James C. Anthony

Inverse association of anti‐inflammatory treatments and Alzheimer's disease Initial results of a co‐twin control study

We conducted a co-twin control study among 50 elderly twin pairs with onsets of Alzheimers disease (AD) separated by 3 or more years. Twenty-three male pairs (46%) were screened from the (U.S.) National Academy of Sciences-National Research Council Registry (NAS-NRC Registry) of World War II veteran twins; others (mostly women) had responded to advertisements or were referred from AD clinics. Twenty-six pairs (52%) were monozygous. The onset of AD was inversely associated with prior use of corticosteroids or ACTH (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.06 to 0.95; p = 0.04). Similar but weaker trends were present among pairs discordant for history of arthritis or for prior daily use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin. The association was strongest when we combined use of steroids/ACTH or NSAIDs post hoc into a single variable of anti-inflammatory drugs (AIs) (OR, 0.24; CI, 0.07 to 0.74; p = 0.01). The inverse relation was strong in female (volunteer) twin pairs but was not present in the younger men from the NAS-NRC Registry. AIs had typically been taken for arthritis or related conditions, but a similar result was apparent after controlling statistically for the arthritis variable (OR, 0.08; CI, 0.01 to 0.69; p = 0.02). AIs have been proposed as a means of retarding the progression of AD symptoms, and these data suggest that AIs may also prevent or delay the initial onset of AD symptoms. Because of limitations in the case-control method, our results require corroboration with hypothesis-driven research designed to control bias and confounding.

Toward a global view of alcohol, tobacco, cannabis, and cocaine use: findings from the WHO World Mental Health Surveys

Background Alcohol, tobacco, and illegal drug use cause considerable morbidity and mortality, but good cross-national epidemiological data are limited. This paper describes such data from the first 17 countries participating in the World Health Organizations (WHOs) World Mental Health (WMH) Survey Initiative. Methods and Findings Household surveys with a combined sample size of 85,052 were carried out in the Americas (Colombia, Mexico, United States), Europe (Belgium, France, Germany, Italy, Netherlands, Spain, Ukraine), Middle East and Africa (Israel, Lebanon, Nigeria, South Africa), Asia (Japan, Peoples Republic of China), and Oceania (New Zealand). The WHO Composite International Diagnostic Interview (CIDI) was used to assess the prevalence and correlates of a wide variety of mental and substance disorders. This paper focuses on lifetime use and age of initiation of tobacco, alcohol, cannabis, and cocaine. Alcohol had been used by most in the Americas, Europe, Japan, and New Zealand, with smaller proportions in the Middle East, Africa, and China. Cannabis use in the US and New Zealand (both 42%) was far higher than in any other country. The US was also an outlier in cocaine use (16%). Males were more likely than females to have used drugs; and a sex–cohort interaction was observed, whereby not only were younger cohorts more likely to use all drugs, but the male–female gap was closing in more recent cohorts. The period of risk for drug initiation also appears to be lengthening longer into adulthood among more recent cohorts. Associations with sociodemographic variables were consistent across countries, as were the curves of incidence of lifetime use. Conclusions Globally, drug use is not distributed evenly and is not simply related to drug policy, since countries with stringent user-level illegal drug policies did not have lower levels of use than countries with liberal ones. Sex differences were consistently documented, but are decreasing in more recent cohorts, who also have higher levels of illegal drug use and extensions in the period of risk for initiation.

The Meaning of Cognitive Impairment in the Elderly

In order to determine the meaning of cognitive impairment in community dwelling elderly, 3,481 adults were interviewed in their homes using the Mini‐Mental State Examination. Ninety‐six per cent of the population aged 18–64 scored 23 or higher, whereas 80 per cent of the population 65 and over scored 23 or higher. Individuals with low scores were suffering from a variety of psychiatric disorders including dementia. Thirty‐three per cent of the elderly population scoring in the range of 0–23 had no diagnosable DSM‐III condition. Prevalence of dementia from all causes was 6.1 per cent of the population over age 65. Two per cent of the population over age 65 were diagnosed as having Alzheimers disease

From First Drug Use to Drug Dependence: Developmental Periods of Risk for Dependence upon Marijuana, Cocaine, and Alcohol

The focal point of this paper is the transition from drug use to drug dependence. We present new evidence on risk for starting to use marijuana, cocaine, and alcohol, as well as risks for progression from first drug use to the onset of drug dependence, separately for each of these drugs. Data from the National Comorbidity Survey (NCS) were analyzed. The NCS had a representative sample of the United States population ages 15–54 years (n = 8,098). Survival analysis techniques were used to provide age- and time-specific risk estimates of initiating use of marijuana, cocaine, and alcohol, as well as of becoming dependent on each drug. With respect to risk of initiating use, estimated peak values for alcohol and marijuana were found at age 18, about two years earlier than the later peak in risk of initiating cocaine use. With respect to risk of meeting criteria for the clinical dependence syndrome, estimated peak values for alcohol and marijuana were found at age 17–18. Peak values for cocaine dependence were found at age 23–25. Once use began, cocaine dependence emerged early and more explosively, with an estimated 5–6% of cocaine users becoming cocaine dependent in the first year of use. Most of the observed cases of cocaine dependence met criteria for dependence within three years after initial cocaine use. Whereas some 15–16% of cocaine users had developed cocaine dependence within 10 years of first cocaine use, the corresponding values were about 8% for marijuana users, and 12–13% for alcohol users. The most novel findings of this study document a noteworthy risk for quickly developing cocaine dependence after initial cocaine use, with about one in 16 to 20 cocaine users becoming dependent within the first year of cocaine use. For marijuana and alcohol, there is a more insidious onset of the drug dependence syndrome.

A case‐control study of Alzheimer's disease in Australia

We conducted a case-control study of clinically diagnosed Alzheimers disease (AD) on 170 cases aged 52 to 96 years, and 170 controls matched for age, sex and, where possible, the general practice of origin. Trained lay interviewers naive to the hypotheses and to the clinical status of the elderly person carried out risk-factor interviews with informants. Significant odds ratios were found for 4 variables: a history of either dementia, probable AD, or Downs syndrome in a 1st-degree relative, and underactivity as a behavioral trait in both the recent and more distant past. Previously reported or suggested associations not confirmed by this study include head injury, starvation, thyroid disease, analgesic abuse, antacid use (aluminum exposure), alcohol abuse, smoking, and being left-handed.

APOE-ε4 count predicts age when prevalence of AD increases, then declines The Cache County Study

Objective: To examine the prevalence of Alzheimer’s disease (AD) and other dementias in relation to age, education, sex, and genotype at APOE. Recent studies suggest age heterogeneity in the risk of AD associated with the APOE genotype and a possible interaction between APOE-ε4 and female sex as risk factors. We studied these topics in the 5,677 elderly residents of Cache County, Utah, a population known for long life expectancy and high participation rates. Methods: We screened for dementia with a brief cognitive test and structured telephone Dementia Questionnaire, then examined all individuals with apparent cognitive symptoms and a sample of others. We estimated age-specific prevalence of AD and other dementias and used multiple logistic regression models to describe relation of AD prevalence to age, sex, education, and APOE genotype. Results: We found 335 demented individuals, 230 (69%) with definite, probable, or possible AD (positive predictive value versus autopsy confirmation 85%). The adjusted prevalence estimate for AD was 6.5% and for all dementias 9.6%. After age 90, the adjusted prevalence estimate for AD was 28% and for all dementias 38%. Regression models showed strong variation in AD prevalence with age, sex, education, and number of ε4 alleles (effect of ε2 not significant). Models were improved by a term for age-squared (negative coefficient) and by separate terms for interaction of age with presence of one or two ε4 alleles. An association of AD with female sex was ascribable entirely to individuals with ε4. Conclusions: In participants with no ε4 alleles, the age-specific prevalence of AD reached a maximum and then declined after age 95. In ε4 heterozygotes a similar maximum was noted earlier at age 87, in homozygotes at age 73. Female sex was a risk factor for AD only in those with ε4. The ε4 allele accounted for 70% of the population attributable risk for AD.

Propensity score techniques and the assessment of measured covariate balance to test causal associations in psychological research

There is considerable interest in using propensity score (PS) statistical techniques to address questions of causal inference in psychological research. Many PS techniques exist, yet few guidelines are available to aid applied researchers in their understanding, use, and evaluation. In this study, the authors give an overview of available techniques for PS estimation and PS application. They also provide a way to help compare PS techniques, using the resulting measured covariate balance as the criterion for selecting between techniques. The empirical example for this study involves the potential causal relationship linking early-onset cannabis problems and subsequent negative mental health outcomes and uses data from a prospective cohort study. PS techniques are described and evaluated on the basis of their ability to balance the distributions of measured potentially confounding covariates for individuals with and without early-onset cannabis problems. This article identifies the PS techniques that yield good statistical balance of the chosen measured covariates within the context of this particular research question and cohort.

The incidence of specific DIS/DSM-III mental disorders: data from the NIMH Epidemiologic Catchment Area Program

ABSTRACT Incidence data are presented for the 7 most frequent specific categories of mental disorder available in the NIMH Epidemiologic Catchment Area (ECA) program (major depressive disorder; panic disorder; phobic disorder; obsessive‐compulsive disorder; drug abuse/dependence; alcohol abuse/dependence; cognitive impairment). The DSM‐III case definitions in the ECA Program are according to the implementation of the Diagnostic Interview Schedule (DIS). Rates of incidence are presented specific for age, sex, and site, and pooled smoothed curves for the relationship of age to incidence, specific for sex are shown. The 7 disorders have distinctly different relationships to sex and age of onset.

Reduced incidence of AD with NSAID but not H2 receptor antagonists: The Cache County Study

Background Previous analyses from the Cache County (UT) Study showed inverse associations between the prevalence of AD and the use of nonsteroidal anti-inflammatory drugs (NSAID), aspirin compounds, or histamine H2 receptor antagonists (H2RA). The authors re-examined these associations using data on incident AD. Methods In 1995 to 1996, elderly (aged 65+) county residents were assessed for dementia, with current and former use of NSAID, aspirin, and H2RA as well as three other “control” medication classes also noted. Three years later, interval medication histories were obtained and 104 participants with incident AD were identified among 3,227 living participants. Discrete time survival analyses estimated the risk of incident AD in relation to medication use. ResultsAD incidence was marginally reduced in those reporting NSAID use at any time. Increased duration of use was associated with greater risk reduction, and the estimated hazard ratio was 0.45 with ≥2 years of exposure. Users of NSAID at baseline showed little reduction in AD incidence, regardless of use thereafter. By contrast, former NSAID users showed substantially reduced incidence (estimated hazard ratio = 0.42), with a trend toward greatest risk reduction among those with extended exposure. Similar patterns appeared with aspirin but not with any other medicines examined. Conclusions Long-term NSAID use may reduce the risk of AD, provided such use occurs well before the onset of dementia. More recent exposure seems to offer little protection. Recently initiated randomized trials of NSAID for primary prevention of AD are therefore unlikely to show effects with treatment until participants have been followed for several years.

Tobacco smoking and depressed mood in late childhood and early adolescence.

OBJECTIVES This study builds on previous observations about a suspected causal association linking tobacco smoking with depression. With prospective data, the study sheds new light on the temporal sequencing of tobacco smoking and depressed mood in late childhood and early adolescence. METHODS The epidemiologic sample that was studied consisted of 1731 youths (aged 8-9 to 13-14 years) attending public schools in a mid-Atlantic metropolitan area, who were assessed at least twice from 1989 to 1994. A survival analysis was used to examine the temporal relationship from antecedent tobacco smoking to subsequent onset of depressed mood, as well as from antecedent depressed mood to subsequent initiation of tobacco use. RESULTS Tobacco smoking signaled a modestly increased risk for the subsequent onset of depressed mood, but antecedent depressed mood was not associated with a later risk of starting to smoke tobacco cigarettes. CONCLUSIONS This evidence is consistent with a possible causal link from tobacco smoking to later depressed mood in late childhood and early adolescence, but not vice versa.