Neuropsychological performance in advanced age: Influences of Demographic factors and Apolipoprotein E: Findings from the Cache County Memory Study

Abstract

The Cache County Study of Memory in Aging (CCMS) is an epidemiological study of Alzheimer's disease (AD), mild cognitive disorders, and aging in a population of exceptionally long-lived individuals (7th to 11th decade). Observation of population members without dementia provides an opportunity for establishing the range of normal neurocognitive performance in a representative sample of the very old. We examined neurocognitive performance of the normal participants undergoing full clinical evaluations (n = 507) and we tested the potential modifying effects of apolipoprotein E (APOE) genotype, a known genetic risk factor for the later development of AD. The results indicate that advanced age and low education are related to lower test scores across nearly all of the neurocognitive measures. Gender and APOE ϵ 4 both had negligible and inconsistent influences, affecting only isolated measures of memory and expressive speech (in case of gender). The gender and APOE effects disappeared once age and education were controlled. The study of this exceptionally long-lived population provides useful normative information regarding the broad range of “normal” cognition seen in advanced age. Among elderly without dementia or other cognitive impairment, APOE does not appear to exert any major effects on cognition once other demographic influences are controlled.

Keywords:

• Normative studies
• Aging
• Apolipoprotein E
• Alzheimer's disease

Acknowledgments

We wish to thank Brenda Plassman, Ph.D. for her thoughtful review of this manuscript. We are grateful to the neurogenetics laboratory of the Bryan Alzheimer's Disease Research Center at Duke University for the APOE genotyping, and to Cara Brewer, B.A., Tony Calvert, B.Sc., Michelle McCart, B.A., Tiffany Newman, B.A., Roxane Pfister, M.A., Nancy Sassano, Ph.D., Sarah Schwartz, M.S., and Joslin Werstack, B.A. for expert technical assistance.

The other Cache County Study of Memory, Health, and Aging Investigators involved in this work include: James Anthony, Ph.D., Erin Bigler, Ph.D., John Breitner, M.D., M.Ph., Ron Brookmeyer, Ph.D., James Burke, M.D., M.Ph., Eric Christopher, M.D., Chris Corcoran, Sc.D., Jane Gagliardi, M.D., Robert Green, M.D., Michael Helms, Christine Hulette, M.D., Ara S. Khatchaturian, Ph.D., Liz Klein, M.Ph., Carol Leslie, M.S., Constantine Lyketsos, M.D., M.H.S., Lawrence Mayer, M.D., John Morris, M.D., Ron Munger, Ph.D., M.Ph., Chiadi Onyike, M.D., M.H.S., Ron Petersen, M.D., Kathy Piercy, Ph.D., Brenda Plassman, Ph.D., Peter Rabins, M.D., Pritham Raj, M.D., Russell Ray, M.S., Ingmar Skoog, M.D., David Steffens, M.D., M.H.S., Martin Steinberg, M.D., Marty Toohill, Ph.D., Leslie Toone, M.S., Jeannette Townsend, M.D., Lauren Warren, M.A., Heidi Wengreen, Ph.D., Michael Williams, M.D., Bonita Wyse, Ph.D., and Peter Zandi, Ph.D.

Dr Welsh-Bohmer and Dr Breitner designed the neuropsychological and clinical assessment procedures for this study. Dr Tschanz provided training and oversight of all field staff and reviewed all individual neuropsychological test results to render professional diagnoses. The board-certified or board-eligible geriatric psychiatrists or neurologists who examined the study members included in these analyses of our Wave 1 and Wave 2 data include Drs Steinberg, Breitner, Steffens, Lyketsos, and Green. Dr Williams also examined several participants and provided expert neurologic consultation. Autopsy examinations were conducted by Dr Townsend. Ms. Leslie coordinated the autopsy enrollment program. Diagnosticians at the expert consensus conferences included Drs Breitner, Burke, Lyketsos, Plassman, Steffens, Steinberg, Toohill, Tschanz, and Welsh-Bohmer.

The Cache County Study on Memory, Health and Aging is supported by the National Institutes of Aging grant: AG R01-11380.