Biomedical subjects

L J Launer

Publications and source records attributed to L J Launer.

At least 19 recordsLinked to original sources

PubMed2006

Syncope in migraine: the population-based CAMERA study.

OBJECTIVE: To examine the association between migraine and syncope-related autonomic nervous system (ANS) symptoms. METHODS: A population-based study among migraineurs with and without aura (n = 323) and control subjects (n = 153) was conducted. A systematic questionnaire and cardiovascular measurements during rest, while standing, and after venipuncture addressed the prevalence of syncope, orthostatic intolerance, orthostatic hypotension (OH), and the postural tachycardia syndrome (POTS) in migraineurs and control subjects. RESULTS: The lifetime prevalence of syncope in all participants was 41%, more often in women (45 vs 32%; p = 0.02). Compared with control subjects, migraineurs had a higher lifetime prevalence of syncope (46 vs 31%; p = 0.001), frequent syncope (five or more attacks) (13 vs 5%; p = 0.02), and orthostatic intolerance (32 vs 12%; p < 0.001). There was no association between ANS symptoms and the severity of migraine or migraine subtype. Cardiovascular measurements and the prevalence of POTS and OH did not differ significantly between migraineurs and control subjects. CONCLUSION: This population-based study demonstrated an elevated prevalence of syncope and orthostatic intolerance in migraineurs without clear interictal signs of autonomic nervous system dysfunction.

Blood Pressure↗

PubMed2006

Analysis and validation of automated skull stripping tools: a validation study based on 296 MR images from the Honolulu Asia aging study.

As population-based epidemiologic studies may acquire images from thousands of subjects, automated image post-processing is needed. However, error in these methods may be biased and related to subject characteristics relevant to the research question. Here, we compare two automated methods of brain extraction against manually segmented images and evaluate whether method accuracy is associated with subject demographic and health characteristics. MRI data (n = 296) are from the Honolulu Asia Aging Study, a population-based study of elderly Japanese-American men. The intracranial space was manually outlined on the axial proton density sequence by a single operator. The brain was extracted automatically using BET (Brain Extraction Tool) and BSE (Brain Surface Extractor) on axial proton density images. Total intracranial volume was calculated for the manually segmented images (ticvM), the BET segmented images (ticvBET) and the BSE segmented images (ticvBSE). Mean ticvBSE was closer to that of ticvM, but ticvBET was more highly correlated with ticvM than ticvBSE. BSE had significant over (positive error) and underestimated (negative error) ticv, but net error was relatively low. BET had large positive and very low negative error. Method accuracy, measured in percent positive and negative error, varied slightly with age, head circumference, presence of the apolipoprotein eepsilon4 polymorphism, subcortical and cortical infracts and enlarged ventricles. This epidemiologic approach to the assessment of potential bias in image post-processing tasks shows both skull-stripping programs performed well in this large image dataset when compared to manually segmented images. Although method accuracy was statistically associated with some subject characteristics, the extent of the misclassification (in terms of percent of brain volume) was small.

Aged↗

PubMed2006

Inflammation and dementia: epidemiologic evidence.

Based on experimental and neuropathologic studies, inflammation is postulated to play a central role in processes leading to neurodegeneration as well as vascular injury. To better understand the role of inflammation in cognitive disorders (CD), identify potential biomarkers for CD, and select individuals who may have a genetic susceptibility to CD, several different measures of inflammation have been employed in epidemiologic studies of CD, which are reviewed here. An inverse association of non-steroidal anti-inflammatory medications has been consistently reported. More variable are reports on the associations of various serum markers of cytokines to CD. There are few epidemiologic studies that have examined the association of CD and single nucleotide polymorphisms (SNP) regulating cytokines, although these have been examined in clinical case-control series. Data are summarized on the association of interleukin-1 SNPs from the Honolulu Asia Aging Study. There are many outstanding questions about the role of inflammation in CD and how best to measure it in the context of population-based studies.

Acute-Phase Proteins↗

PubMed2006

Intracranial compartment volumes in normal pressure hydrocephalus: volumetric assessment versus outcome.

BACKGROUND AND PURPOSE: Although enlargement of the cerebral ventricles plays a central role in the diagnosis of normal pressure hydrocephalus (NPH), there are no reports on the use of volumetric assessment to distinguish between patients who respond to ventriculoperitoneal shunt surgery and those who do not. The purpose of this study is to explore the association between preoperative intracranial compartment volumes and postoperative improvement. METHODS: Twenty-six patients (17 men; mean age, 75 years [range, 54-87 years]) with a clinical or radiologic suspicion of NPH were included in the study. Gait, cognition, and bladder function were evaluated by clinical rating. MR imaging of the brain was acquired at 0.5 T and 1.5 T. Total intracranial volume, ventricular volume, brain volume, and pericerebral CSF volume were determined by volumetric assessment. Four imaging variables were determined: ventricular volume ratio, brain volume ratio, pericerebral CSF volume ratio, and the ratio of ventricular volume to pericerebral CSF volume. All patients underwent ventriculoperitoneal shunt surgery. RESULTS: Clinical follow-up was assessed 1 year after shunt surgery. No difference in the mean ventricular volume ratio, the mean brain volume ratio, the mean pericerebral CSF volume ratio, and the mean ratio between ventricular and pericerebral CSF volume was found between subjects who improved on gait or cognition or bladder function and those who did not. CONCLUSION: Volumetric assessment has no predictive value in differentiating between NPH patients who respond to ventriculoperitoneal shunt surgery and those who do not.

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PubMed2005

Regional variability in the prevalence of cerebral white matter lesions: an MRI study in 9 European countries (CASCADE).

White matter lesions (WML) on MRI of the brain are common in both demented and nondemented older persons. They may be due to ischemic events and are associated with cognitive and physical impairments. It is not known whether the prevalence of these WML in the general population differs across European countries in a pattern similar to that seen for coronary heart disease. Here we report the prevalence of WML in 1,805 men and women drawn from population-based samples of 65- to 75-year-olds in ten European cohorts. Data were collected using standardized methods as a part of the multicenter study CASCADE (Cardiovascular Determinants of Dementia). Centers were grouped by region: south (Italy, Spain, France), north (Netherlands, UK, Sweden), and central (Austria, Germany, Poland). In this 10-year age stratum, 92% of the sample had some lesions, and the prevalence increased with age. The prevalence of WML was highest in the southern region, even after adjusting for differences in demographic and selected cardiovascular risk factors. Brain aging leading to disabilities will increase in the future. As a means of hypothesis generation and for health planning, further research on the geographic distribution of WML may lead to the identification of new risk factors for these lesions.

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PubMed2005

Brain lesions on MRI and endogenous sex hormones in elderly men.

We investigated the association between MRI detected brain lesions and levels of endogenous sex hormones in Japanese-American men aged 74-95 years. Logistic regression was used to estimate the association (OR (95% CI)) of MRI outcome with tertiles of bioavailable testosterone, 17beta estradiol and sex hormone binding globulin (SHBG). There was a significantly increased risk for cerebral atrophy in the highest tertile of testosterone (3.1 (1.2-7.8)) compared to the lowest. We also found that men with the highest estradiol had a higher risk of lacunes (1.92 (1.1-3.2)). These relationships did not change with adjustment for the other sex hormones, cardiovascular risk factors, or other brain lesions. In contrast, men with the highest SHBG had a lower risk both of cerebral atrophy and lacunes, after adjusting for sex hormones and cardiovascular risk factors. There were no associations between sex hormones and hippocampal atrophy, white matter lesions, and large infarcts. Because the levels of hormone were measured close in time to the acquisition of the MRI, these associations may reflect neurodegeneration in brain regions regulating hormone levels.

Aged↗

PubMed2005

Cardiovascular risk factors and migraine: the GEM population-based study.

BACKGROUND: Migraine, particularly with aura, is a risk factor for early-onset ischemic stroke. The underlying mechanisms are unknown, but may in part be due to migraineurs having an increased risk profile for cardiovascular disease. In this study, the authors compare the cardiovascular risk profile of adult migraineurs to that of nonmigraineurs. METHODS: Participants (n = 5,755, 48% men, age 20 to 65 years) are from the Genetic Epidemiology of Migraine (GEM) study, a population-based study in the Netherlands. A total of 620 current migraineurs were identified: 31% with aura (MA), 64% without aura (MO), and 5% unclassified. Controls were 5,135 individuals without lifetime migraine. Measured cardiovascular risk factors included blood pressure (BP), serum total and high-density lipoprotein cholesterol (TC, HDL), smoking, oral contraceptive use, and the Framingham risk score for myocardial infarction or coronary heart disease (CHD) death. RESULTS: Compared to controls, migraineurs were more likely to smoke (OR = 1.43 [1.1 to 1.8]), less likely to consume alcohol (OR = 0.58 [0.5 to 0.7]), and more likely to report a parental history of early myocardial infarction. Migraineurs with aura were more likely to have an unfavorable cholesterol profile (TC > or = 240 mg/dL [OR = 1.43 (0.97 to 2.1)], TC:HDL ratio > 5.0 [OR = 1.64 (1.1 to 2.4)]), have elevated BP (systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg [OR = 1.76 (1.04 to 3.0)]), and report a history of early onset CHD or stroke (OR = 3.96 [1.1 to 14.3]); female migraineurs with aura were more likely to be using oral contraceptives (OR = 2.06 [1.05 to 4.0]). The odds of having an elevated Framingham risk score for CHD were approximately doubled for the migraineurs with aura. CONCLUSIONS: Migraineurs, particularly with aura, have a higher cardiovascular risk profile than individuals without migraine.

Adult↗

PubMed2005

Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe.

BACKGROUND: Blood pressure level is associated with the risk of clinical Alzheimer disease (AD), yet the underlying mechanisms are unclear. High blood pressure levels may cause cerebral small-vessel pathology, which contributes to cognitive decline in patients with AD. Alternatively, in persons with high blood pressure, increased numbers of neurofibrillary tangles and amyloid plaques at autopsy have also been observed, suggesting direct links between blood pressure and AD. OBJECTIVE: To investigate the association of blood pressure and markers of small-vessel disease (white matter lesions [WMLs] on MRI) with hippocampal and amygdalar atrophy on MRI-potential in vivo indicators of Alzheimer pathology. METHODS: In 1995 to 1996, 511 nondemented elderly subjects (age 60 to 90) underwent MRI. The extent of WMLs was assessed, and volumes of the hippocampus and amygdala were measured. Blood pressure levels were assessed at the time of MRI and 5 years before the MRI. RESULTS: Higher diastolic blood pressure 5 years before MRI predicted more hippocampal atrophy in persons untreated for hypertension (per SD increase -0.10 mL [95% CI -0.19 to -0.02, p = 0.02]). Conversely, in persons treated for hypertension, a low diastolic blood pressure was associated with more severe atrophy. Persons with more WMLs on MRI more often had severe atrophy of the hippocampus and amygdala. CONCLUSION: Blood pressure and indicators of small-vessel disease in the brain may be associated with atrophy of structures affected by Alzheimer pathology.

Adult↗

PubMed2005

The epidemiologic study of dementia: a life-long quest?

Based on many experimental and observational studies we now understand that neurodegenerative brain changes begin by middle age. Characteristics of the risk factors for these brain changes may also change with age. A review is conducted of studies that report on the association of mid-life risk factors to late cognitive impairment and dementia. Issues related to the interpretation of the data are discussed. The studies suggest that mid-life cardiovascular risk factors, and in particular elevated levels of blood pressure, increase the risk for late-life cognitive impairment and dementia. Our understanding the contribution of cardiovascular risk factors to late age brain disease has been helped tremendously by prospective studies with long follow-up. To better understand which risk factors lead to disease initiation, progression and prognosis, a life course approach to the epidemiologic study of dementia is needed.

Aged↗

PubMed2005

MRI findings in migraine.

INTRODUCTION: For long time, migraine has been considered to be an episodic, multifactorial, neurovascular disorder, without long-term consequences to the brain, although an association between migraine and clinical stroke and white matter hyperintense lesions has been suggested in numerous studies. Due to various methodological problems no definite conclusion could be drawn from these studies. STATE OF THE ART: Recently, data from a population-based cross-sectional MRI study were published, establishing migraine to be a true and independent risk factor for white matter lesions (in female migraine patients) and subclinical posterior circulation territory infarcts. PERSPECTIVES: The methodology and results of previous investigations of a relationship between migraine and clinical ischemic stroke, silent infarction and white matter lesions are reviewed, and integrated in the results from the new population-based MRI study. CONCLUSION: Brain infarction occurs far more frequently than expected in migraine patients, most pronounced in migraine with aura (8 percent have subclinical cerebellar infarcts), although most infarcts remain clinically silent. Female migraine patients are at increased risk of deep white matter lesions, independent of the effects of cardiovascular risk factors. The influence of migraine severity (attack frequency) on the risk of both types of lesions suggests a causal relationship between migraine severity and lesion load. Future studies are needed to assess whether these (probably) ischemic lesions have relevant (long-term) functional correlates.

Brain↗

PubMed2004

Effect of smoking on global cognitive function in nondemented elderly.

BACKGROUND: Contrary to early case-control studies that suggested smoking protects against Alzheimer disease (AD), recent prospective studies have shown that elderly who smoke may be at increased risk for dementia. OBJECTIVE: To examine prospectively the effect of smoking on cognition in nondemented elderly. METHOD: In a multicenter cohort, the European Community Concerted Action Epidemiology of Dementia (EURODEM), including the Odense, Personnes Agées Quid (Paquid), Rotterdam, and Medical Research Council: Ageing in Liverpool Project-Health Aspects (MRC ALPHA) Studies, 17,610 persons aged 65 and over were screened and examined for dementia. After an average 2.3 years of follow-up, 11,003 nondemented participants were retested. Excluding incident dementia cases and those without baseline information on smoking gave an analytical sample of 9,209 persons. Average yearly decline in Mini-Mental State Examination (MMSE) score was compared among groups, adjusting for age, sex, baseline MMSE, education, type of residence, and history of myocardial infarction or stroke. RESULTS: MMSE score of persons who never smoked on average declined 0.03 point/year. The adjusted decline of former smokers was 0.03 point greater and of current smokers 0.13 point greater than never smokers (p < 0.001). Higher rates of decline by smoking were found in men and women, persons with and without family history of dementia, and in three of four participating studies. Higher cigarette pack-year exposure was correlated with a significantly higher rate of decline. CONCLUSION: Smoking may accelerate cognitive decline in nondemented elderly.

Age Distribution↗

PubMed2004

Population-based studies of AD: message and methods: an epidemiologic view.

Dementia is a growing public health problem because the numbers suffering the disease is increasing rapidly as the population ages. Over the past decade several longitudinal population-based studies were initiated and are still on-going. These studies will provide valuable insight into the risk factors for, and progression of dementia. However, there are several design and statistical challenges that are unique to studying dementia in the population and that need to be addressed. These challenges include aspects of both ascertainment of disease and definition of exposure. To reduce bias from prospective epidemiologic studies, not only are new approaches to definition of disease and exposure needed, but new epidemiologic or statistical methods may be required as well.

Alzheimer Disease↗

PubMed2004

Dietary intake of fatty acids and fish in relation to cognitive performance at middle age.

OBJECTIVE: To examine the associations of fatty acid and fish intake with cognitive function. METHODS: Data are from a cross-sectional population-based study among 1,613 subjects ranging from 45 to 70 years old. From 1995 until 2000, an extensive cognitive battery was administered and compound scores were constructed for memory, psychomotor speed, cognitive flexibility (i.e., higher order information processing), and overall cognition. A self-administered food-frequency questionnaire was used to assess habitual food consumption. The risk of impaired cognitive function (lowest 10% of the compound score) according to the energy adjusted intake of fatty acids was assessed with logistic regression, adjusting for age, sex, education, smoking, alcohol consumption, and energy intake. RESULTS: Marine omega-3 polyunsaturated fatty acids (PUFA) (eicosapentaenoic acid and docosahexaenoic acid) were inversely related to the risk of impaired overall cognitive function and speed (per SD increase: OR = 0.81, 95% CI 0.66 to 1.00 and OR = 0.72, 95% CI 0.57 to 0.90). Results for fatty fish consumption were similarly inverse. Higher dietary cholesterol intake was significantly associated with an increased risk of impaired memory and flexibility (per SD increase: OR = 1.27, 95% CI 1.02 to 1.57 and OR = 1.26, 95% CI 1.01 to 1.57). Per SD increase in saturated fat intake, the risk of impaired memory, speed, and flexibility was also increased, although not significantly. CONCLUSIONS: Fatty fish and marine omega-3 PUFA consumption was associated with a reduced risk and intake of cholesterol and saturated fat with an increased risk of impaired cognitive function in this middle-aged population.

Animals↗

PubMed2003

CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study.

OBJECTIVE: To investigate the relationship of amyloid neuropathology to postmortem CSF Abeta 42 levels in an autopsy sample of Japanese American men from the population-based Honolulu-Asia Aging Study. METHODS: In 1991, participants were assessed and diagnosed with dementia (including subtype) based on published criteria. At death CSF was obtained from the ventricles. Neuritic plaques (NP) and diffuse plaques in areas of the neocortex and hippocampus were examined using Bielschowsky silver stains. Cerebral amyloid angiopathy (CAA) was measured by immunostaining for beta4 amyloid in cerebral vessels in the neocortex. Neuropathologically confirmed AD was diagnosed using Consortium to Establish a Registry for Alzheimer's Disease criteria. In 155 autopsy samples, log transformed linear regression models were used to examine the association of NP and CAA to Abeta 42 levels, controlling for clinical dementia severity, time between diagnosis and death, age at death, brain weight, hours between death and collection of CSF, education, and APOE genotype. RESULTS: Higher numbers of NP in the neocortex (p trend = 0.001) and in the hippocampus (p trend = 0.03) were strongly associated with lower levels of Abeta 42. Individuals with CAA had lower Abeta 42 levels (beta coefficient = -0.48; 95% CI -0.9, -0.1). Compared to participants with a diagnosis of clinical dementia, those with pathologically confirmed AD had lower Abeta 42 levels (beta coefficient = -0.74; 95% CI -1.4, -0.1). CONCLUSION: The current study suggests that lower Abeta 42 levels reflect neuropathologic processes implicated in amyloid-related pathologies, such as NP and CAA.

Aged↗

PubMed2003

Quantification of regional glial fibrillary acidic protein levels in Alzheimer's disease.

OBJECTIVES: Our objectives were to quantify glial fibrillary acidic protein (GFAP) in brains of Alzheimer's disease (AD) cases, and non-AD controls to determine the regions with the most severe gliosis in AD. MATERIAL AND METHODS: In a case control design, we used an enzyme-linked immunosorbent assay (ELISA) to quantify GFAP in frozen brain from four areas of neocortex in 10 AD cases, 10 age-matched controls, and 10 younger controls from the Honolulu-Asia Aging Study autopsy archive. RESULTS: Median age at death was 83.5 years for cases and age-matched controls, and 77 years for younger controls. For the AD cases compared with the age-matched controls, levels of GFAP in occipital (P=0.01), parietal (P=0.028), and temporal lobes (P=0.004) (but not frontal) were significantly higher in the cases. The median GFAP excess in AD cases compared with age matched controls was highest in the temporal lobe. CONCLUSIONS: Regional quantification of GFAP reveals that the glial response is most prominent in the temporal lobe in AD.

Aged↗

PubMed2002

Hippocampal, amygdalar, and global brain atrophy in different apolipoprotein E genotypes.

The epsilon4 allele of the APOE gene increases the risk for AD, whereas the epsilon2 allele may be protective. The authors assessed the impact of APOE genotype on hippocampal, amygdalar, and global brain atrophy as putative markers of preclinical AD in a nondemented population. Carriers of epsilon4 had significantly more hippocampal and amygdalar atrophy than epsilon3epsilon3 subjects, but not more global brain atrophy. Carriers of epsilon2 did not have less brain atrophy than epsilon3epsilon3 subjects.

Aged↗

PubMed2002

Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study.

OBJECTIVE: To investigate the relationship between cerebral amyloid angiopathy (CAA), dementia, and cognitive function in an autopsy sample of 211 Japanese-American men from the population-based Honolulu-Asia Aging Study. METHODS: Starting in 1991, participants were assessed with the Cognitive Abilities Screening Instrument (CASI) and diagnosed with dementia (including subtype) based on published criteria. At autopsy, neuropathologists blinded to clinical data examined brains for neurofibrillary tangles (NFT), neuritic plaques (NP), and a number of vascular pathologies, including CAA. CAA was detected by immunostaining for betaA4 amyloid in parenchymal vessels in the neocortex and semiquantitatively rated. Linear regression models were used to examine the association of CASI score, dementia subtype, and CAA controlling for age at death, time between CASI administration and death, education, NP and NFT counts, infarcts, hemorrhage, and APOE genotype. RESULTS: A total of 44.1% of subjects had CAA in at least one neocortical area. The presence of CAA was associated with higher mean NFT and NP counts and having at least one APOE-epsilon4 allele. The interaction between CAA and AD on the adjusted mean CASI score was significant; compared with nondemented men without CAA, the CASI score was 16.6% lower in men with AD and no CAA and 45.9% lower in men with AD plus CAA. CONCLUSIONS: CAA may contribute to the clinical presentation of dementia by interacting with other neuronal pathologies, leading to more severe cognitive impairment in men with both CAA and AD compared with men with only AD or CAA.

Aged↗

PubMed2002

Serum thyroxine level and cognitive decline in euthyroid older women.

BACKGROUND: Clinical and subclinical hypothyroidism is associated with cognitive impairment. OBJECTIVE: This study investigated the association between thyroxine (T(4)) and thyroid-stimulating hormone (TSH) level and change over time in cognitive performance in a sample of older women with normal thyroid gland function. METHODS: T(4) and TSH were measured at baseline in 628 women (> or = 65 years) enrolled in the Women's Health and Aging Study, a community-based study of physically impaired women. Cognitive function was assessed at baseline and after 1, 2, and 3 years, using the Mini-Mental State Examination (MMSE). Incident cognitive decline was defined as a decrease of more than one point/year in MMSE score between baseline and the end of the follow-up. The analysis included 464 subjects with normal thyroid gland function with a baseline and at least one follow-up MMSE. RESULTS: At baseline there was no association between T(4) and TSH level and cognitive function. In longitudinal analysis, adjusting for age, race, level of education, and other covariates, compared with women in the highest T(4) tertile (8.1 to 12.5 microg/dL), those in the lowest tertile (4.5 to 6.5 microg/dL) had a greater decline in MMSE score (-0.25 point/year vs -0.12 point/year; p = 0.04). A total of 95 women (20.5%) had cognitive decline during the study period (mean MMSE decline, 5.5 points). Compared with women in the highest T(4) tertile, those in the lowest tertile had a twofold risk of cognitive decline (adjusted relative risk, 1.97; 95% CI, 1.10 to 3.50). The results were not modified by baseline cognitive and physical function. There was no association between baseline TSH level and change in cognitive function. CONCLUSIONS: In older women, low T(4) levels, within the normal range, were associated with a greater risk of cognitive decline over a 3-year period. Thyroid hormone levels may contribute to cognitive impairment in physically impaired women.

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