Prevalence of Parkinson's disease across North America.

Estimates of the prevalence of Parkinson's disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson's disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1). US Medicare program data provided complementary estimates for the corresponding regions. Using our age- and sex-specific meta-estimates from California, Minnesota, and Ontario and the US population structure from 2010, we estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000 (95% confidence interval 537-614) that there were 680,000 individuals in the US aged ≥45 years with PD in 2010 and that that number will rise to approximately 930,000 in 2020 and 1,238,000 in 2030 based on the US Census Bureau population projections. Regional variations in prevalence were also observed in both the project results and the Medicare-based calculations with which they were compared. The estimates generated by the Hawaiian study were lower across age categories. These estimates can guide health-care planning but should be considered minimum estimates. Some heterogeneity exists that remains to be understood.

Marinesco bodies and substantia nigra neuron density in Parkinson's disease.

AIM: Marinesco bodies (MB) are intranuclear inclusions in pigmented neurons of the substantia nigra (SN). While rare in children, frequency increases with normal ageing and is high in Alzheimer's disease, dementia with Lewy bodies and other neurodegenerative disorders. Coinciding with the age-related rise in MB frequency is initiation of cell death among SN neurons. Whether MB have a role in this process is unknown. Our aim is to examine the association of MB with SN neuron density in Parkinson's disease (PD) in the Honolulu-Asia Aging Study. METHODS: Data on MB and neuron density were measured in SN transverse sections in 131 autopsied men aged 73-99 years at the time of death from 1992 to 2007. RESULTS: Marinesco body frequency was low in the presence vs. absence of PD (2.3% vs. 6.6%, P < 0.001). After PD onset, MB frequency declined as duration of PD increased (P = 0.006). Similar patterns were observed for SN neuron density. When MB frequency was low, neuron density was noticeably reduced in the SN ventrolateral quadrant, the region most vulnerable to PD neurodegeneration. Low MB frequency was unique to PD as its high frequency in non-PD cases was unrelated to parkinsonian signs and incidental Lewy bodies. Frequency was high in the presence of Alzheimer's disease and apolipoprotein ε4 alleles. CONCLUSIONS: While findings confirm that MB frequency is low in PD, declines in MB frequency continue with PD duration. The extent to which MB have a distinct relationship with PD warrants clarification. Further studies of MB could be important in understanding PD processes.

Fruit and vegetable intake and mortality from cardiovascular disease in Japan: a 24-year follow-up of the NIPPON DATA80 Study.

BACKGROUND/OBJECTIVES: There have been few studies on the association of fruit and vegetable (FV) intake with cardiovascular disease (CVD) risk in Asian populations where both dietary habits and disease structure are different from western countries. No study in Asia has found its significant association with stroke. We examined associations of FV intake with mortality risk from total CVD, stroke and coronary heart diseases (CHDs) in a representative Japanese sample. METHODS: A total of 9112 participants aged from 24-year follow-up data in the NIPPON DATA80, of which baseline data were obtained in the National Nutrition Survey Japan in 1980, were studied. Dietary data were obtained from 3-day weighing dietary records. Participants were divided into sex-specific quartiles of energy adjusted intake of FV. Multivariate-adjusted hazard ratios (HRs) were calculated between strata of the total of FV intake, fruit intake and vegetable intake. The adjustment included age, sex, smoking, drinking habit and energy adjusted intakes of sodium and some other food groups. RESULTS: Participants with higher FV intake were older, ate more fish, milk and dairy products and soybeans and legumes and ate less meat. Multivariate-adjusted HR (95% confidence interval; P; P for trend) for the highest versus the lowest quartile of the total of FV intake was 0.74 (0.61-0.91; 0.004; 0.003) for total CVD, 0.80 (0.59-1.09; 0.105; 0.036) for stroke and 0.57 (0.37-0.87; 0.010; 0.109) for CHD. CONCLUSIONS: The results showed that higher total intake of FVs was significantly associated with reduced risk of CVD mortality in Japan.

Trend of stroke incidence in a Japanese population: Takashima stroke registry, 1990-2001.

BACKGROUND: In Japan, stroke mortality and incidence started to decline during the 1960s. The recent unfavourably diverging trends in risk factors make it uncertain whether the decline will continue. Few comprehensive stroke registries of long research duration exist in Japan to illustrate the trends in stroke incidence. OBJECTIVE: We examined 12-year stroke registration data to evaluate the current trend in a Japanese population. METHODS: Data were obtained from the Takashima Stroke Registry, covering approximately 55 000 residents of Takashima County in central Japan. We calculated the age-adjusted stroke incidence rates (/100 000 person-years) and 95% confidence intervals for 1990-1992, 1993-1995, 1996-1998, and 1999-2001. We applied the direct method to adjust for the age distribution among the four periods. The incidence time trend was determined by calculating the average annual change across the study years using negative binomial regression analysis. RESULTS: There were 1453 (men: 771 and women: 682) registered first-ever stroke cases during 1990-2001. The diagnosis was established by neuro-imaging in 93.6% of the cases. The average age was 69.4 years in men and 74.2 years in women. The age-adjusted incidence rates of stroke across the four observation periods were 143.1 (confidence interval: 127.4-158.8) in 1990-1992, 147.4 (confidence interval: 131.9-162.8) in 1993-1995, 120.4 (confidence interval: 106.7-134.0) in 1996-1998, and 122.9 (confidence interval: 109.6-136.2) in 1999-2001. The stroke incidence across the study years showed an insignificant time trend, with an average annual change of -0.33% (confidence interval: -2.44 to 1.78) per year. Similar trends were observed for both men and women and stroke subtypes. CONCLUSIONS: The previously reported declining trend in stroke incidence may have levelled off or slowed down considerably in the Japanese population.

Morning surge in circadian periodicity of ischaemic stroke is independent of conventional risk factor status: findings from the Takashima Stroke Registry 1990-2003.

BACKGROUND: We examined the circadian periodicity of ischaemic stroke (IS) onset and its relationship with conventional risk factors using 14-year stroke registration data. METHODS: Ischaemic stroke event data were acquired from the Takashima Stroke Registry, which covers a stable population of approximately 55,000 in Takashima County in central Japan. During 1990-2003 there were 637 (353 men and 284 women) cases with classifiable onset time. IS incidence was categorized as occurring at night (midnight to 6 am), morning (6 am to noon), afternoon (noon to 6 pm), and evening (6 pm to midnight). The OR (with 95% CI) of having an IS in the morning, afternoon, and evening were calculated, with night serving as reference. RESULTS: There was significant diurnal variation in IS incidence (P < 0.001). The proportion of events was highest in the morning (40.7; 95% CI: 36.9-44.5), and lowest in the night (14.0; 95% CI: 11.5-16.9). In the morning an excess incidence of IS was observed in both genders, in subjects <65 years and > or =65 years, and in all IS subtypes. The morning excess of IS incidence was similar across seasons and days of the week. For all IS, morning excess was higher (odds ratio: 2.91; 95% CI: 2.29-3.70) compared to the night period. Similar trends persisted after adjusting for age, gender, and risk factors. CONCLUSION: In the examination of circadian variation of IS onset, a predominant morning peak independent of conventional risk factors was observed in a Japanese population with similar pattern across seasons of the year and days of the week.

Serum estradiol and risk of stroke in elderly men.

OBJECTIVE: To determine if levels of serum estradiol and testosterone can predict stroke in a population-based sample of elderly men. METHODS: Serum 17beta estradiol and testosterone were measured in 2,197 men aged 71 to 93 years who participated in the Honolulu-Asia Aging Study from 1991 to 1993. All were free of prevalent stroke, coronary heart disease, and cancer. Participants were followed to the end of 1998 for thromboembolic and hemorrhagic events. RESULTS: During the course of follow-up, 124 men developed a stroke (9.1/1,000 person-years). After age adjustment, men in the top quintile of serum estradiol (> or =125 pmol/L [34.1 pg/mL]) experienced a twofold excess risk of stroke vs men whose estradiol levels were lower (14.8 vs 7.3/1,000 person-years, p < 0.001). Among the lower quintiles, there were little differences in the risk of stroke. Findings were also significant and comparable for bioavailable estradiol and for thromboembolic and hemorrhagic events. After additional adjustment for hypertension, diabetes, adiposity, cholesterol concentrations, atrial fibrillation, and other characteristics, men in the top quintile of serum estradiol continued to have a higher risk of stroke vs those whose estradiol levels were lower (relative hazards = 2.2; 95% CI = 1.5 to 3.4, p < 0.001). Testosterone was not related to the risk of stroke. CONCLUSIONS: High levels of serum estradiol may be associated with an elevated risk of stroke in elderly men.

Excessive daytime sleepiness and subsequent development of Parkinson disease.

OBJECTIVE: To determine if excessive daytime sleepiness (EDS) can predate future Parkinson disease (PD). METHODS: EDS was assessed in 3,078 men aged 71 to 93 years in the Honolulu-Asia Aging Study from 1991 to 1993. All were free of prevalent PD and dementia. Follow-up for incident PD was based on three repeat neurologic assessments from 1994 to 2001. RESULTS: During the course of follow-up, 43 men developed PD (19.9/10,000 person-years). After age adjustment, there was more than a threefold excess in the risk of PD in men with EDS vs men without EDS (55.3 vs 17.0/10,000 person-years; odds ratio [OR] = 3.3; 95% CI = 1.4 to 7.0; p = 0.004). Additional adjustment for insomnia, cognitive function, depressed mood, midlife cigarette smoking and coffee drinking, and other factors failed to alter the association between EDS and PD (OR = 2.8; 95% CI = 1.1 to 6.4; p = 0.014). Other sleep related features such as insomnia, daytime napping, early morning grogginess, and frequent nocturnal awakening showed little relation with the risk of PD. CONCLUSIONS: Excessive daytime sleepiness may be associated with an increased risk of developing Parkinson disease.

Consumption of milk and calcium in midlife and the future risk of Parkinson disease.

OBJECTIVE: To examine the relation between milk and calcium intake in midlife and the risk of Parkinson disease (PD). METHODS: Findings are based on dietary intake observed from 1965 to 1968 in 7,504 men ages 45 to 68 in the Honolulu Heart Program. Men were followed for 30 years for incident PD. RESULTS: In the course of follow-up, 128 developed PD (7.1/10,000 person-years). Age-adjusted incidence of PD increased with milk intake from 6.9/10,000 person-years in men who consumed no milk to 14.9/10,000 person-years in men who consumed >16 oz/day (p = 0.017). After further adjustment for dietary and other factors, there was a 2.3-fold excess of PD (95% CI 1.3 to 4.1) in the highest intake group (>16 oz/day) vs those who consumed no milk. The effect of milk consumption on PD was also independent of the intake of calcium. Calcium from dairy and nondairy sources had no apparent relation with the risk of PD. CONCLUSIONS: Findings suggest that milk intake is associated with an increased risk of Parkinson disease. Whether observed effects are mediated through nutrients other than calcium or through neurotoxic contaminants warrants further study.

Prevalence and correlates of orthostatic hypotension in middle-aged men and women in Korea: the Korean Health and Genome Study.

To examine the prevalence and correlates of orthostatic hypotension (OH) in middle-aged adults enrolled in the Korean Health and Genome Study. Participants were 8908 individuals aged 40-69 years. Supine blood pressure (BP) was measured three times at 30-s intervals after at least 5 min of rest in the supine position and single standing BP was measured at 0 and 2 min after standing, respectively. OH was defined as a reduction in systolic BP or diastolic BP > or = 20 and 10 mmHg, respectively. The prevalence of OH at 0 and 2 min after standing was 12.3 and 2.9%, respectively. At 0 min of standing, OH frequency increased significantly with age from 6.4% in those aged 40-44 years to 23.1% in those aged 65-69 (P < 0.001). After adjustment for age and other characteristics, hypertension was associated with a 1.7-fold excess in the odds of OH in men and a 1.6-fold excess in women (P < 0.001). In contrast, an increase in body mass index (BMI) on the order of 5 kg/m2 was associated with a 20-30% reduction in the odds of OH (P < 0.001). Diabetes in women was also associated with a 1.4-fold excess in the odds of OH (P < 0.05). An increase in triglyceride by 136 mg/dl in men was associated with an increase in the odds of OH (P < 0.05). In conclusion, the prevalence and correlates of OH other than diabetes and triglycerides were notably similar in men and women. While the association between hypertension and OH has been observed elsewhere, low BMI in Korean adults with OH may be an important marker for subclinical morbidity or coexisting risk factors that need to be identified.

A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly.

High density lipoprotein cholesterol (HDL-C) levels are inversely associated with the incidence of coronary heart disease (CHD) in middle-aged individuals; in the elderly, the association is less clear. Genetic factors, including variations in the cholesteryl ester transfer protein (CETP) gene, play a role in determining HDL-C levels. Controversy remains about whether CETP deficiency and the resultant rise in HDL-C are antiatherogenic, or whether CETP has the opposite effect due to its role in reverse cholesterol transport. In a seven-year follow-up of 2340 men aged 71-93 in the Honolulu Heart Program, the age-adjusted CHD incidence rates were significantly lower in men with high versus low HDL-C levels. After adjustment for age, hypertension, smoking, and total cholesterol, the relative risk of CHD for those with HDL-C levels >or=60 mg/dl, compared with those with HDL-C levels <40 mg/dl, was 0.6. Men with a CETP mutation had the lowest rates of CHD, although this was not statistically significant. These data indicate that HDL-C remains an important risk factor for CHD in the elderly. Whether a CETP mutation offers additional protection against CHD warrants further investigation.

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.

Midlife adiposity and the future risk of Parkinson's disease.

BACKGROUND: Evidence suggests that nigrostriatal system disorders are associated with PD and adiposity. Whether patterns of adiposity coexist or predate clinical PD is unknown. This report examines the relation between midlife adiposity and the risk of PD. METHODS: Measurement of adiposity occurred from 1965 to 1968 in 7,990 men in the Honolulu Heart Program (aged 45 to 68 years and without PD). Adiposity measures included body mass index (BMI), subscapular skinfold thickness (SSF), and triceps skinfold thickness (TSF). Follow-up for incident PD occurred over a 30-year period. RESULTS: During the course of follow-up, PD was observed in 137 men. Among the measures of adiposity, age-adjusted incidence of PD increased threefold from 3.7/10,000 person-years in the bottom quartile of TSF (1 to 5 mm) to 11.1/10,000 person-years in the top quartile (11 to 32 mm, p < 0.001). Effects of TSF on PD were independent of cigarette smoking, coffee consumption, physical activity, daily caloric and fat intake, and the other measures of adiposity (p < 0.001). Whereas rates of PD were lowest in the bottom quartile of BMI and SSF vs higher quartiles, associations with PD were weaker than they were for TSF. The effect of TSF on clinical onset before age 65 years was similar to the effect that was observed in later life. CONCLUSIONS: Increased triceps skinfold thickness measured in midlife is associated with an elevated risk of future PD. Whether patterns of adiposity reflect a unique metabolic pathology in individuals at a high risk of PD warrants further study.

Preadolescent predictors of substance initiation: a test of both the direct and mediated effect of family social control factors on deviant peer associations and substance initiation.

A review of the literature suggests that early substance initiation is related to a variety of negative outcomes, including substance misuse or abuse in adolescence and adulthood. This study examines potentially modifiable predictors of early substance initiation, including both family and peer factors known to influence early initiation. A theoretically derived model of substance initiation was tested using structural equation modeling. Results indicate that both family and peer factors have an impact on early substance initiation when children in this sample were 11 and 12 years old. The model explained 60% of the variance in substance initiation. Prosocial family processes (rules, monitoring, and attachment) had a significant impact on child peer association, decreasing involvement with antisocial peers. These prosocial family processes had a significant negative effect on substance initiation even while modeling the influence of antisocial peers. Implications for drug use prevention practice are discussed.

Assessing the effects of a school-based intervention on unscheduled school transfers during elementary school.

Raising Healthy Children is a cluster-randomized study of a school-based intervention aimed at preventing problem behaviors among children recruited into the project in the first or second grade of elementary school. Multilevel analysis was used to compare students in intervention and control schools with respect to whether they transferred out of their original schools. Students in intervention schools were less likely to transfer within the first 5 years of the project. A multilevel discrete-time survival model that included both time-varying and contextual variables revealed that the difference in hazard of transfer was greatest in the earlier years of the project.

Ankle-brachial blood pressure in elderly men and the risk of stroke: the Honolulu Heart Program.

Although low ankle/brachial blood pressure index (ABI) is a marker of generalized atherosclerosis in the elderly, it has not been identified as a risk factor for stroke. The purpose of this report is to examine the relation between ABI and stroke in elderly men. ABI was measured from 1991 to 1993 in 2767 men aged 71 to 93 years in the Honolulu Heart Program without a history of stroke and coronary heart disease. Subjects were followed for 3 to 6 years for fatal and nonfatal thromboembolic and hemorrhagic stroke. During follow-up, there were 91 strokes. There was an age-adjusted 2-fold excess in men with an ABI < 0.9 (6.0%) versus men with an ABI > or = 0.9 (2.9%, P < 0.01). Thromboembolic events occurred in 4.6% of men with an ABI < 0.9 and in 2.0% in those with an ABI > or = 0.9 (P < 0.01). Hemorrhagic stroke was also more frequent in men with a low ABI (< 0.9) versus a higher ABI (1.9 vs. 0.8%, respectively). After adjusting for other factors, the risk of total and thromboembolic strokes increased with declining ABI (P = 0.019 and P = 0.004, respectively). The relation between ABI and stroke was similar and statistically significant in the presence and absence of diabetes and hypertension (P < 0.05). Findings suggest that ABI is inversely related to the incidence of stroke. Simple measurement of ABI in an outpatient setting could be an important tool for assessing the risk of stroke in the elderly.

Frequency of bowel movements and the future risk of Parkinson's disease.

BACKGROUND: Constipation is frequent in PD, although its onset in relation to clinical PD has not been well described. Demonstration that constipation can precede clinical PD could provide important clues to understanding disease progression and etiology. The purpose of this report is to examine the association between the frequency of bowel movements and the future risk of PD. METHODS: Information on the frequency of bowel movements was collected from 1971 to 1974 in 6790 men aged 51 to 75 years without PD in the Honolulu Heart Program. Follow-up for incident PD occurred over a 24-year period. RESULTS: Ninety-six men developed PD an average of 12 years into follow-up. Age-adjusted incidence declined consistently from 18.9/10,000 person-years in men with <1 bowel movement/day to 3.8/10,000 person-years in those with >2/day (p = 0.005). After adjustment for age, pack-years of cigarette smoking, coffee consumption, laxative use, jogging, and the intake of fruits, vegetables, and grains, men with <1 bowel movement/day had a 2.7-fold excess risk of PD versus men with 1/day (95% CI: 1.3, 5.5; p = 0.007). The risk of PD in men with <1 bowel movement/day increased to a 4.1-fold excess when compared with men with 2/day (95% CI: 1.7, 9.6; p = 0.001) and to a 4.5-fold excess versus men with >2/day (95% CI: 1.2, 16.9; p = 0.025). CONCLUSIONS: Findings indicate that infrequent bowel movements are associated with an elevated risk of future PD. Further study is needed to determine whether constipation is part of early PD processes or is a marker of susceptibility or environmental factors that may cause PD.

beta(2)-Glycoprotein 1-dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction: the honolulu heart program.

BACKGROUND: It has been hypothesized that immunoreactivity to beta(2)-glycoprotein 1 (beta2GP1)-dependent anticardiolipin antibody (aCL), but not beta2GP1-independent aCL, is associated with increased risk of ischemic stroke and myocardial infarction (MI). METHODS: We performed a nested case-control study examining aCL as a risk factor for ischemic stroke and MI by using stored frozen sera obtained from subjects enrolled in the Honolulu Heart Program and followed for up for 20 years. We measured beta2GP1-dependent and beta2GP1-independent aCL and anti-beta2GP1 immunoreactivity in 259 men who developed an ischemic stroke, in 374 men who developed an MI, and in a control group of 1360 men who remained free of both conditions. RESULTS: Only beta2GP1-dependent aCL of the IgG class was significantly associated with both incident ischemic stroke and MI. This association was attenuated in the last 5 years of the 20-year follow-up. For stroke, the risk factor-adjusted relative odds for men with a positive versus a negative beta2GP1-dependent aCL of the IgG class were 2.2 (95% CI 1.5 to 3.4) at 15 years and 1.5 (95% CI 1.0 to 2.3) at 20 years. For MI, the adjusted relative odds were 1.8 (95% CI 1.2 to 2.6) at 15 years and 1.5 (95% CI 1.1 to 2.1) at 20 years. CONCLUSIONS: These data suggest that aCL IgG, particularly the beta2GP1-dependent variety, is an important predictor of future stroke and MI in men.

fMRI auditory language differences between dyslexic and able reading children.

During fMRI, dyslexic and control boys completed auditory language tasks (judging whether pairs of real and/or pseudo words rhymed or were real words) in 30 s 'on' conditions alternating with a 30 s 'off' condition (judging whether tone pairs were same). During phonological judgment, dyslexics had more activity than controls in right than left inferior temporal gyrus and in left precentral gyrus. During lexical judgment, dyslexics were less active than controls in bilateral middle frontal gyrus and more active than controls in left orbital frontal cortex. Individual dyslexics were reliably less active than controls in left insula and left inferior temporal gyrus. Dyslexic and control children differ in brain activation during auditory language processing skills that do not require reading.

The social predictors of adolescent alcohol misuse: a test of the social development model.

OBJECTIVE: This study was conducted to investigate the ability of the social development model (SDM) to predict alcohol misuse at age 16 and to investigate the ability of the SDM to mediate the effects of alcohol use at age 14 on alcohol misuse at age 16. METHOD: The sample of 807 (411 males) is from the longitudinal panel of the Seattle Social Development Project which, in 1985, surveyed all consenting fifth-grade students from 18 elementary schools serving high-crime neighborhoods in Seattle, Washington. Alcohol use was measured at age 14, predictors of alcohol misuse were measured at age 15 and alcohol misuse was measured at age 16. Structural equation modeling was used to examine the fit of the model to the data. RESULTS: All factor loadings were highly significant and the measurement model achieved a good fit with the data (Comparative Fit Index [CFI] = 0.93). A second-order structural model fit the data well (CFI = 0.91) and also explained 45% of the variance in alcohol misuse at age 16. The SDM partially and significantly mediated the direct effect of age-14 alcohol use on age-16 alcohol misuse. CONCLUSIONS: The risk and protective processes specified by the SDM serve as potential targets for the prevention or reduction of adolescent alcohol misuse.

Childhood and adolescent predictors of alcohol abuse and dependence in young adulthood.

OBJECTIVE: To provide a comprehensive examination of childhood and adolescent predictors of alcohol abuse and dependence at age 21, theoretically guided by the social development model. METHOD: Data were taken from an ethnically diverse urban sample of 808 students (51% male), surveyed at age 10 and followed prospectively to age 21 in 1996. Potential predictors of alcohol abuse and dependence at age 21 were measured at ages 10, 14 and 16. Relationships between these predictors and alcohol abuse and dependence were examined at each age, to assess changes in their patterns of prediction over time. RESULTS: Strong bonding to school, close parental monitoring of children and clearly defined family rules for behavior, appropriate parental rewards for good behaviors, high level of refusal skills and strong belief in the moral order predicted a lower risk for alcohol abuse and dependence at age 21. Of these, strong bonding to school consistently predicted lower alcohol abuse and dependence from all three ages (10, 14 and 16). By contrast, youths who had a higher risk of alcohol abuse and dependence at age 21 engaged in more problem behaviors, had more opportunities to be involved with antisocial individuals and spent more time with and were more bonded to those individuals, viewed fewer negative consequences from antisocial behaviors and held more favorable views on alcohol use. Of these, prior problem behaviors and antisocial opportunities and involvements at ages 10, 14 and 16 consistently predicted alcohol abuse and dependence at age 21. CONCLUSIONS: These important malleable predictors, identifiable as early as age 10, provide potential intervention targets for the prevention of alcohol abuse and dependence in early adulthood.