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Principal Investigator  
Principal Investigator's Name: Anh Khoa Vo
Institution: University of British Columbia
Department: Pharmaceutical Sciences
Proposed Analysis: Association between Anticholinergic Medication Use and Cerebrospinal Fluid beta-amyloid ratio and plasma tau levels Importance: There is strong evidence for a link between cognitive impairment and increased risk of dementia with anticholinergic medication use. Although other studies have shown an association between use of anticholinergic medications and cognition, brain metabolism and brain atrophy using imaging biomarkers, the aim of this study is to look at the association between anticholinergic medication use and biospecimen biomarkers including cerebrospinal fluid (CSF) beta amyloid, plasma Ab42/Ab40 ratio, and plasma tau levels. Central Question: Is the use of anticholinergic medications associated with higher level of CSF beta-amyloid, plasma Ab42/Ab40 ratio and plasma tau levels. Outcome Measures: - Levels of CSF beta-amyloid, plasma Ab42/Ab40 ratio, plasma tau level - AC medication use and association with clinical progression from “normal” to MCI and or AD (co-varied for age, sex, and medical history variables, and AB positivity). Hypothesis: We hypothesize that use of anticholinergic medications will be associated with a higher level of CSF beta-amyloid, plasma Ab42/Ab40 ratio and plasma tau levels. Method: Alzheimer Disease Neuroimaging Initiative (ADNI) - Data will be obtained from the ADNI database. Anticholinergic Medications: - Medication records from the ADNI database will be used to identify medications with low, medium or high AC effects as defined by the anticholinergic cognitive burden (ACB) scale. The total AC burden score will be calculated using the ACB scale (low effect=1, medium effect=2, high effect=3) - AC positive participants will be defined as those taking the medication at baseline visit for a minimum of 1 month - Participants will be divided as: o 1 or more of such medications with medium or high AC activity (AC+) o Those not taking any such medications (AC-) Cognitive Testing: - The ADNI participants all have comprehensive cognitive and clinical batteries. - Measures that will be looked at: o Executive Function (Trail Making Test Part B (TMT-B), a composite executive function score) o Memory using the Weschler Memory Scale revised Logical Memory immediate and Delayed, a composite memory score Confounding Effects of Medical History and Medication Use (Data to control for) - Evaluation of the effect of the total number of medications - Total number of common co-morbid conditions and individual ones (transient ischemic attack, myocardial infarction, cardiac surgery, hypertension, hyperlipidemia, diabetes, sleep apnea, other vascular disorders, insomnia, depression, anxiety, attention-deficit/hyperactivity disorder, and other psychiatric disorder) - Presence or absence of each comorbid condition - Years of Education
Additional Investigators