Measurements of cognitive status.

Each participant completed an in-person evaluation including 3 components: 1) interview by a nurse or study coordinator to collect medical and neurologic history, to assess functional abilities, and to document risk factors; 2) a neurologic evaluation; and 3) neuropsychological testing. The interview included a short set of questions about memory administered directly to the participant, and the Clinical Dementia Rating Scale (CDR)¹⁰ and the Functional Activities Questionnaire (FAQ)¹¹ administered to the informant. The neurologic evaluation was performed by a physician and included administration of the Short Test of Mental Status (STMS),¹² medical history review, and a complete neurologic examination.

Neuropsychological testing was performed using 9 cognitive tests to assess 4 cognitive domains: memory (Logical Memory-II [delayed percent retention] and Visual Reproduction-II [delayed percent retention] from Wechsler Memory Scale-Revised and delayed percent retention from the Auditory Verbal Learning Test¹³); executive function (Trail Making Test B and Digit Symbol Substitution from Wechsler Adult Intelligence Scale-Revised [WAIS-R]); language (Boston Naming Test and category fluency); and visuospatial skills (Picture Completion and Block Design from the WAIS-R). We transformed the raw scores on each test into age-adjusted scores using normative data from the Mayo's Older American Normative Studies. These adjusted scores were scaled to have a mean of 10 and a SD of 3.¹³ We then obtained domain scores by summing the adjusted and scaled scores of the tests included within each domain. The domain scores were also scaled to allow comparisons across domains.

Subjects who refused the in-person evaluation but accepted a telephone interview were administered a structured questionnaire including the Telephone Interview for Cognitive Status-modified (TICS-m).¹⁴ However, because the TICS-m was found to perform only fairly well in separating MCI from either normal cognition or dementia, we excluded from this study the 669 subjects who only accepted a telephone interview.¹⁵

Demographic and clinical factors.

Date of birth, number of years of education, marital status, prior occupation, and history of diabetes, hypertension, coronary heart disease, and depression were obtained from the nurse interview and risk factors assessment, and a history of stroke and of other conditions possibly related to cognitive performance was obtained by the physician. Whenever possible, these comorbidities were confirmed with information from the medical records-linkage system.^8,16

Diagnostic categories.

The performance of a person in a particular cognitive domain was measured by comparing the person's domain score with the score in normal subjects, available from normative work conducted in this same population.^13,17 Subjects with scores of 1.0 SD or greater below the age-specific mean in the general population were considered for a possible cognitive impairment. However, the final decision about impairment in any cognitive domain was not based on a simple computer algorithm but rather on a consensus agreement among the examining physician, nurse, and neuropsychologist taking into account education, prior occupation, visual or hearing deficits, and other information.⁸

MCI was defined according to the following published criteria: 1) cognitive concern by subject, informant (from CDR), or nurse or physician; 2) impairment in 1 or more of the 4 cognitive domains (from cognitive battery); 3) essentially normal functional activities (from the CDR and the FAQ); and 4) absence of dementia (DSM-IV).^4,18 Subjects with MCI were categorized as having amnestic MCI (a-MCI) if the memory domain was impaired or nonamnestic MCI (na-MCI) if there was no impairment in memory.

A diagnosis of dementia was based on the criteria in the DSM-IV.¹⁸ Subjects were characterized as cognitively normal according to published normative data developed on this community.¹³ The cognitive status of subjects as measured at the time of the in-person examination was assumed to be the same as on October 1, 2004. This retrodating of cognitive status allowed us to compute point prevalence figures using October 1, 2004, as the prevalence day.

Statistical analyses.

For the 4 age and sex strata included in the original sampling scheme, point prevalence was computed directly by dividing the number of prevalent cases of MCI by the population in the corresponding stratum (age- and sex-specific prevalence figures for men aged 70–79 and 80–89 years, and women aged 70–79 and 80–89 years). Whenever multiple strata were combined, the estimate for each stratum was weighted by its frequency in the total Olmsted County population (direct standardization to the Olmsted County population on October 1, 2004).¹⁹ Similarly, prevalence figures by education, marital status, and APOE genotype were standardized by age and sex. In our primary analyses, we estimated the prevalence of MCI considering only the population without dementia in the denominator. However, in secondary analyses, we also included subjects with dementia in the denominator. The denominators including dementia were obtained by incorporating and reproportioning both the subjects with previously diagnosed dementia who were excluded from the study and those found at the in-person evaluation.

To investigate possible biases caused by the subjects who did not participate in the study, we used the propensity score method.^3,20 Information for nonparticipants was available from the medical records-linkage system for 97% of all subjects originally sampled.⁸ First, we used logistic regression models to estimate the effect of age, sex, and years of education on participation.^20,21 Second, we used the reciprocal of the participation probabilities for each subject as weights to estimate MCI prevalence figures adjusted for nonparticipation. Although estimates adjusted for nonparticipation were similar to the unadjusted estimates, the primary results presented in tables and figures are all adjusted for nonparticipation.

We also conducted a set of case-control analyses comparing the 329 subjects found to have MCI (prevalent MCI) with the 1,640 subjects who were found to be cognitively normal. For several demographic variables, we computed prevalence odds ratios (OR) and 95% confidence intervals (CI) adjusted for age (≥80 vs <80 years), sex, years of education (≤12 vs >12 years), and nonparticipation (reciprocal probability weighting) using logistic regression models.

To explore the higher prevalence of MCI in men, we investigated the possible confounding effect of several clinical comorbidities (diabetes, hypertension, stroke, coronary heart disease, depression), the Charlson index of comorbidity (<2 vs ≥2), and APOE genotype (carriers vs noncarriers of ε4). We also assessed potential confounding effects of type of informant (spouse or offspring vs other [e.g., more distant relatives, caregivers]) and marital status (currently married vs previously married or never married). All models also included age and years of education. Finally, we assessed potential effect modification by these same variables by including interaction terms with sex in the logistic regression models.

Overall results.

Of the 2,050 subjects who participated in the in-person evaluation, 67 (3.3%) had a dementia that had not been detected by our review of the medical records, 14 (0.7%) had incomplete cognitive testing, 1,640 (80.0%) were cognitively normal, and 329 (16.0%) had MCI (figure 1). Among subjects with MCI, 237 (11.6%) had a-MCI (145 [7.1%] single domain; 92 [4.5%] multiple domain) and 92 (4.5%) had na-MCI (69 [3.4%] single domain; 23 [1.1%] multiple domain).

Table 1 shows the characteristics of the 1,969 subjects who received a cognitive evaluation and were free of dementia. Consistent with the study design, there were about equal proportions of men and women; 53.3% had >12 years of education, and 61.5% were currently married; a greater proportion of men (81.9%) compared with women (40.2%) were currently married. Approximately 23% of subjects had the APOE ε3ε4 or ε4ε4 genotype.

Table 1 Characteristics of the study population without dementia in men and women

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The prevalence of MCI in the total population (including dementia cases in the denominator) and adjusted for nonparticipation was 14.3% for any MCI, 9.9% for a-MCI, and 4.4% for na-MCI (table 2, footnotes). The prevalence of dementia was 10.0% (95% CI 8.9–11.2), and 75.7% of subjects (95% CI 74.1–77.4) were cognitively normal (data not shown). The combined prevalence of either MCI or dementia was 24.3% (95% CI 22.6–25.9; data not shown). Table e-1 (on the Neurology® Web site at www.neurology.org) shows the distribution of the subjects with MCI by the type of concern about cognitive performance and by sex.

Table 2 Prevalence of all MCI, amnestic MCI, and nonamnestic MCI by age, sex, and other characteristics

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MCI prevalence in the population without dementia.

Table 2 shows the prevalence, adjusted for nonparticipation, of all MCI, a-MCI, and na-MCI by age and sex among subjects without dementia. The overall age- and sex-adjusted prevalence of MCI was 16.0% for any MCI, 11.1% for a-MCI, and 4.9% for na-MCI. The prevalence of MCI increased with increasing age and was consistently higher in men than women across all ages (figure 2A). The age and sex patterns were similar for all MCI, a-MCI, and na-MCI. In addition, the increase with age was similar across subtypes of MCI (figure 2C and table e-2). The median FAQ score was 0.0 (interquartile range 0.0–1.0; mean 0.61; SD 1.53) in cognitively normal subjects and 1.0 (interquartile range 0.0–4.0; mean 3.10; SD 4.55) in subjects with MCI. Prevalence figures adjusted for nonparticipation (primary results in tables and figures) were somewhat higher than those unadjusted (e.g., the unadjusted overall prevalence of MCI was 14.9%; 95% CI 13.7–16.0).

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Figure 2 Patterns of mild cognitive impairment (MCI) prevalence by age, sex, education, and type of MCI

(A) Age- and sex-specific prevalence of MCI in Olmsted County, MN. Men had consistently higher prevalence than women at all ages. (B) Education- and sex-specific prevalence of MCI. The prevalence decreased with increasing education in both men and women. (C) Age- and type-specific prevalence of MCI. The increase of prevalence with age was consistent for single-domain amnestic MCI (SD a-MCI), multiple-domain amnestic MCI (MD a-MCI), single-domain nonamnestic MCI (SD na-MCI), and multiple-domain nonamnestic MCI (MD na-MCI). (D) Education- and type-specific prevalence of MCI. The decline in prevalence with increasing education was consistent across the 4 types of MCI.

Table 2 also shows the prevalence of MCI by years of education, marital status, and APOE genotype in men and women separately. The prevalence of MCI decreased markedly with increasing number of years of education from 30.2% in subjects with <9 years of education to 11.0% in subjects with >16 years of education. The pattern was similar for men and women (figure 2B) and across subtypes of MCI (figure 2D and table e-2). The prevalence of MCI was higher in never married subjects than in currently married or previously married subjects, and in subjects with the APOE ε3ε4 or ε4ε4 genotype (table 2).