (mean=71.3), in the Physicians’ Health Study II who participated in cognitive testing an average of 3.3 years later. Two assessments were administered 2 years apart (range=1.5–4.0) using telephone-based tests (general cognition, verbal memory, and category fluency). Primary outcomes were the Telephone interview for Cognitive Status (TICS), global cognition (averaging all tests) and verbal memory (averaging four verbal tests). Multivariable linear regression models were used to estimate relations of insulin and c-peptide to cognitive decline.

Results

Higher fasting insulin was associated with worse decline on all tests, after adjustment. Findings were statistically significant for the TICS and category fluency: e.g., the multivariable-adjusted mean difference (95% CI) in decline for men with the highest vs. lowest insulin levels was −0.62 (−1.15, −0.09) points on the TICS (p-trend=0.04); this difference was similar to that between men 7 years apart in age. Similarly, there was worse decline across all tests with increasing c-peptide, but findings were statistically significant only for global score (p-trend=0.03).

Conclusions

Higher fasting insulin and greater insulin secretion in older men may be related to overall cognitive decline, even in the absence of diabetes.

Background

Higher adherence to the Mediterranean diet (MeDi) has been related to lower Alzheimer’s disease risk. Some dietary factors have been studied in patients with essential tremor (ET), but the MeDi’s effect has not been investigated.

Methods

Adherence to the MeDi was calculated from a food frequency questionnaire administered in a case-control study of environmental epidemiology of ET in the New York Tri-State area. Logistic regression models were used to examine whether adherence to the MeDi predicted ET (vs. control) outcome. The models adjusted for age, gender, ethnicity, education, caloric intake, body mass index, smoking, ethanol consumption, coffee intake and blood harmane concentrations.

Results

148 ET cases adhered less to MeDi (0–9 scale with higher scores indicating higher adherence) than 250 controls (mean 4.3 ± 1.7 vs. 4.7 ± 1.7; p = 0.03). Higher adherence to MeDi was associated with lower odds for ET [0.78 (0.61–0.99); p = 0.042]. As compared to subjects at the lowest MeDi adherence tertile, those at the middle tertile had lower ET odds [0.41 (0.16–1.05)], while subjects at the highest tertile had an even lower ET odds [0.29 (0.10–0.82); p for trend 0.021].

Conclusions

Compared to controls, ET cases adhered less to MeDi. The gradual reduction in ET odds with higher MeDi adherence tertiles suggests a possible dose-response effect. The mechanisms that underlie this association merit further study.

Essential tremor (ET) has traditionally been viewed as monosymptomatic. However, there is an emerging appreciation of an expanded number of motor manifestations as well as a new awareness of nonmotor manifestations. The current goal, through factor analyses, was to determine how these diverse signs relate to one another and shed light on their pathogenic bases. One hundred and thirty-eight ET patients had detailed neurological examinations. In these analyses, three separate factors emerged, explaining 58.7% of the variance. Factor I was comprised of the hallmark feature of ET, action tremor. It also included intention tremor, which is generally viewed as a sign of cerebellar dysfunction, and tremor duration. Factor II was comprised of cognitive test scores and age, and factor III, of rest tremor. Cognitive test scores did not fall into the same domain as motor features or tremor duration. These results suggest that: (1) the process that underlies cognitive dysfunction in ET is distinct from that which is responsible for action and intention tremors and their progression over time, and (2) cognitive dysfunction in ET is not likely due to cerebellar degeneration. Age loaded with cognitive test scores, further raising the possibility that age-related processes (e.g. Alzheimer-type changes) could underlie cognitive changes in ET.

Background

The effects of oophorectomy on brain aging remain uncertain.

Methods

We conducted a cohort study with long-term follow-up of women in Olmsted County, Minn., USA, who underwent either unilateral or bilateral oophorectomy before the onset of menopause from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone any oophorectomy. We studied underlying and contributory causes of death in 1,274 women with unilateral oophorectomy, 1,091 women with bilateral oophorectomy, and 2,383 referent women.

Results

Mortality for neurological or mental diseases was increased in women who underwent bilateral oophorectomy before age 45 years compared with referent women (hazard ratio = 5.24; 95% confidence interval = 2.02–13.6; p < 0.001). Within this age stratum, mortality was similar in women who were or were not treated with estrogen from the time of oophorectomy through age 45 years, and in women who had bilateral oophorectomy for prophylaxis or for treatment of a benign ovarian condition. Mortality was also increased in women who underwent unilateral oophorectomy before age 45 years without concurrent hysterectomy.

Conclusions

Bilateral oophorectomy performed before age 45 years is associated with increased mortality for neurological or mental diseases.

Background

Our aims were to: (1) estimate the prevalence of essential tremor (ET) in a community-based study in northern Manhattan, New York, N.Y., USA; (2) compare prevalence across ethnic groups, and (3) provide prevalence estimates for the oldest old.

Methods

This study did not rely on a screening questionnaire. Rather, as part of an in-person neurological evaluation, each participant produced several handwriting samples, from which ET diagnoses were assigned.

Results

There were 1,965 participants (76.7 ± 6.9 years, range = 66–102 years); 108 had ET [5.5%, 95% confidence interval (CI) = 4.5–6.5%]. Odds of ET were robustly associated with Hispanic ethnicity versus white ethnicity [odds ratio (OR) = 2.19, 95% CI = 1.03–4.64, p = 0.04] and age (OR = 1.14, 95% CI = 1.03–1.26, p = 0.01), i.e. with every 1 year advance in age, the odds of ET increased by 14%. Prevalence reached 21.7% among the oldest old (age ≥95 years).

Conclusions

This study reports a significant ethnic difference in the prevalence of ET. The prevalence of ET was high overall (5.5%) and rose markedly with age so that in the oldest old, more than 1 in 5 individuals had this disease.

Background

The interpretation of neuropathological studies of dementia and Alzheimer's disease is complicated by potential selection mechanisms that can drive whether or not a study participant is observed to undergo autopsy. Notwithstanding this, there appears to have been little emphasis placed on potential selection bias in published reports from population-based neuropathological studies of dementia.

Methods

We provide an overview of methodological issues relating to the identification of and adjustment for selection bias. When information is available on factors that govern selection, inverse-probability weighting provides an analytic approach to adjust for selection bias. The weights help alleviate bias by serving to bridge differences between the population from which the observed data may be viewed as a representative sample and the target population, identified as being of scientific interest.

Results

We illustrate the methods with data obtained from the Adult Changes in Thought study. Adjustment for potential selection bias yields substantially strengthened association between neuropathological measurements and risk of dementia.

Conclusions

Armed with analytic techniques to adjust for selection bias and to ensure generalizability of results from population-based neuropathological studies, researchers should consider incorporating information related to selection into their data collection schemes.

Background

The interpretation of neuropathological studies of dementia and Alzheimer’s disease is complicated by potential selection mechanisms that can drive whether or not a study participant is observed to undergo autopsy. Notwithstanding this, there appears to have been little emphasis placed on potential selection bias in published reports from population-based neuropathological studies of dementia.

Methods

We provide an overview of methodological issues relating to the identification of and adjustment for selection bias. When information is available on factors that govern selection, inverse-probability weighting provides an analytic approach to adjust for selection bias. The weights help alleviate bias by serving to bridge differences between the population from which the observed data may be viewed as a representative sample and the target population, identified as being of scientific interest.

Results

We illustrate the methods with data obtained from the Adult Changes in Thought study. Adjustment for potential selection bias yields substantially strengthened association between neuropathological measurements and risk of dementia.

Conclusions

Armed with analytic techniques to adjust for selection bias and to ensure generalizability of results from population-based neuropathological studies, researchers should consider incorporating information related to selection into their data collection schemes.

Background

The effects of oophorectomy on brain aging remain uncertain.

Methods

We conducted a cohort study with long-term follow-up of women in Olmsted County, MN, who underwent either unilateral or bilateral oophorectomy before the onset of menopause from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone any oophorectomy. We studied underlying and contributory causes of death in 1,274 women with unilateral oophorectomy, 1,091 women with bilateral oophorectomy, and 2,383 referent women.

Results

Mortality for neurological or mental diseases was increased in women who underwent bilateral oophorectomy before age 45 years compared with referent women (hazard ratio [HR] = 5.24; 95% confidence interval [CI] = 2.02–13.6; p <0.001). Within this age stratum, mortality was similar in women who were or were not treated with estrogen from the time of oophorectomy through age 45 years and in women who had bilateral oophorectomy for prophylaxis or to treat a benign ovarian condition. Mortality was also increased in women who underwent unilateral oophorectomy before age 45 years without concurrent hysterectomy.

Conclusions

Bilateral oophorectomy performed before age 45 years is associated with increased mortality for neurological or mental diseases.

Background/Aims

Little is known about the possible effects of social resources on stroke survivors' level and change in cognitive outcomes. Understanding this association may help us identify strategies to improve stroke recovery and help elucidate the etiology of dementia.

Methods

We examined the relationship of social ties and social support to cognitive function and cognitive change 6 months after stroke. Participants in the Families in Recovery from Stroke Trial (FIRST) (n = 272) were interviewed approximately 17 days (baseline) and 6 months (follow-up) after stroke. Cognition was assessed with the Mini Mental State Examination (MMSE) and a summary battery of 7 neuropsychological tests. Median-based regression was used to model cognitive outcomes by level of baseline intimate, personal and organizational social ties and received emotional and instrumental support.

Results

Baseline social ties and emotional support independently predicted 6-month Cognitive Summary Scores. Emotional support also predicted greater improvements in Cognitive Summary Scores from baseline to the 6-month follow-up. No other social exposures predicted improvements in the MMSE or the Cognitive Summary.

Conclusions

Our results suggest that emotional support may promote cognitive resilience while social ties provide cognitive reserve that protects against impaired cognition after stroke. Social ties did not predict cognitive recovery however, so reverse causation cannot be ruled out.

Background

Although comorbid neurological conditions are not uncommon for individuals undergoing lower-extremity amputation (LE), short- and long-term prognosis is unclear.

Methods

This cohort study on the survival of United States veterans with LE amputations examined the association between different preexisting neurological conditions and short- and long-term (in-hospital and within 1-year of surgical amputation) mortality. X2and t test statistics compared baseline characteristics for patients with and without neurological disorders. Multiple logistic regression and Cox proportional hazard models were used to examine short- and long-term survival and identify predictors limited to the subset of those with neurological conditions adjusting for age, amputation level, etiology, and comorbidities.

Results

Of 4,720 patients, 43.3% had neurological disorders documented. Most prevalent were stroke or hemiparesis (18.3%) and peripheral nervous system (PNS) disorders (20.3%). Among patients with neurological conditions, those with a PNS disorder or spinal cord injury (or paralysis) were significantly less likely to die in hospital and within 1 year (p<0.05) when compared to the other types of neurological condition groups including stroke (or hemiparesis), cerebral degenerative diseases, movement disorders and autonomic disorders.

Conclusions

The high prevalence of preexisting neurological disorders among LE amputees and the varying effect of different conditions on risk of mortality highlights the need to further characterize the diverseness of this understudied subpopulation. While preexisting spinal cord injury and PNS disorders appear to carry decreased risk among amputees, those with central nervous system disorders have comparatively greater mortalities.

Background

Although comorbid neurological conditions are not uncommon for individuals undergoing lower-extremity (LE) amputation, short- and long-term prognosis is unclear.

Methods

This cohort study on the survival of United States veterans with LE amputations examined the association between different preexisting neurological conditions and short- and long-term (in-hospital and within 1-year of surgical amputation) mortality. χ2 and t test statistics compared baseline characteristics for patients with and without neurological disorders. Multiple logistic regression and Cox proportional hazard models were used to examine short- and long-term survival and identify predictors limited to the subset of those with neurological conditions adjusting for age, amputation level and etiology, and co-morbidities.

Results

Of 4,720 patients, 43.3% had neurological disorders documented. Most prevalent were stroke or hemiparesis (18.3%) and peripheral nervous system (PNS) disorders (20.3%). Among patients with neurological conditions, those with a PNS disorder or spinal cord injury (or paralysis) were significantly less likely to die in hospital and within 1 year (p < 0.05) when compared to the other types of neurological condition groups including stroke (or hemiparesis), cerebral degenerative diseases, movement disorders and autonomic disorders.

Conclusions

The high prevalence of preexisting neurological disorders among LE amputees and the varying effect of different conditions on risk of mortality highlights the need to further characterize the diverseness of this understudied subpopulation. While preexisting spinal cord injury and PNS disorders appear to carry a decreased risk among amputees, those with central nervous system disorders have comparatively greater mortalities.

Background

The National Institutes of Health Stroke Scale (NIHSS) provides a standardized measure of stroke severity and is frequently captured to assess 3-month outcome. Other outcome measures have been assessed for the relationship to dependence; a clinically relevant outcome. The relationship between NIHSS score and functional dependence is unknown. The purpose of this study was to assess the relationship between NIHSS score and accepted measures of dependence in surviving ischemic stroke patients.

Methods

3-month NIHSS scores were compared to residence and Glasgow Outcome Scale (GOS) scores at 3 months in the Randomized Trial of Tirilazad Mesylate in Patients with Acute Stroke (RANTTAS). For residence, patients who were in a nursing home, chronic hospital or substantially dependent on a caregiver were characterized as ‘dependent’. For GOS, a score of 3 (severely disabled) or 4 (vegetative) was characterized as ‘dependent’. The sensitivity, specificity and positive (PPV) and negative predictive values (NPV) for various NIHSS score cut points compared to dependence were calculated. Logistic regression analysis was used to assess the association between the NIHSS score and dependence.

Results

In 385 subjects from the RANTTAS, an NIHSS score cut point of ≥ 15 resulted in 100% of subjects identified as being dependent by residence, sensitivity = 24%, specificity = 100%, PPV = 100% and NPV = 80%. Using GOS as the measure of dependence, the results were almost identical. NIHSS was strongly related to dependence with an area under the receiver operating characteristic curve (AUC) = 0.86 for residence and an AUC = 0.94 for GOS.

Conclusions

3-month NIHSS score is strongly associated with dependence. An NIHSS score of ≥ 15 at 3 months may be a reasonable estimate of subjects who are highly likely to be dependent at 3 months. These data require validation in an independent data set.

Background

Our aims were to: (1) estimate the prevalence of essential tremor (ET) in a community-based study in northern Manhattan, New York, (2) compare prevalence across ethnic groups, and (3) provide prevalence estimates for the oldest old.

Methods

This study did not rely on a screening questionnaire. Rather, as part of an in-person neurological evaluation, each participant produced several handwriting samples, from which ET diagnoses were assigned.

Results

There were 1,965 participants (76.7 ± 6.9 years, range = 66 – 102 years); 108 had ET (5.5%, 95% confidence interval [CI] = 4.5%–6.5%). Odds of ET were robustly associated with Hispanic ethnicity vs. White ethnicity (odds ratio [OR] = 2.19, 95% CI = 1.03–4.64, p = 0.04) and age (OR = 1.14, 95% CI = 1.03–1.26, p = 0.01)(i.e., with every 1 year advance in age, the odds of ET increased by 14%). Prevalence reached 21.7% among the oldest old (age ≥95 years).

Conclusions

This study reports a significant ethnic difference in the prevalence of ET. The prevalence of ET was high overall (5.5%) and rose markedly with age so that in the oldest old, more than one of five individuals had this disease.

Objectives

To test the hypothesis that respiratory muscle strength is associated with the rate of change in mobility even after controlling for leg strength and physical activity.

Methods

Prospective study of 890 ambulatory older persons without dementia who underwent annual clinical evaluations to examine change in the rate of mobility over time.

Results

In a linear mixed-effects model adjusted for age, sex, and education, mobility declined about 0.12 unit/year, and higher levels of respiratory muscle strength were associated with a slower rate of mobility decline (Estimate, 0.043; S.E., 0.012, p<0.001). Respiratory muscle strength remained associated with the rate of change in mobility even after controlling for lower extremity strength (Estimate, 0.036; S.E., 0.012, p=0.004). In a model that included terms for respiratory muscle strength, lower extremity strength and physical activity together, all three were independent predictors of mobility decline in older persons. These associations remained significant even after controlling for body composition, global cognition, the development of dementia, parkinsonian signs, possible pulmonary disease, smoking, joint pain and chronic diseases.

Conclusion

Respiratory muscle strength is associated with mobility decline in older persons independent of lower extremity strength and physical activity. Clinical interventions to improve respiratory muscle strength may decrease the burden of mobility impairment in the elderly.

Background

While decreased hemoglobin concentration is common in the elderly, the relationship of the entire range of hemoglobin concentrations with cognitive function is not well understood.

Methods

Cross-sectional analyses were conducted utilizing data from community-dwelling, older persons participating in the Rush Memory and Aging Project. Proximate to first available hemoglobin measurement, twenty-one cognitive tests were administered to measure global cognitive function along with semantic memory, episodic memory, working memory, perceptual speed, and visuospatial abilities.

Results

For 793 participants without clinical dementia, stroke or Parkinson's disease, mean age was 81.0 years (SD=7.2), 595 (75%) were women, and 94% were white. Mean hemoglobin concentration was 13.3 g/dL (SD=1.3). 17% of the cohort had anemia. Using linear regression models adjusted for age, education, gender, body mass index, mean corpuscular volume, and glomerular filtration rate, both low and high hemoglobin levels were associated with lower global cognitive function (parameter estimate=-0.015, SE=0.007, p=0.019). Low and high hemoglobins were associated with worse performance on semantic memory (parameter estimate=-0.201, SE=0.008, p=0.010) and perceptual speed (parameter estimate=-0.030, SE=0.010, p=0.004), but not the other specific cognitive functions.

Conclusions

Low and high hemoglobin concentrations in older persons are associated with lower level of cognitive function in old age, particularly in semantic memory and perceptual speed.

Background

Mexican Americans (MAs) have increased risk of stroke compared with non-Hispanic whites (NHWs), especially at younger ages. Little is known regarding patterns of familial aggregation of stroke and whether familial risk assessment might prove a potentially useful tool in assessing stroke risk in this population. This study's objective was to estimate the sibling recurrence risk ratio (λs) for stroke and to compare this ratio between MAs and NHWs.

Methods

Stroke and transient ischemic attack (TIA) cases (n=181) between ages 45–64 were identified through a population-based stroke study in a bi-ethnic Texas community. λs was calculated overall and by ethnicity.

Results

Siblings of ischemic stroke/TIA cases had a doubling in stroke risk compared to what would be expected based on national stroke prevalence estimates (λs=1.92; 95% CI:1.39–2.61). λs was 2.0 (95% CI:1.39–2.81) among MA stroke/TIA cases and 1.66 (95% CI:0.82–3.10) among NHW stroke/TIA cases.

Conclusion

Sibling recurrence risk for stroke was elevated in MA stroke/TIA cases suggesting that further ischemic stroke genetic studies across ethnicities may be warranted. In addition, a positive family history could prove a useful factor in the clinical setting for identifying MAs at increased stroke risk.

Aim

To estimate the prevalence of Alzheimer’s disease (AD) and other dementias in the USA using a nationally representative sample.

Methods

The Aging, Demographics, and Memory Study sample was composed of 856 individuals aged 71 years and older from the nationally representative Health and Retirement Study (HRS) who were evaluated for dementia using a comprehensive in-home assessment. An expert consensus panel used this information to assign a diagnosis of normal cognition, cognitive impairment but not demented, or dementia (and dementia subtype). Using sampling weights derived from the HRS, we estimated the national prevalence of dementia, AD and vascular dementia by age and gender.

Results

The prevalence of dementia among individuals aged 71 and older was 13.9%, comprising about 3.4 million individuals in the USA in 2002. The corresponding values for AD were 9.7% and 2.4 million individuals. Dementia prevalence increased with age, from 5.0% of those aged 71–79 years to 37.4% of those aged 90 and older.

Conclusions

Dementia prevalence estimates from this first nationally representative population-based study of dementia in the USA to include subjects from all regions of the country can provide essential information for effective planning for the impending healthcare needs of the large and increasing number of individuals at risk for dementia as our population ages.

Essential tremor (ET) has traditionally been viewed as monosymptomatic. However, there is an emerging appreciation of an expanded number of motor manifestations as well as new awareness of non-motor manifestations. The current goal, through factor analyses, was to determine how these diverse signs relate to one another and shed light on their pathogenic bases. One-hundred-thirty-eight ET patients had detailed neurological examinations. In these analyses, three separate factors emerged, explaining 58.7% of the variance. Factor I was comprised of the hallmark feature of ET, action tremor. It also included intention tremor, which is generally viewed as a sign of cerebellar dysfunction, and tremor duration. Factor II was comprised of cognitive test scores and age, and Factor III, of rest tremor. Cognitive test scores did not fall into the same domain as motor features or tremor duration. These results suggest that: (1) the process that underlies cognitive dysfunction in ET is distinct from that which is responsible for action and intention tremors and their progression over time, and (2) cognitive dysfunction in ET is not likely due to cerebellar degeneration. Age loaded with cognitive test scores, further raising the possibility that age-related processes (e.g., Alzheimer-type changes) could underlie cognitive changes in ET.

Background

Essential tremor (ET) is one of the most common neurological disorders. Despite this, the disease mechanisms and etiology are not well understood. While susceptibility genotypes undoubtedly underlie many ET cases, no ET genes have been identified thus far. As with many other progressive, degenerative neurological disorders, it is likely that environmental factors contribute to the etiology of ET. Environmental epidemiology is the study in specific populations or communities of the effect on human health of physical, biologic, and chemical factors in the external environment. The purpose of this article is to review current knowledge with regards to the environmental epidemiology of ET.

Methods

Review.

Results

As will be discussed, a series of preliminary case-control studies in recent years have begun to explore several candidate toxins/exposures, including harmane (1-methyl-9H-pyrido[3,4-b]indole), lead, and agricultural exposures/pesticides.

Conclusions

While several initial results are promising, as will be discussed, additional studies are needed to more definitively establish whether these exposures are associated with ET and are of etiological importance.

Background

A view of essential tremor (ET) as a degenerative disorder, now gaining support from postmortem studies, is at odds with traditional views of ET as a “super-healthy” condition characterized by increased longevity and fertility. Longevity has recently been re-examined in ET, yet fertility, measured by number of offspring, has never been critically assessed in this disease.

Objective

To determine whether ET cases and controls differ in terms of number of children.

Methods

Family history data were collected on ET cases and controls from two distinct sources, a population and a clinical (referred) sample.

Results

In the population, number of children was similar in 59 cases vs. 72 controls (mean ± SD [median] = 2.3 ± 2.9 [1] vs. 2.2 ± 1.8 [2], p = 0.26). In the referred sample, number of children was similar in 184 cases vs. 241 controls (2.0 ± 1.5 [2] vs. 1.9 ± 1.7 [2], p = 0.33). In adjusted analyses, results were similar.

Conclusions

Fertility, measured by number of children, was similar in cases and controls. With a newer understanding of the biological substrate of ET emerging from postmortem studies, it is important to critically re-assess this and other fundamental biological questions about the disease.

Recent reports of a potentially increased risk of amyotrophic lateral sclerosis (ALS) for veterans deployed to the 1990-91 Persian Gulf War prompted the Department of Veterans Affairs to establish a National Registry of Veterans with ALS, charged with the goal of enrolling all US veterans with a neurologist-confirmed diagnosis of ALS (Allen et al., this issue). The GENEVA study (Genes and Environmental Exposures in Veterans with ALS) is a case-control study presently enrolling cases from the VA registry and a representative sample of veteran controls to evaluate the joint contributions of genetic susceptibility and environmental exposures to the risk of sporadic ALS. The GENEVA study design, recruitment strategies, and methods of collecting DNA samples and environmental risk factor information are described here, along with a summary of demographic characteristics of the participants (537 cases, 292 controls) enrolled to date.

To plan a multisite, ischemic stroke genetic study, stroke patients were surveyed about the availability and characteristics of a convenience sample of spouse/friend controls. 65% of all stroke-affected probands reported a living spouse. A more detailed survey was conducted at the University of Virginia, Charlottesville, Va., USA: 51% of stroke patients reported a living, stroke-free spouse who would be willing to serve as a control, and 49% reported having a stroke-free friend who would be willing to serve as a control. Overall, 75% of stroke patients reported at least 1 individual willing to participate as a control. Cases without an identified control were more likely to be non-white (48%) than were cases with a control (13%; p = 0.00004). Cases were older than controls (67.3 vs. 59.2 years; p = 0.000002), and a greater proportion of cases than controls were male (57 vs. 33%; p = 0.0002). Without proper attention to matching, the use of a spouse/friend convenience sample would result in imbalances in basic demographic characteristics.