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Biomedical subjects

P A Wolf

Publications and source records attributed to P A Wolf.

At least 19 recordsLinked to original sources
PubMed2005

Association of sex steroid hormones with brain morphology and cognition in healthy elderly men.

BACKGROUND: There is inconsistent evidence of the presence and direction of the relationship between sex hormone concentrations and cognitive function in older men, and there is little published literature on the relationship of sex hormone concentrations and brain volume as measured by MRI. OBJECTIVE: To examine the hypothesis that midlife total serum concentrations of testosterone (T), estradiol, estrone, and sex hormone binding globulin (SHBG) predict cognitive task performance and regional brain volumes at 10- to 16-year follow-up, in a longitudinal sample of World War II veteran twin men. METHODS: Treating twins as individuals, linear regression models were used, adjusting analyses for age, education, depressive symptomatology, blood pressure, alcohol consumption, years of cigarette smoking, and APOE epsilon4 allele status. RESULTS: There were no significant associations between sex hormone or SHBG concentrations and performance on a series of cognitive tasks measuring global and executive function, visual and verbal learning and memory. Higher midlife T concentrations were associated with larger hemispheric, frontal, and parietal regional brain volumes and with smaller left occipital brain volume. Higher estradiol and estrone concentrations were also associated with smaller right (estradiol) and both right and left (estrone) occipital volumes, but with no other brain regions. Owing to the multiple comparisons conducted, some significant associations may have occurred by chance. CONCLUSIONS: Overall, the pattern of results suggests a role for sex hormones in brain volume that predates potentially observable associations between sex hormones and cognitive task performance.

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PubMed2004

Stroke risk profile, brain volume, and cognitive function: the Framingham Offspring Study.

BACKGROUND: Mid-life stroke risk factors have been related to late-life cognitive impairment. This association may result not only from clinical strokes but also from subclinical brain injury, such as a global atrophy demonstrable on quantitative brain MRI. METHODS: The authors evaluated the community-based cohort of Framingham Offspring Study participants. A total of 1,841 subjects (mean age, 62 years; 857 men, 984 women) who underwent quantitative MRI and cognitive testing between 1999 and 2001 and were free of clinical stroke and dementia constituted our study sample. The authors used age- and sex-adjusted linear regression models to relate previous (1991 to 1995) and recent (1998 to 2001) Framingham Stroke Risk Profile (FSRP) scores to the total cerebral brain volume ratio (TCBVr) on follow-up MRI, and further to relate the TCBVr with education-adjusted scores on neuropsychological tests administered at the time of imaging. RESULTS: There was an inverse association between FSRP scores and TCBVr. The TCBVr also showed a significant positive association with performance on tests of attention (Trails A), executive function (Trails B), and visuospatial function (visual reproduction, Hooper visual organization), but not with performance on tests of verbal memory or naming. CONCLUSIONS: The Framingham Stroke Risk Profile may identify subjects with smaller brains and poorer cognitive function among stroke- and dementia-free subjects, reinforcing the importance of managing stroke risk factors.

Adult↗
PubMed2003

Effect of L-dopa on plasma homocysteine in PD patients: relationship to B-vitamin status.

BACKGROUND: The antiparkinsonian drug L-dopa causes increased cellular synthesis of homocysteine and consequent hyperhomocysteinemia in rats. This effect of L-dopa on plasma homocysteine is accentuated under conditions of impaired homocysteine metabolism such as folate deficiency. OBJECTIVE: To investigate the effect of L-dopa administration and B-vitamin status on plasma homocysteine concentrations in humans with PD. METHODS: Plasma homocysteine, folate, vitamin B(12), and pyridoxal-5'-phosphate (PLP) concentrations were determined in 40 individuals diagnosed with idiopathic PD who were being treated as outpatients at the Boston University Medical Center Neurology Clinic. Twenty of the patients were on L-dopa therapy (treatment group) and 20 were L-dopa-naive (control group). RESULTS: The mean plasma homocysteine concentration was higher in the treatment group than in the controls (p = 0.018). Plasma homocysteine was correlated with plasma folate, vitamin B(12), and PLP concentrations in the treatment group (p <or= 0.007) but not in the controls. CONCLUSION: L-Dopa can cause hyperhomocysteinemia in PD patients, the extent of which is influenced by B-vitamin status. The B-vitamin requirements necessary to maintain normal plasma homocysteine concentrations are higher in L-dopa-treated patients than in those not on L-dopa therapy. B-Vitamin supplements may be warranted for PD patients on L-dopa therapy.

Antiparkinson Agents↗
PubMed2003

Lower cognitive function in the presence of obesity and hypertension: the Framingham heart study.

OBJECTIVE: To determine the independent effects of obesity and hypertension on cognitive functioning. METHODS: Using a prospective design, male (n=551) and female (n=872) participants of the Framingham Heart Study were classified by presence or absence of obesity and hypertension based on data collected over an 18-y surveillance period. All subjects were free from dementia, stroke, and clinically diagnosed cardiovascular disease up to the time of cognitive testing. Statistical models were adjusted for age, education, occupation, cigarette smoking, alcohol consumption, total cholesterol, and a diagnosis of type II diabetes. Body mass index status (nonobese or obese) and blood pressure status (normotensive or hypertensive) were then related to cognitive performance (learning, memory, executive functioning, and abstract reasoning) on tests administered 4-6 y later. RESULTS: Adverse effects of obesity and hypertension on cognitive performance were observed for men only. Obese and hypertensive men performed more poorly than men classified as either obese or hypertensive, and the best performance was observed in nonobese, normotensive men. CONCLUSIONS: The adverse effects of obesity and hypertension in men are independent and cumulative with respect to cognitive deficit.

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PubMed2001

Elevated midlife blood pressure increases stroke risk in elderly persons: the Framingham Study.

BACKGROUND: Stroke risk predictions are traditionally based on current blood pressure (BP). The potential impact of a subject's past BP experience (antecedent BP) is unknown. We assessed the incremental impact of antecedent BP on the risk of ischemic stroke. METHODS: A total of 5197 stroke-free subjects (2330 men) in the community-based Framingham Study cohort were enrolled from September 29, 1948, to April 25, 1953, and followed up to December 31, 1998. We determined the 10-year risk of completed initial ischemic stroke for 60-, 70-, and 80-year-old subjects as a function of their current BP (at baseline), recent antecedent BP (average of readings at biennial examinations 1-9 years before baseline), and remote antecedent BP (average at biennial examinations 10-19 years earlier), with adjustment for smoking and diabetes mellitus. Models incorporating antecedent BP were also adjusted for baseline BP. The effect of each BP component (systolic BP, diastolic BP, and pulse pressure) was assessed separately. RESULTS: Four hundred ninety-one ischemic strokes (209 in men) were observed in eligible subjects. The antecedent BP influenced the 10-year stroke risk at the age of 60 years (relative risk per SD increment of recent antecedent systolic BP: women, 1.68 [95% confidence interval, 1.25-2.25]; and men, 1.92 [95% confidence interval, 1.39-2.66]) and at the age of 70 years (relative risk per SD increment of recent antecedent systolic BP: women, 1.66 [95% confidence interval, 1.28-2.14]; and men, 1.30 [95% confidence interval, 0.97-1.75]). This effect was evident for recent and remote antecedent BP, consistent in hypertensive and nonhypertensive subjects, and demonstrable for all BP components. CONCLUSIONS: Antecedent BP contributes to the future risk of ischemic stroke. Optimal prevention of late-life stroke will likely require control of midlife BP.

Adult↗
PubMed2001

Hemostatic state and atrial fibrillation (the Framingham Offspring Study).

Atrial fibrillation (AF) is strongly associated with thromboembolic complications, although the mechanism for the increased risk has not been fully explained. To determine whether AF might be associated with a hypercoagulable state, we studied hemostatic factors in subjects with or without AF in the Framingham Heart Study. In 3,577 subjects, we measured fibrinogen, von Willebrand factor antigen, tissue plasminogen activator (tPA) antigen, and plasminogen activator inhibitor-1 antigen. Forty-seven subjects had AF at the index clinic examination and 15 had AF on a prior examination, but not on the current examination. Before matching, the 47 subjects with prevalent AF had higher levels of fibrinogen, von Willebrand factor, and tPA antigen than those without AF, all p < or =0.03. Compared with 167 referent subjects matched for age, sex, and other risk factors, those with AF had higher tPA antigen levels than those without AF, 1 1.8 +/- 4.0 ng/ml versus 10.5 +/- 3.9 ng/ml (p = 0.04). However, when further stratified according to their cardiovascular disease status, the differences in hemostatic factors were no longer significant. We conclude that the prothrombotic profile associated with AF was explained by the risk factors of the subjects and the presence of cardiovascular disease. Nonetheless, the hemostatic changes may contribute toward the propensity for thromboembolic complications in AF. Further prospective studies are needed to evaluate whether measurement of these and other hemostatic factors will identify patients with AF who are at increased risk for thromboembolic complications, and who may therefore benefit from more intensive therapy.

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PubMed2001

Cerebrovascular and brain morphologic correlates of mild cognitive impairment in the National Heart, Lung, and Blood Institute Twin Study.

OBJECTIVE: To evaluate the relative risk (RR) of mild cognitive impairment (MCI) associated with cerebrovascular risk factors and cerebrovascular-related brain changes. DESIGN: Mild cognitive impairment was determined for the subjects of the prospective National Heart, Lung, and Blood Institute Twin Study. Quantitative measures of brain, white matter hyperintensity, cerebral infarction, apolipoprotein E genotype, and psychometric testing were obtained. RESULTS: Subjects with MCI were older (73.5 +/- 3.0 vs 72.1 +/- 2.8 years), consumed less alcohol (3.7 +/- 5.8 vs 7.0 +/- 10.7 drinks per week), had greater white matter hyperintensity volumes (0.56% +/- 0.82% vs 0.25% +/- 0.34% of cranial volume), and had an increased prevalence of apolipoprotein E4 genotype (31.4% vs 19.2%) than normal subjects. White matter hyperintensity and the presence of the apolipoprotein E4 genotype were associated with a significantly increased risk for MCI. When all subjects were included in the analysis, alcohol consumption was associated with a reduced risk for MCI (RR = 0.93, P<.05). When subjects with a history of symptomatic cerebrovascular disease were excluded from the analysis, elevated midlife diastolic blood pressure was associated with an increased risk for MCI (RR = 1.70, P<.05). CONCLUSIONS: Elevated midlife blood pressures, and the resulting increased white matter hyperintensities, increase the risk for MCI in a group of community-dwelling older men to at least the same degree as apolipoprotein E4 genotype. Given the common occurrence of elevations in midlife blood pressure, early and effective treatment may be warranted to prevent late-life brain abnormalities and MCI. Moreover, since many individuals with MCI progress to clinical dementia, longitudinal evaluations of this cohort will be important.

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PubMed2001

Prevention of strokes.

Stroke is a major cause of morbidity and mortality. Risk factors for stroke have been determined through prospective epidemiologic study. Control of risk factors has been demonstrated to reduce stroke incidence, either through controlled trials or inferred from observational studies. In the past few years, new approaches to the treatment of established risk factors have been discovered. These include aggressive control of hypertension in diabetes patients, prevention of type 2 diabetes through lifestyle modification, carotid endarterectomy for moderate symptomatic carotid stenosis, encouragement of a high level of physical activity, and control of abdominal obesity and elevated body mass index. In addition, new strategies for stroke prevention have been identified, including encouragement of a diet high in fruits, vegetables, whole grains, and omega-3 fatty acids, the use of vitamins B12, B6, and folic acid in hyperhomocysteinemia, and moderate alcohol consumption. Clinical trial data support the use of hydroxy-methyl-coenzyme A inhibitors in patients with coronary artery disease, and ramipril in high-risk patients with coronary artery disease and diabetes, for the primary prevention of stroke. New risk factors for stroke are being investigated, including the role of chronic inflammation and infection, and these may provide future strategies for stroke prevention.

Humans↗
PubMed2001

Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study.

BACKGROUND: The role of C-reactive protein (CRP) as a novel plasma marker of atherothrombotic disease is currently under investigation. Previous studies have mostly related CRP to coronary heart disease, were often restricted to a case-control design, and failed to include pertinent risk factors to evaluate the joint and net effect of CRP on the outcome. We related plasma CRP levels to incidence of first ischemic stroke or transient ischemic attack (TIA) in the Framingham Study original cohort. METHODS: There were 591 men and 871 women free of stroke/TIA during their 1980 to 1982 clinic examinations, when their mean age was 69.7 years. CRP levels were measured by using an enzyme immunoassay on previously frozen serum samples. Analyses were based on sex-specific CRP quartiles. Risk ratios (RRs) were derived, and series of trend analyses were performed. RESULTS: During 12 to 14 years of follow-up, 196 ischemic strokes and TIAs occurred. Independent of age, men in the highest CRP quartile had 2 times the risk of ischemic stroke/TIA (RR=2.0, P=0.027), and women had almost 3 times the risk (RR=2.7, P=0.0003) compared with those in the lowest quartile. Assessment of the trend in risk across quartiles showed unadjusted risk increase for men (RR=1.347, P=0.0025) and women (RR=1.441, P=0.0001). After adjustment for smoking, total/HDL cholesterol, systolic blood pressure, and diabetes, the increase in risk across CRP quartiles remained statistically significant for both men (P=0.0365) and women (P=0.0084). CONCLUSIONS: Independent of other cardiovascular risk factors, elevated plasma CRP levels significantly predict the risk of future ischemic stroke and TIA in the elderly.

Adult↗
PubMed2000

Biobehavioral characteristics of nondemented older adults with subclinical brain atrophy.

OBJECTIVE: To characterize the risk factors and neuropsychological performance of two subgroups of community-dwelling, white elderly men free of severe cognitive impairment (n = 383; mean age, 72.9 +/- 3.0 years) who differ on volumetric measurements of total brain parenchyma and white matter hyperintensity (WMH) volumes. METHODS: Group comparisons were made of cerebrovascular disease risk factors measured at the time of imaging and at three prior examinations extending over 25 years of adult life. Measures of verbal memory and speed psychomotor processing at the time of imaging and 10 years before imaging were also available. RESULTS: Compared with those in the "nonatrophy" group, individuals in the subgroup with "atrophy" (defined by low total brain volume and high WMH volume) were older, reported a higher level of depressive symptomatology, experienced a steeper decline in diastolic blood pressure (DBP) and a steeper increase in pulse pressure, were less physically active, had smoked for more years, and had a higher prevalence of several cardiovascular disease indicators, including an ankle/arm systolic blood pressure ratio less than 0.9, and hypertension. After multivariate analysis, the 25-year decline in DBP, the number of years smoked, and an ankle/arm index of less than 0.9 remained significant discriminators of the two groups. Lower levels of speeded performance at the time of imaging and a steeper 10-year decline in cognitive performance on selected tests were also observed in the atrophic group. CONCLUSION: Community-dwelling older adults with volumetric brain measurements associated with accelerated aging are distinguishable on the basis of several health-related characteristics. These individuals also perform less well on certain tasks involving executive functioning.

Adult↗
PubMed2000

Contribution of genetic and environmental influences to ankle-brachial blood pressure index in the NHLBI Twin Study. National Heart, Lung, and Blood Institute.

The ankle-brachial index (ABI) is widely used in the clinical diagnosis of peripheral arterial disease. The contributions of genetic and environmental influences to normal and abnormal ABI values are unknown. In this study, the authors used available data on 94 monozygotic pairs and 90 dizygotic pairs of elderly, White, male twins examined in 1995-1997 to investigate the contributions of genetic and environmental influences to normative ABI values. Within-twin-pair correlations for normative ABI values were statistically significant, and the correlation in monozygotic twin pairs was significantly greater than that in dizygotic pairs. Structural equation modeling of the variance-covariance matrices of monozygotic and dizygotic twins indicated that 48% of the observed variability in ABI values could be attributed to additive genetic effects. In contrast, concordance rates for low ABI values (ABI< or =0.9) for both monozygotic and dizygotic twins were significantly greater than would be expected by chance alone, but within-pair monozygotic similarity was not significantly greater than dizygotic similarity. A matched-cotwin analysis in 21 pairs that were discordant for low ABI values found that twins with low ABI values were physically less active and more likely to be persistent smokers than their normal-control brothers. These findings reinforce the role of individual health practices (e.g., physical activity, smoking) in the manifestation of peripheral arterial disease among subjects matched for age, genetics, and early shared environment.

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PubMed2000

The preclinical phase of alzheimer disease: A 22-year prospective study of the Framingham Cohort.

OBJECTIVES: To relate performance on tests of cognitive ability to the subsequent development of probable Alzheimer disease (pAD) and to identify the pattern of earliest changes in cognitive functioning associated with a diagnosis of pAD. DESIGN: From May 1975 to November 1979, a screening neuropsychological battery was administered to Framingham Study participants. They were followed up prospectively for 22 years and examined at least every 2 years for the development of pAD. SETTING: A community-based center for epidemiological research. PARTICIPANTS: Subjects were 1076 participants of the Framingham Study aged 65 to 94 years who were free of dementia and stroke at baseline (initial) neuropsychological testing. MAIN OUTCOME MEASURE: Presence or absence of pAD during a 22-year surveillance period was related to test performance at initial neuropsychological testing. RESULTS: Lower scores for measures of new learning, recall, retention, and abstract reasoning obtained during a dementia-free period were associated with the development of pAD. Lower scores for measures of abstract reasoning and retention predicted pAD after a dementia-free period of 10 years. CONCLUSIONS: The "preclinical phase" of detectable lowering of cognitive functioning precedes the appearance of pAD by many years. Measures of retention of information and abstract reasoning are among the strongest predictors of pAD when the interval between initial assessment and the development of pAD is long. Arch Neurol. 2000.

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PubMed2000

Ten-year follow-up for male twins divided into high- or low-risk groups for ischemic heart disease based on risk factors measured 25 years previously.

PURPOSE: To undertake medical follow-up in white males in the National Heart, Lung, and Blood Institute (NHLBI) twin study, previously divided on the basis of cardiovascular disease risk factors. METHODS: Tree structured survival analysis (TSSA) used at a mean age of 63 years to classify twins into high and low risk subgroups for ischemic heart disease (IHD) found that subjects at a mean age of 48 years were at highest risk with high systolic blood pressures and low high density lipoprotein cholesterol levels. Low risk subjects had lower blood pressures, better pulmonary function tests, and a negative family history for IHD or low post load plasma glucose levels. Medical record review was performed ten years later at the 4th Examination of the NHLBI twin cohort conducted in 1995-1997. RESULTS: The percentage of men in the NHLBI twin study who died nearly tripled (from 9.3% to 25.8%) in the ten-year period between the ages of 63 and 73 years. Deaths have tended to remain higher in DZ than MZ twins (27.8% versus 23.7%). At Exam 4, the relative risk of IHD (fatal or non-fatal) was 5.24 times higher for those in the high risk group than those in the low risk class (95% confidence limit 2.72-10.07, p < 0.0001 and 5.86 for any cardiovascular disease (95% confidence limit 3.03-11.33). The proportion of deaths from IHD in subjects with a high risk profile at entry was 51.7%, and 70.0% had died from all cardiovascular related disease. CONCLUSION: The present results indicate TSSA remained effective in classifying subjects into subgroups with greater risk of morbidity and mortality related to cardiovascular disease after ten additional years.

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PubMed2000

Longitudinal changes in the contribution of genetic and environmental influences to symptoms of depression in older male twins.

Genetically informative longitudinal data on self-reported symptoms of depression allow for an investigation of the causes of stability and change in depression symptoms throughout adult life. In this report, the authors investigated the relative contribution of genetic and environmental influences to symptoms of depression in 83 monozygotic and 84 dizygotic male twin pairs from the National Heart, Lung, and Blood Institute (NHLBI) Twin Study. Participants first completed the Center for Epidemiologic Studies-Depression (CES-D) scale in 1985-1986 and again during 1995-1997. Mean age of twins at baseline was 63 years, range 59 to 70. From cross-sectional genetic analyses we estimated the heritability of CES-D to be 25% (95% confidence interval [CI], 11%-39%) at baseline and 55% (95% CI, 40%-71%) at follow-up. Fitting longitudinal genetic models to the two-wave data, we found that stability of symptoms over the 10-year follow-up was due primarily to continuity of genetic influences.

Adult↗
PubMed2000

The contribution of genetic influences to measures of lower-extremity function in older male twins.

Tests of balance, gait, and endurance were administered to 95 monozygotic (MZ) and 92 dizygotic (DZ), white male twins aged 68 to 79 years who had been born in the United States. Within-twin-pair correlations were calculated for each individual task and for an overall summary performance score. These were subjected to structural equation modeling to determine the contributions of genetic and environmental influences to individual differences in performance scores. MZ intraclass correlations were significant and greater than DZ correlations for the 8-foot walk and the repeated chair stands task, but not for the standing balance task. The heritability of the lower-extremity summary score was 57%, of which 39% was due to additive genetic effects and 18% due to nonadditive effects. In addition, we found that genetic influences contributed primarily to twin similarity in the poorest quartile of performance, whereas shared environmental influences contributed to twin similarity in the best quartile.

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