Effects of Vascular Risk Factors on the Association of Blood-Based Biomarkers with Alzheimer's Disease.

Background: Comorbidities may influence the levels of blood-based biomarkers for Alzheimer's disease (AD). We investigated whether differences in risk factors or comorbid conditions might explain the discordance between clinical diagnosis and biomarker classifications in a multi-ethnic cohort of elderly individuals. Aims: To evaluate the relationship of medical conditions and other characteristics, including body mass index (BMI), vascular risk factors, and head injury, with cognitive impairment and blood-based biomarkers of AD, phosphorylated tau (P-tau 181, P-tau 217), in a multi-ethnic cohort. Methods: Three-hundred individuals, aged 65 and older, were selected from a prospective community-based cohort for equal representation among three racial/ethnic groups: non-Hispanic White, Hispanic/Latino and African American/Black. Participants were classified into four groups based on absence (Asym) or presence (Sym) of cognitive impairment and low (NEG) or high (POS) P-tau 217 or P-tau 181 levels, determined previously in the same cohort: (Asym/NEG, Asym/POS, Sym/NEG, Sym/POS). We examined differences in individual characteristics across the four groups. We performed post-hoc analysis examining the differences across biomarker and cognitive status. Results: P-tau 217 or P-tau 181 positive individuals had lower BMI than P-tau negative participants, regardless of symptom status. Symptomatic and asymptomatic participants did not differ in terms of BMI. BMI was not a mediator of the effect of P-tau 217 or P-tau 181 on dementia. Frequencies of other risk factors did not differ between the four groups of individuals. Conclusions: Participants with higher levels of P-tau 217 or P-tau 181 consistent with AD had lower BMI regardless of whether the individual was symptomatic. These findings suggest that weight loss may change with AD biomarker levels before onset of cognitive decline. They do not support BMI as a confounding variable. Further longitudinal studies could explore the relationship of risk factors with clinical diagnoses and biomarkers.

A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families.

CONTEXT: Genetic determinants of Alzheimer disease (AD) have not been comprehensively examined in Caribbean Hispanics, a population in the United States in whom the frequency of AD is higher compared with non-Hispanic whites. OBJECTIVE: To identify variant alleles in genes related to familial early-onset AD among Caribbean Hispanics. DESIGN AND SETTING: Family-based case series conducted in 1998-2001 at an AD research center in New York, NY, and clinics in the Dominican Republic. PATIENTS: Among 206 Caribbean Hispanic families with 2 or more living members with AD who were identified, 19 (9.2%) had at least 1 individual with onset of AD before the age of 55 years. MAIN OUTCOME MEASURE: The entire coding region of the presenilin 1 gene and exons 16 and 17 of the amyloid precursor protein gene were sequenced in probands from the 19 families and their living relatives. RESULTS: A G-to-C nucleotide change resulting in a glycine-alanine amino acid substitution at codon 206 (Gly206Ala) in exon 7 of presenilin 1 was observed in 23 individuals from 8 (42%) of the 19 families. A Caribbean Hispanic individual with the Gly206Ala mutation and early-onset familial disease was also found by sequencing the corresponding genes of 319 unrelated individuals in New York City. The Gly206Ala mutation was not found in public genetic databases but was reported in 5 individuals from 4 Hispanic families with AD referred for genetic testing. None of the members of these families were related to one another, yet all carriers of the Gly206Ala mutation tested shared a variant allele at 2 nearby microsatellite polymorphisms, indicating a common ancestor. No mutations were found in the amyloid precursor protein gene. CONCLUSIONS: The Gly206Ala mutation was found in 8 of 19 unrelated Caribbean Hispanic families with early-onset familial AD. This genetic change may be a prevalent cause of early-onset familial AD in the Caribbean Hispanic population.

Knowledge, beliefs, and barriers relevant to colorectal cancer screening in an urban population: a pilot study.

A sample of 115 urban, working-class, predominantly minority men and women was interviewed by telephone to assess knowledge, beliefs, and barriers relevant to colorectal cancer (CRC) and CRC screening. More than half (53.9%) were unable to name a CRC screening test. Misconceptions were common. Dispelling inaccurate beliefs, establishing an individual's preference for fecal occult blood tests or flexible sigmoidoscopy, and helping individuals take a proactive role in the receipt of CRC screening are important goals for health education efforts aimed at increasing rates of CRC screening. Participants' willingness to engage in detailed telephone conversations about CRC and CRC screening was encouraging.

Preventive services among Medicare beneficiaries with supplemental coverage versus HMO enrollees, medicaid recipients, and elders with no additional coverage.

BACKGROUND: Studies conducted when Medicare began to cover preventive services, found that beneficiaries with supplemental insurance were much more likely to have such services than those without additional coverage. OBJECTIVE: To examine preventive services among Medicare beneficiaries with supplemental insurance, Medicaid, health maintenance organization (HMO) enrollees, and those without additional insurance. RESEARCH DESIGN: Analysis of the 1996 Medical Expenditure Panel Survey, a nationally representative multistage survey. SUBJECTS: 2,251 persons aged 65 and older with Medicare coverage. MEASURES: Self-reported preventive services, specifically, blood pressure measurement, cholesterol testing, influenza vaccination, mammography, Papanicolau (Pap) testing, and breast and prostate examinations. Multivariate modeling was used to adjust for age, education, race/ethnicity, and functional status. RESULTS: Elders without additional coverage were approximately 10% points less likely to have influenza vaccination, cholesterol testing, mammography, or Pap smears than those with supplemental coverage (P < 0.05). Multivariate adjustment attenuated some of these differences with age and education being the most important predictors of having preventive services. HMO enrollees were more likely to have mammograms than those with supplemental coverage (P < 0.05). CONCLUSIONS: Several years after Medicare extended coverage to include preventive services, differences in utilization of such services among elders with and without supplemental insurance have narrowed substantially.

Medically unexplained symptoms in an urban general medicine practice.

The authors investigated the prevalence of multiple medically unexplained symptoms (MMUS) as identified by primary care physicians (PCPs) in a systematic sample of 172 patients. Patients were from a university-affiliated urban primary care practice serving a low-income population. Patients with a history of MMUS were older (mean: 57.2 vs. 53.0 years), more likely to be female (90.5% vs. 72.3%), and less likely to be married or living with a partner (14.4% vs. 36.2%) than those without MMUS. Patients with MMUS had over twice the rate of any current psychiatric disorder, almost two-and-a-half times the rate of any current anxiety disorder, and greater functional impairment. These data suggest that patients with MMUS are as common in urban primary care clinics as in more affluent clinics and reinforce the need for PCPs to screen these patients for common and treatable psychiatric conditions.

Differences in functional status of Hispanic versus non-Hispanic White elders: data from the Medical Expenditure Panel Survey.

OBJECTIVES: Few national studies have focused specifically on the functional status of Hispanic elders. We examined the prevalence of functional limitations and disabilities among Hispanic and Black elders compared to non-Hispanic Whites. METHODS: We analyzed seven measures of functional limitations, disabilities, and dependencies. Logistic regression was used to examine racial and ethnic group differences adjusting for age, gender, and education. RESULTS: Compared to non-Hispanic Whites, Hispanics tended to report greater instrumental activities of daily living (IADL) dependencies and cognitive disabilities. Blacks were more likely to have activities of daily living (ADL) and IADL dependencies and require use of assistive devices compared to non-Hispanic Whites. Further adjustment for respondent status reduced differences between groups, but these models may overadjust for functional status differences. DISCUSSION: Given the projected growth of minority elders, policymakers and planners will need to consider race and ethnic differentials in functional status in determining future medical and social service needs.

Piperidine enhances sleep-related and insulin-induced growth hormone secretion: further evidence for a cholinergic secretory mechanism.

Piperidine, a nicotinic cholinergic receptor stimulator, was used in paired design studies of sleep-related and insulin-induced GH and PRL secretion. For the sleep studies, 100 mg piperidine or an equal volume of saline were infused for 30 min starting at sleep onset in eight normal volunteers. The same dose of piperidine was infused for 30 min (beginning 15 min before insulin injection) in an additional eight volunteers undergoing insulin tolerance tests. After piperidine administration, there was a significant (P less than 0.01) enhancement of sleep-related GH secretion, abut no change in PRL. GH concentrations during the first 2 h of sleep were 7.2 +/- 1.2 ng/ml after saline and 15.2 +/-2.9 ng/ml after piperidine (P less than 0.01). No alteration in any measured sleep parameter was noted with the drug. Piperidine did not affect the daytime insulin-induced secretion of either GH or PRL, as assessed by an analysis of variance. However, paired analysis of increments and areas under the response curves indicated a statistically significant effect for GH but not PRL. The maximum GH increment with piperidine was 48.0 +/- 4.3 ng/ml, compared to 36.8 +/- 3.6 ng/ml with saline (P less than 0.01). Piperidine given alone did not influence daytime concentrations of GH. These data are consistent with the view proposed by us, on the bass of methoscopolamine inhibition of nocturnal GH secretion, that cholinergic pathways play a facilitatory role in sleep-related and insulin-induced GH secretion. Thus, cholinergic mechanisms stimulate GH secretion. Nicotinic as well as muscarinic pathways appear to be involved, although the quantitative nicotinic contribution seems to be smaller than the associated with muscarinic sites.