Epidemiological studies of Alzheimer's disease risk factors and manifestations

Alzheimer's Disease

Course project part II: Reading and reviewing current epidemiological studies

I selected a variety of studies from international peer-reviewed publications, focusing first on the manifestation of Alzheimer's disease; the second two on causal factors associated with AD in specific genetic populations.

The first article studied behavioral risk factors, the second genetic risk factors, the third genetic and environmental risk factors.

The determinants of the first study were to examine the phenomenon of the expression of the disease itself, the determinants of the other two were to determine the interplay between various risk factors, including genetic predispositions, heart disease, and educational levels (in the case of the third study).

Study

Satler, Corina; Carlos Uribe, Carlos Conde, Sergio Leme Da-Silva, & Carlos Tomaz. (2010).

Emotion processing for arousal and neutral content in Alzheimer's disease.

International Journal of Alzheimer Disease. Retrieved October 10, 2011 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2915644/

Causality Criteria

Description: An assessment of the ability of Alzheimer's disease (AD) patients to perceive and process emotional information

Exposure, Intervention: Subjects watched a neutral and emotional story, asked to interpret both

Outcome: As well as memory, emotional interpretation was also impacted by AD

Study design: Experimental; correlative

Study Population: 24 subjects (12 with Alzheimer's Disease, 12 in a control group without AD)

Main Result: Emotional processing is part of the decline associated with AD

Internal Validity

Observation bias: Questionnaires, rather than interviews used to measure validity

Recall bias: Use of Emotional Memory Test, a previously well-tested screening instrument was designed to reduce bias

Confounding: Demographic characteristics were assessed by a t-test; emotional rating scores and total answers for each version of the test were evaluated by a mixed-model ANOVA 2 x 2; Stepwise linear regression analyses were performed for each group to determine the best predictors of dependent variables

Chance: Possible, given the small sample size

Generalizability

Eligible population: Patients with AD

Source population: Yes, can be applied to the source AD population

Other population: Other sources of cognitive decline could reduce emotional recall, but that cannot be determined from this study

Study 2:

Chacon, Aldrin E. Molero; Gloria Pino-Ramirez; Jose A. Luchsinger; Joseph H. Lee; & Gladys

E. Maestre. (2010). Risk of dementia associated with elevated plasma homocysteine in a Latin American population. International Journal of Alzheimer Disease. Retrieved October 10, 2011 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925085/

Causality Criteria

Description: An assessment of the relationship between total homocysteine (tHcy) and dementia risk

Exposure, Intervention: Plasma tHcy, vitamin B12, and folate were measured using blood samples obtained between 7: 00 and 8:00 AM, after overnight fasting to determine plasma levels. Diagnosis of AD was performed according to standard DSM criteria; diagnosis of stroke was self-reported.

Study design: Correlative

Study Population: 2100 Venezuelans (?55 years old) of the Maracaibo Aging Study, designed to study patients with a high genetic risk for developing AD

Main Result: Elevated levels associated with dementia, even when other risk factors taken into account

Internal Validity

Observation bias: Possible observational bias in self-reporting of strokes

Recall bias: Population had already been pre-screened for presence of AD

Confounding: "Means for demographic characteristics were compared using t-tests, and differences in the distribution of cardiovascular risk factors between groups (e.g., demented vs. nondemented) were evaluated using the Pearson ?2 test. Levels of tHcy, vitamin B12, and folate were log-transformed to fit normal distributions. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated using two logistic regression models."

Chance: Low, given the long-term screening of subjects for AD in larger Maracaibo Aging Study

Generalizability

Eligible population: Patients with a strong genetic predisposition for AD

Source population: Uncertain, given the diverse range of factors that could still affect the health of the source population, although many common risk factors were accounted for in the statistical analyses performed

Other population: Generalizability between the Maracaibo population and the AD population as a whole is still being determined.

Study 3:

Bowirrat A; R.P. Friedland; L. Farrer, C. Baldwin, A. Korczyn. (2002). Genetic and environmental risk factors for Alzheimer's disease in Israeli Arabs.

Journal of Molecular Neuroscience, 19(1-2):239-45.

Study Population: Residents of remote Arab village

Main Result: DAT (dementia of the Alzheimer's type) was diagnosed in 20.5% of this population. Illiteracy, old age, and female strongly correlated with development of AD. "The ApoE epsilon4 allele is relatively uncommon in this population and it cannot explain the high DAT prevalence." But it was similarly found that vascular-related dementia and age related-dementia were also correlated.

Internal Validity

Observation bias: Possible observational bias given open-ended nature of questionnaires and difficulty of determining cause of dementia

Recall bias: Questionnaires described as semi-structured, leading to possible bias

Confounding: "ApoE genotype was also determined. Total plasma homocysteine (tHcy) was determined using HPLC with fluorescence detection. Vitamins B12 and plasma folate were determined using a commercial radioisotope dilution kit assay (ICN)."

Chance: High, given singularity of test population.

Generalizability

Eligible population: All residents of remote Israeli Arab village

Source population: Uncertain, particularly given the subjective nature of the causality of the different dementias studied

Other population: Points to need for further examination of relationship of illiteracy to dementia of different kinds