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Correlates of Disability Among Elderly Retirees With "Subclinical" Cognitive Impairment

^a Departments of Psychiatry, South Texas Veterans' Health System Audie L. Murphy Division GRECC and the University of Texas Health Science Center, San Antonio
^b Departments of Medicine, South Texas Veterans' Health System Audie L. Murphy Division GRECC and the University of Texas Health Science Center, San Antonio
^c Departments of Pharmacology, South Texas Veterans' Health System Audie L. Murphy Division GRECC and the University of Texas Health Science Center, San Antonio

Donald R. Royall, Department of Psychiatry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-7792 E-mail: royall{at}uthscsa.edu.

William B. Ershler, MD

	Abstract

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Background. We assessed the effects of impaired Executive Control Function (ECF) on Instrumental Activities of Daily Living (IADL) and level of care among noninstitutionalized elderly retirees with "subclinical" cognitive impairment.

Methods. Subjects (N = 561; age 78.2 ± 5.0 years) were residents of a single, 1500 bed, continuing care retirement community. Subjects were examined for cognitive impairment using the Executive Interview (EXIT25), Mini-Mental State Examination (MMSE), and an executive clock-drawing task (CLOX). The CLOX is divided into executively sensitive (CLOX1) and simple constructional (CLOX2) subtests.

Results. Residents in congregate high-rises (n = 301) differed significantly from those in independent-living apartments (n = 260) with respect to age, gender, percent living alone, EXIT25, CLOX1, MMSE, and CLOX2 scores (all p < .03). Only differences in ECF measures persisted after adjusting for age and living alone ( p < .004). The EXIT25 ( p < .006) and CLOX2 ( p = .02) were associated with the use of prostheses. The differences in EXIT25 scores persisted after adjusting for level and living alone ( p = .01). All instruments distinguished residents with impairment in IADLs. However, only CLOX2 ( p < .001), EXIT25 ( p < .001), and age ( p < .001) made significant independent contributions.

Conclusions. ECF has statistically significant effects on level of care and IADL impairment, even among noninstitutionalized retirees. This emergent disability is not well detected by traditional global cognitive measures. Evaluation and treatment may be delayed unless ECF measures are employed.

IN 1994, the American Psychiatric Association added impairment of executive control function (ECF) to its list of domains that can be used to establish a diagnosis of dementia ⁽¹⁾. Executive functions control the sequencing and execution of complex goal-directed activities (e.g., cooking, dressing, shopping, and housework). It may not be surprising then that ECF impairment has emerged as a robust determinant of functional status and disability. Alzheimer's disease (AD), Parkinson's disease, vascular dementia, major depression, diabetes mellitus, Human Immunovirus infection, and schizophrenia are all associated with either ECF impairment or frontal system pathology, which has been associated with ECF impairment ^{(2)(3)(4)(5)(6)(7)}. Thus, ECF impairment may serve as a convenient basis on which to compare the severity of these disorders ⁽⁸⁾.

The association between ECF and functional status has not been fully investigated. Traditional tests of global cognitive function are often insensitive to ECF, or ignore it altogether. Consequently, epidemiological or treatment studies may be underestimating the true prevalence and/or the functional impact of dementia ⁽⁹⁾. For example, the International Working Group on Harmonization of Dementia Drug Guidelines recently recommended cognitive measures to be used in dementia assessment ⁽¹⁰⁾. Although the need to measure ECF was acknowledged, none of the instruments recommended were judged to be sensitive to this domain. It is also possible that many ECF-impaired subjects are being misclassified as "minimally" or "subclinically" impaired by "global" measures of dementia that are relatively insensitive to executive control ⁽¹¹⁾.

We have been examining the ability of executive measures to predict level of care among the residents of comprehensive care retirement communities (CCRCs) ^(12)(13). CCRCs are essentially closed systems in which a resident's living setting may change in proportion to the services and supervision they require. In one such facility, only four clinical variables (e.g., executive function, medications, depression, and problem behavior ratings) made significant independent contributions to level of care. Together, they accounted for 69% of the total cross-sectional variance (R² = .69; F[df 7,99] = 32.1; p < .0001). However, an executive measure (the Executive Interview [EXIT25]) made the strongest independent contribution (R² = .48, p < .001) ^(7)(13). In contrast, age, Mini-Mental State Examination (MMSE) ⁽¹⁴⁾ scores, and physical disability ratings did not contribute significantly to level of care, independently of the other variables.

We examined a second cohort of CCRC residents as part of the Air Force Villages' Freedom House Study (FHS). The FHS is a longitudinal study of emergent dementia in a single (1500 bed) CCRC (the Air Force Villages). This sample is unusual in that it is culturally homogeneous (99% Caucasian), highly educated (mean = 15.1 ± 2.4 years), healthy (81% self-rated good to excellent; <10% diabetic or report a history of stroke), and affluent. 92.8% of subjects scored 24 out of 30 on the MMSE. However, despite their relatively high education and excellent health, 40%–80% showed evidence of isolated ECF impairment ⁽¹⁵⁾. This impairment would appear to be subclinical in severity if judged by the MMSE or similar instruments. Nonetheless, ECF-impaired subjects may yet be suffering detectable levels of functional disability, especially if judged against young adults, who display similar general cognitive test scores, but no ECF impairment. In this article, we examine effect of ECF impairment on functional status among the noninstitutionalized FHS participants.

	Subjects

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Elderly retirees (N = 561) were assessed as part of the FHS. Subjects represent a random sample of Air Force Villages' residents over the age of 70 years living at noninstitutionalized levels of care. Data for this analysis were collected in the first year of the study (1994–1995). Informed consent was obtained prior to their evaluations.

	Material and Procedures

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The subjects were rated on ECF, general cognitive function, cross-sectional level of care, instrumental activities of daily living (IADL), and the use of prostheses. Clinical data were obtained by trained clinical research technicians using a structured clinical interview administered in the subject's residence. Information on IADLs and prosthesis usage was elicited directly from the subject and confirmed with a spouse or caregiver, if available. Cognitive measures were administered directly to the subject by a psychometrician in a separate interview, usually conducted within a week of the first.

Cognitive Measures
The EXIT25.-- The EXIT25 ^(7)(16) provides a standardized clinical ECF assessment. It contains 25 items designed to elicit signs of frontal system pathology (e.g., imitation, intrusions, disinhibition, environmental dependency, perseveration, frontal release, etc.). The EXIT25 requires 15 minutes to administer and can be given by nonmedical personnel. Interrater reliability is high (r = .90). It correlates well with other measures of ECF including the Wisconsin Card Sorting Task (WCST; r = .54), Trail-Making Part B (r = .64), Lezak's Tinker Toy test (r = .57), and the Test of Sustained Attention (time, r = .82; errors, r = .83). EXIT25 scores are reported to correlate strongly and specifically with mesiofrontal cerebral blood flow (rCBF) by single photon emission computerized tomography ⁽¹⁷⁾. Scores range from 0 to 50. High scores indicate impairment. A cut point of 15 out of 50 is recommended.

CLOX: an executive clock-drawing task.-- The CLOX ⁽¹⁸⁾ is an even briefer ECF measure based on a clock-drawing task. It is divided into two parts. CLOX1 is an unprompted task that is sensitive to executive control. CLOX2 is a copied version that is less dependent on executive skills. Each CLOX subtest is scored on a 15-point scale. Low scores are impaired. Cut points of 10 out of 15 (CLOX1) and 12 out of 15 (CLOX2) represent the 5th percentiles for young adult controls ⁽¹⁸⁾. In a sample of 196 CCRC residents, we found that both the EXIT25 and CLOX1, but neither the MMSE nor CLOX2, made significant independent contributions to the number of categories achieved on the WCST ⁽¹⁹⁾. The EXIT25 accounts for 68% of CLOX1 variance ⁽¹⁸⁾.

The MMSE.-- The MMSE ⁽¹⁴⁾ is a well-known and widely used test for screening cognitive impairment ⁽²⁰⁾. Scores range from 0 to 30, with scores below 24 reflecting cognitive impairment. In these analyses, the MMSE is considered a proxy for posterior cortical pathology. It has no items that are specifically addressed to ECF ⁽²¹⁾ and may underestimate cognitive impairment in frontal system disorders ^(6)(11).

Functional Status Measures
Level of care.-- The Air Force Villages CCRC provides services at three levels of care. These include independent-living apartments (level 1), in which essentially no services are provided; congregate high-rises (level 2), in which laundry, housecleaning, meals, and medication supervision are provided; and skilled nursing units (level 3), in which residents are provided with assistance in their Activities of Daily Living (ADLs), nursing care, and medications. Only noninstitutionalized residents living at levels 1 or 2 were included in this analysis.

IADLs.-- IADLs were assessed using the Older American Research and Service Center Instrument (OARS) ⁽²²⁾. The OARS instrument is a multidimensional-assessment tool that provides information in three domains likely to influence functional outcomes in the setting of executive dyscontrol: social resources, physical health, and IADLs. In addition, the OARS services utilization section provides data on the quantity and quality of services provided to subjects by their caregivers. These sections of the OARS have been independently validated and can be administered separately (Greda Fillenbaum, personal communication, 1992).

	Results

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Table 1 presents the mean demographic characteristics and clinical test scores for the total sample (N = 561) and both levels of care. Residents in congregate high-rises (n = 301) differed significantly from those in independent-living apartment settings (n = 260) with respect to age, gender, percent living alone, EXIT25, CLOX1, MMSE, and CLOX2 scores (all different by analysis of variance [ANOVA] [1,559], p < .03). The differences in age, CLOX1, MMSE, and EXIT25 scores survived Bonferroni correction to p < .007.

We also examined the relative ability of the EXIT25, CLOX1, MMSE, and CLOX2 to distinguish between residents at each level of care by dichotomizing the subjects' test scores at each instrument's established cut points (EXIT25 = 15 out of 50; CLOX1 = 10 out of 15; MMSE = 24 out of 30; CLOX2 = 12 out of 15). After adjusting for age and living alone, a multivariate analysis of covariance (MANCOVA) was significant [df (4,553) Wilks's =.97, p < .003]. However, in post hoc tests, only executive measures (EXIT25 [ p < .002] and CLOX1 [ p < .001]) made significant contributions independent of the other variables (Tukey's Honest Significant Difference Test for unequal NS).

Cognitive impairment had significant effects on the use of adaptive devices. The EXIT25 (ANOVA: F [1,556] = 7.62, p < .006) and CLOX2 (ANOVA: F [1,556] = 5.16, p = .02) were significantly associated with the use of any prosthesis, including a hearing aid, cane, or walker. The EXIT25's ability to distinguish these groups persists after adjusting for level of care and living alone (ANCOVA: F [1,553] = 6.31, p = .01). CLOX2 shows a trend (ANCOVA: F [1,551] = 3.67, p = .06). However, CLOX2 cannot distinguish residents' use of prostheses after adjusting for the EXIT25 (ANOVA: F [1,553] = 2.81, p = NS). Interestingly, the effects of ECF impairment on prosthesis usage and level of care were in the opposite directions (Fig. 1). Passing the EXIT25 was associated with the increased use of prostheses and a lower average level of care. Failing the EXIT25 was associated with a higher risk of congregate high-rise placement and diminished use of prostheses and adaptive devices.

View larger version (13K): [in this window] [in a new window]   Figure 1. EXIT25 performance and its effects on prosthesis use and level of care. Rao R (2,558) = 9.07; p = .0001.

	Discussion

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This study confirms that impairment in ECF has statistically significant effects on level of care and functional status. This is consistent with our previous observation that ECF is a major determinant of cross-sectional level of care within the CCRC setting ⁽¹³⁾. However, this analysis goes beyond that earlier work in three important ways. First, this sample is taken from a second CCRC, suggesting that our earlier finding of a strong association between ECF and level of care was not limited to local factors in a single facility. Second, this is a random sample. The earlier study examined a convenience sample. Third, these subjects were not institutionalized at the time of their assessment. We have essentially detected incipient disability among relatively high functioning retirees. Because the FHS is a longitudinal study, we will eventually be able to examine the effects of ECF impairment on these residents' time to institutionalization and other transitions within the CCRC system.

Only ECF measures (EXIT25 and CLOX1) had a significant independent effect on cross-sectional level of care. This was robust, surviving adjustment for age, percent living alone, and Bonferroni correction. We have previously shown that the EXIT25 makes a strong independent contribution to level of care in CCRC residents ^(7)(13). CLOX1 (but not CLOX2) shares this property. Similarly, Grace and coworkers ⁽²³⁾ report that CLOX1 (but not CLOX2) is a significant independent predictor of "life space" (a measure of functional autonomy) among elderly community residents. CLOX1 has been specifically designed to measure ECF. In fact, CLOX1 is more "executive" than several other comparable clock-drawing tasks ⁽²⁴⁾.

It is important to notice that the ECF impairment detected by the EXIT25 and CLOX1 is not well detected by the MMSE. The mean MMSE score for this sample was 27.7 ± 2.8. Of this sample, 92.8% scored 24 out of 30. Nonetheless, 30.8% failed the EXIT25 at 15 out of 50. In our earlier CCRC study, 55% of subjects who scored 24 on the MMSE failed the EXIT25 at 15 out of 50 ⁽¹³⁾. Similarly, in a recent study of type 2 diabetic patients from outpatient medical settings, 89.6% passed the MMSE at 24 out of 30 (mean MMSE = 26.1 [3.1]), but 59.7% failed the EXIT25 ⁽²⁵⁾.

The prevalence of ECF impairment in community samples has not been well studied, but is also likely to be very common. Elderly independent-living community residents (25.5% of N =1145) showed impairment on a brief ECF-screening instrument, the Behavioral Dyscontrol Scale (BDS) ^(26)(27). Half of these had normal MMSE scores. The BDS was a stronger predictor of impaired functional status than the MMSE. Axelrod and coworkers ⁽²⁸⁾ reported that each 1-point decline in MMSE scores among community-dwelling elderly persons represents a statistically significant increase in ECF impairment. These observations suggest that case definitions of "minimal cognitive impairment" derived from MMSE scores (or similar global cognitive screening measures) will consistently underestimate the severity of ECF impairment and its effects on functional status.

Moreover, these studies' observations of ECF impairment in the absence of an abnormal MMSE score may have diagnostic significance ⁽¹¹⁾. We have advocated the utility of routinely making the distinction between dementias that present with (type 1) and without (type 2) posterior cortical features ⁽⁶⁾. The MMSE is essentially a proxy for the posterior cortical features of AD. This suggests that an ECF-impaired subject who passes the MMSE has a pattern of cognitive deficits more consistent with a type 2 dementia than "early" type 1 disease ^(11)(29).

Although it is widely presumed that age-associated cognitive impairments overlap seamlessly with cortical (type 1) dementia, old age is most closely associated with a type 2 pattern of isolated ECF deficits ⁽⁶⁾. As the brain ages, frontal neuronal systems suffer disproportionate atrophy ⁽³⁰⁾, hypometabolism ⁽³¹⁾, and structural pathology ⁽³⁰⁾. Even healthy elderly without evidence of either AD or ischemic vascular disease are affected ^{(19)(32)(33)(34)(35)}. Longitudinal follow-up or pathology of our FHS sample will ultimately resolve the question of whether the large number of cases with ECF impairment at baseline have "preclinical" AD or some other condition.

We would also like to draw attention to the apparent dissociation between the individual CLOX subtests and functional status measures. CLOX1 was significantly associated with level of care, but not IADLs. In contrast, CLOX2 was significantly associated only with IADLs. This is unexpected because the EXIT25 was a significant independent predictor of both functional indicators. Why should a constructional clock-drawing task be specifically associated with IADLs?

It may be significant that IADLs were often elicited here as a self-reported measure of disability. In AD, poor performance on constructional tasks has been associated with right temporoparietal changes by functional neuroimaging ^{(36)(37)(38)(39)}. Similar changes can be detected in preclinical subjects at familial and genetic risk for AD ⁽⁴⁰⁾. However, as we discussed above, visuospatial tasks can themselves be conceptualized in terms of both an executive component (measured by CLOX1) and a constructive component (measured by CLOX2).

Anosognosia (the loss of insight) may depend on networks involving both elements ^(41)(42). Insight is impaired among patients with either focal frontal ^(43)(44)(45) or right parietal brain dysfunction ^(43)(44)(46). In AD, tests of ECF and visuospatial function (including clock drawing) are statistically associated with the unawareness of memory loss ^(46)(47) and erroneous self-reported IADL status (relative to caregiver ratings) ⁽⁴⁸⁾.

Subjects who fail both CLOX2 and ECF measures may be at special risk of invalid self-report, regardless of their overall level of dementia. In contrast, CLOX2 did not have a statistically significant effect on the more objective "level of care." Only ECF measures (the EXIT25 and CLOX1) were significant independent predictors of this domain.

In summary, ECF impairment has statistically significant effects on level of care, IADL impairment, and the use of prosthetic devices. This effect can be observed even among noninstitutionalized retirees with normal performance on general cognitive measures. Moreover, it can be elicited with relatively simple measures that could easily be employed in a wide variety of clinical settings. In particular, the CLOX may provide both an ECF assessment that is significantly associated with level of care (CLOX1) and a nonexecutive assessment (CLOX2) that may be related to a subject's capacity to give an adequate self-report. Alternatively, the failure to employ ECF measures could delay evaluation and treatment for cognitive impairment or lead to the diversion of health care resources towards less significant correlates of functional decline. This study examines the association between ECF measures and functional status in nondemented elderly subjects. Longitudinal follow-up will be needed to determine if performance on ECF measures can distinguish subgroups among the community-dwelling elderly population at risk for future progression to frank dementia and/or disability.

	Acknowledgments

 
An abstract of this work has been presented at the 1999 Annual Scientific Meeting of The Gerontological Society of America. The authors wish to acknowledge the cooperation and support they received from the Air Force Villages.

Received August 20, 1999

Accepted December 23, 1999

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