Alzheimer\'s Disease Course Project Part

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.

Causality Criteria

Description: An assessment of genetic and environmental risk factors and prevalence, and incidence of dementia of the Alzheimer type (DAT) among the elderly in an Arab community in Israel.

Exposure, Intervention: All persons aged 60 years or older who were residents of the rural area of Wadi Ara were examined for identification of dementia associated with Alzheimer's disease (DAT), vascular dementia (VaD) and age related cognitive decline (ARCD) due to AD. DSM-IV criteria and a semi-structured questionnaire were used. "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)."