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To appreciate how cognition changes with normal aging requires an understanding of some of the limitations that are inherent in studying cognition and aging.3 4 5 Studies of cognition across the life span are subject to several biases, some of which apply in general and some that are specific to study design. General biases include recruitment bias and misclassification bias. Recruiting subjects for any clinical research study may be biased by which subjects are willing to enroll (recruitment bias). For example, those who are too ill or have more limited social and financial support may find it hard to participate. Recruitment bias tends to underestimate the degree of cognitive decline seen with aging because only the healthiest or most advantaged are included in the study. Misclassification bias is when a subject is misclassified in a research study, such as classifying a subject as normal when they are not. For example, by misclassifying a subject as normal when they actually have early signs and symptoms of a degenerative dementia, this subject's cognitive test scores would overestimate the degree of cognitive decline attributed to normal aging and add a misclassification bias to the study.

Study design biases include cohort bias, practice effect (learning) bias, and attrition (survival) bias. Cohort bias occurs in cross-sectional study designs that compare groups of subjects (cohorts) in specific age groups on their performance on cognitive tests. The cohort bias is the difference between groups that is not due to aging but is due to other differences, often unmeasured, between the age cohorts. For example, when comparing a cohort of subjects that were born in the 1990s to subjects born in the 1940s, the two cohorts might differ significantly in nutritional variables, childhood educational experiences, exposure to environmental toxins or social stressors, knowledge of new technology, and other unmeasured variables. These other factors may influence test performance over and above normal cognitive aging. Longitudinal studies examine how an individual person performs on cognitive tests over time to understand how aging affects cognition. One limitation of longitudinal studies is the practice effect (or learning) bias. By testing subjects on similar test batteries over time, there is the potential for improvement in test performance due to a practice effect. A second bias found in longitudinal studies is attrition or survival bias. If there is selective attrition of subjects over time, the remaining subjects' results may not be generalizable to other older adults. For example, if a subgroup of patients selectively remains in the study (e.g., the healthiest or the best educated), their change in cognition may not accurately reflect the change in cognition with normal aging for many older adults. Both learning bias and attrition bias tend to underestimate the degree of cognitive decline seen with age.

Despite these limitations in studying normal cognitive aging, there is research evidence of predictable and reproducible changes in cognition that occur with normal aging.3 4 6 7 The most common terminology, used to describe which cognitive abilities change with age and which do not, divides cognitive abilities into crystallized abilities and fluid abilities. Crystallized abilities are the cumulative skills and memories that result from cognitive processing that occurred in the past, typically in the form of acquired knowledge. Tests of general knowledge (e.g., reading comprehension, math, science), historical information, and vocabulary would reflect crystallized abilities. Fluid abilities require cognitive processing at the time of assessment and reflect manipulation and transformation of information to complete the test. Tests of fluid abilities require the subject to attend to one's environment and process new information quickly to solve problems. Multiple cross-sectional studies have shown that there is an improvement in crystallized abilities until approximately age 60 followed by a plateau until age 80, and there is steady decline in fluid abilities from age 20 to age 80 (see Fig. 1). For example, there is a nearly linear decline in processing speed, a fluid ability, with a −0.02 standard deviation decline per year in one very large study.4