Gladys E. Maestre

Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors

Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (>or=5%) in certain Asian and Latin American countries, but consistently low (1-3%) in India and sub-Saharan Africa; Alzheimers disease accounts for 60% whereas vascular dementia accounts for approximately 30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE epsilon4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US

A reliable index for the prognostic significance of blood pressure variability.

73 billion yearly, but care demands social protection, which seems scarce in these regions.

Prevalence of dementia in Latin America: a collaborative study of population-based cohorts

Objectives This study presents a reliable index inspired by the total variability concept of real analysis in mathematics, called average real variability (ARV), for the prognostic significance of blood pressure variability (BPV) overcoming the pitfalls of the commonly used standard deviation (SD). Background Recent studies have suggested that an increase in BPV is associated with an increase in subsequent cardiovascular events/complications. However, there are other studies where the cited association was not found or was lost in the presence of other well-known risk factors. An explanation for these apparently contradictory results may be the selection of the variability index used (SD). Methods Ambulatory blood pressure monitoring in 312 subjects aged ≥ 55 years. Logistic regression models and survival methods were used to establish the prognostic significance of awake systolic BPV: in particular, (i) the performance of ARV versus SD, and (ii) the value of BPV relative to other well-known risk factors. Results The analyses using the ARV index show a statistically significant relative risk equal to 4.548 (P = 0.006) for the group with high BPV with respect to the low BPV group (reference level); in contrast, the corresponding relative risk associated to the SD index was not statistically significant. Furthermore, ARV exhibited a similar predictive value to systolic blood pressure. Conclusions The proposed ARV index is a more reliable representation of time series variability than SD and may be less sensitive to the relative low sampling frequency of the ambulatory blood pressure monitoring devices. The results suggest that ARV adds prognostic value to the ABPM and could prompt the use of therapeutic measures to control BPV.

Effect of Age, Ethnicity, and Head Injury on the Association between APOE Genotypes and Alzheimer's Disease

BACKGROUND Dementia is becoming a major public health problem in Latin America (LA), yet epidemiological information on dementia remains scarce in this region. This study analyzes data from epidemiological studies on the prevalence of dementia in LA and compares the prevalence of dementia and its causes across countries in LA and attempts to clarify differences from those of developed regions of the world. METHODS A database search for population studies on rates of dementia in LA was performed. Abstracts were also included in the search. Authors of the publications were invited to participate in this collaborative study by sharing missing or more recent data analysis with the group. RESULTS Eight studies from six countries were included. The global prevalence of dementia in the elderly (> or =65 years) was 7.1% (95% CI: 6.8-7.4), mirroring the rates of developed countries. However, prevalence in relatively young subjects (65-69 years) was higher in LA studies The rate of illiteracy among the elderly was 9.3% and the prevalence of dementia in illiterates was two times higher than in literates. Alzheimers disease was the most common cause of dementia. CONCLUSIONS Compared with studies from developed countries, the global prevalence of dementia in LA proved similar, although a higher prevalence of dementia in relatively young subjects was evidenced, which may be related to the association between low educational level and lower cognitive reserve, causing earlier emergence of clinical signs of dementia in the LA elderly population.

Ambulatory Blood Pressure Monitoring in 9357 Subjects From 11 Populations Highlights Missed Opportunities for Cardiovascular Prevention in Women

The association between apolipoprotein E (APOE)-epsilon 4 and Alzheimers disease has been confirmed worldwide. We and others have observed a diminished association in the very old and among African-Americans compared to Caucasians and Hispanics in New York. In this review we describe a new method we developed to compare relative risks by APOE genotypes in an expanded cohort of cases and controls from three ethnic groups in a New York City community and discuss the association as between APOE epsilon 4 and Alzheimers disease as modified by head injury. Compared to persons with APOE epsilon 3/epsilon 3 genotypes, relative risk (RR) for Alzheimers disease associated with APOE epsilon 4 homozygosity was similar across ethnic groups (African-American RR = 3.3; 95% c.i. 1.6-6.8; Caucasian RR = 5.3; 1.6-16.0; Hispanic RR = 2.5; 1.1-5.8). The risk was also increased for APOE epsilon 4 heterozygous Caucasians (RR = 3.2; 1.8-5.8) and Hispanics (RR 1.5; 1.0-2.2) but not African-Americans (RR = 0.6; 0.4-0.9). Risk of AD was not significantly diminished for individuals in any group with APOE epsilon 2/epsilon 2 or -epsilon 2/epsilon 3 genotypes. A 10-fold increase in the risk of Alzheimers disease was associated with both APOE epsilon 4 and a history of traumatic head injury, compared to a twofold increase in risk with APOE epsilon 4 alone. Head injury in the absence of an APOE epsilon 4 allele did not increase risk. These results imply that in Alzheimers disease genotypic risk associated with APOE may be influenced by age, ethnicity, and certain environmental factors.

Setting thresholds to varying blood pressure monitoring intervals differentially affects risk estimates associated with white-coat and masked hypertension in the population

To analyze sex-specific relative and absolute risks associated with blood pressure (BP), we performed conventional and 24-hour ambulatory BP measurements in 9357 subjects (mean age, 52.8 years; 47% women) recruited from 11 populations. We computed standardized multivariable-adjusted hazard ratios for associations between outcome and systolic BP. During a course of 11.2 years (median), 1245 participants died, 472 of cardiovascular causes. The number of fatal combined with nonfatal events was 1080, 525, and 458 for cardiovascular and cardiac events and for stroke, respectively. In women and men alike, systolic BP predicted outcome, irrespective of the type of BP measurement. Women compared with men were at lower risk (hazard ratios for death and all cardiovascular events=0.66 and 0.62, respectively; P<0.001). However, the relation of all cardiovascular events with 24-hour BP (P=0.020) and the relations of total mortality (P=0.023) and all cardiovascular (P=0.0013), cerebrovascular (P=0.045), and cardiac (P=0.034) events with nighttime BP were steeper in women than in men. Consequently, per a 1-SD decrease, the proportion of potentially preventable events was higher in women than in men for all cardiovascular events (35.9% vs 24.2%) in relation to 24-hour systolic BP (1-SD, 13.4 mm Hg) and for all-cause mortality (23.1% vs 12.3%) and cardiovascular (35.1% vs 19.4%), cerebrovascular (38.3% vs 25.9%), and cardiac (31.0% vs 16.0%) events in relation to systolic nighttime BP (1-SD, 14.1 mm Hg). In conclusion, although absolute risks associated with systolic BP were lower in women than men, our results reveal a vast and largely unused potential for cardiovascular prevention by BP-lowering treatment in women.

Age-specific differences between conventional and ambulatory daytime blood pressure values.

Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using ≥140/≥90, ≥130/≥80, ≥135/≥85, and ≥120/≥70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion, identification of truly low-risk white-coat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice.

Modulation by age and gender of risk for Alzheimer's disease and vascular dementia associated with the apolipoprotein E-ε4 allele in Latin Americans: Findings from the Maracaibo Aging Study

Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals <50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P<0.0001). In individuals aged 60 to 70 and ≥70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P<0.0001).The prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18 to 30 years to those aged ≥70 years, with little variation between men and women (8.0% versus 6.1%; P=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%; P<0.0001). The age-specific prevalences of masked hypertension were 18.2%, 27.3%, 27.8%, 20.1%, 13.6%, and 10.2% among men and 9.0%, 9.9%, 12.2%, 11.9%, 14.7%, and 12.1% among women. In conclusion, this large collaborative analysis showed that the relation between daytime ambulatory and conventional BP strongly varies by age. These findings may have implications for diagnosing hypertension and its subtypes in clinical practice.

High prevalence of dementia in a Caribbean population.

An ongoing longitudinal study in Maracaibo, Venezuela, examined the interaction between apolipoprotein E (APOE) genotypes and Alzheimers disease (AD) and vascular dementia (VD), evaluating age and gender as potential modifiers of risk. Overall, carriers of at least one epsilon4 allele were at higher risk for AD, not for VD; however, the risk was significant only for subjects older than 65, and it increased 10-fold in subjects older than 85. The risk of AD conferred by APOE-epsilon4, adjusted for age and stratified by gender, was significant only for women. No association was found between the epsilon-2 allele and AD or VD. The results support the notions that APOE-epsilon4 is relevant for late-onset, not early onset AD, and that age and gender act as modulators of this association.

The Maracaibo Aging Study: Population and Methodological Issues

Background/Aims: People in Caribbean countries are thought to be at particularly high risk for dementia. Basic descriptive epidemiology of dementia is required for populations in the region to determine the validity of this hypothesis. The main objectives of the study were to assess the prevalence, types and severity of dementia among elderly people (≥55 years old) in an urban area on the Caribbean coast of Venezuela, and to determine the gender and age distribution of affected people. Methods: The population-based Maracaibo Aging Study included 3,657 subjects, all of whom underwent a standardized, in-person interview. 2,438 of these subjects underwent neuropsychological, neuropsychiatric, cardiovascular and nutritional assessment. Results: The overall prevalence rate of dementia in elderly subjects was 8.04% and was not significantly different for women and men. Alzheimer’s disease was the most frequent type of dementia (50%), followed by vascular dementia (27%). Of all cases of dementia, 41.84% were ranked as mild, 30.10% as moderate and 28.06% as severe. Conclusion: The prevalence of dementia in elderly people from the Caribbean coast of Venezuela is much higher than frequencies previously reported for developing countries.