Association Between Anticholinergic Drugs and Apolipoprotein E ɛ4 Allele and Poorer Cognitive Function in Older Cardiovascular Patients: A Cross-Sectional Study

OBJECTIVES: To clarify the association between anticholinergic drugs and apolipoprotein E ɛ4 allele carrier status ( APOE4 ) and cognitive dysfunction.
DESIGN: Cross-sectional analyses of current drug use and cognitive functioning according to the baseline assessments of the Drugs and Evidence-Based Medicine in the Elderly Study.
SETTING: Helsinki, Finland.
PARTICIPANTS: Four hundred community-dwelling people aged 75 to 90 without clinical dementia but with a history of stable atherosclerotic disease.
MEASUREMENTS: Cognitive function according to the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Scale (CDR). Participants' use of anticholinergic drugs was estimated using definitions from previous scientific literature. APOE alleles determined from peripheral blood leukocyte deoxyribonucleic acid using standard polymerase chain reaction–based methods.
RESULTS: There was an association between anticholinergic drugs and lower MMSE scores ( P for trend <.001). The higher the number of anticholinergic drugs, the lower the MMSE score. Subjects with the APOE4 allele and using drugs with anticholinergic properties had the lowest median MMSE score (26), whereas those without the APOE4 allele and not using drugs with anticholinergic properties had the highest median MMSE score (28). When adjusted for age, sex, and education, the difference between the groups remained significant. The finding was similar for CDR scores.
CONCLUSION: Use of drugs with anticholinergic properties was associated with lower cognitive function irrespective of APOE4 carrier status. Having lower cognitive function as a group, APOE4 carriers may be more vulnerable to this undesirable effect, but a follow-up study is needed to demonstrate this.     

Depressive Symptoms and Cognitive Decline in Community‐Dwelling Older Adults

OBJECTIVES: To examine the temporal association between depressive symptoms and cognitive functioning and estimate the effect measure modification of the apolipoprotein E (APOE) ?4 allele on this relationship. DESIGN: Prospective cohort study. SETTING: General community. PARTICIPANTS: Population‐based sample of 598 cognitively intact older adults aged 60 and older, with re‐assessments after 3 (N=479) and 6 years (N=412). MEASUREMENTS: Depressive symptoms (Symptom Checklist) and neurocognitive functioning (memory, Visual Verbal Learning Test; attention, Stroop Color–Word Test; processing speed, Letter Digit Substitution Test; general cognition, Mini‐Mental State Examination). Longitudinal associations were assessed using linear mixed models. The risk for cognitive impairment, no dementia (CIND) was examined using logistic regression. RESULTS: Adjusting for age, sex, education, and baseline cognition, the rate of change in memory z‐scores was 0.00, ?0.11, ?0.20, and ?0.37 for those in the lowest (reference group), second, third, and highest depressive symptom quartiles at baseline, respectively (P<.001 for highest vs lowest quartile). The odds ratios for developing CIND with amnestic features were 1.00, 0.87, 0.69, and 2.98 for the four severity groups (P=.05 for highest vs lowest quartile). Associations were strongest for those with persistent depressive symptoms, defined as high depressive symptoms at baseline and at least one follow‐up visit. Results were similar for processing speed and global cognitive function but were not as strong for attention. No APOE interaction was observed. CONCLUSION: Depression and APOE act independently to increase the risk for cognitive decline and may provide targets for prevention and early treatment.     

White Matter Hyperintensities Predict Functional Decline in Voiding,Mobility, and Cognition in Older Adults

OBJECTIVES: To compare magnetic resonance imaging data with functional assessments of mobility, urinary control, and cognition to determine common or distinctive features in the distribution of brain white matter hyperintensities (WMHs) associated with functional decline and impairment. DESIGN: Baseline data from subjects aged 75 to 89 enrolled in a longitudinal study. Assessors and subjects were blinded to group assignment. SETTING: Healthy community‐dwelling volunteers. PARTICIPANTS: Ninety‐nine subjects were enrolled using a balanced 3 × 3 matrix stratified according to age and mobility performance. Exclusion criteria were medication, systemic conditions, and neurological diseases that can compromise mobility. MEASUREMENTS: WMHs were identified using a semi‐automated segmentation method, and regional burdens were assessed using a white matter parcellation atlas. Quantitative measures of mobility, urinary incontinence (UI) severity, and executive function and processing speed were obtained. RESULTS: WMHs occur predictably in predominantly periventricular areas. There were powerful correlations between total (tWMH) and regional (rWMH) WMH, with correlation coefficients of 0.5 to 0.9 for eight of 10 structures analyzed. tWMH predicted functional measures of UI, mobility, executive function, and processing speed nearly as well as the best regional measures. The total volume of WMHs independently explains 5% to 11% of the variability for mobility, UI severity, executive function, and processing speed and is a sensitive (0.7–0.8) predictor of functional decline. The odds of decline in each of the three functional domains was 1.5 to 2.4 times greater with each 1% increase in tWMH. CONCLUSION: This work establishes the importance of brain WMH burden in three major geriatric syndromes. The findings support the inclusion of total WMH burden as a risk factor in the predictive and diagnostic criteria.