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Brief Report |
Received August 16, 2001; revised January 14, February 21, 2002; accepted February 22, 2002. From the Department of Psychiatry, Brown Medical School, Providence, RI (PAB,RP,TZ,NG,RC), The Miriam Hospital, Providence, RI (RP,TZ,NG,RC), and the Department of Psychiatry, University of Iowa (DM). Address correspondence to Dr. Boyle, Brown University Medical School, Department of Psychiatry, Box G-BH, Providence, RI 02912. e-mail: pboyle{at}lifespan.org
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ABSTRACT |
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Key Words: Vascular Dementia • Rating Scales • MRI
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INTRODUCTION |
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Although diagnostic criteria for VaD require cognitive deficits and neurological findings sufficient to cause functional declines,3,4 the factors associated with IADL impairment remain unclear. VaD patients with severe cognitive impairment typically display greater IADL impairment than do those with mild-to-moderate cognitive impairment,5 as do VaD patients with cortical and subcortical neuropathology, when compared with those with only subcortical neuropathology;5 however, studies have not examined the combined impact of cognitive deficits and neuropathological findings on IADLs in VaD.
Previous findings indicate a selective association between executive dysfunction and IADL impairment in neurologic populations,6 and we recently demonstrated a significant association between executive dysfunction and functional deficits in VaD.7 Much less is known about associations between neuroimaging findings and functional abilities in neurologic populations, although the presence of subcortical hyperintensities (SH) has been shown to contribute to IADL impairment in depressed geriatric patients, even after we account for cognitive dysfunction.8 SH is common in VaD and may contribute to functional impairment over and above cognition,5,9 but studies have not investigated the unique relationship between subcortical hyperintensities and IADLs in VaD.
The purpose of this study was to examine associations between cognitive functions, neuroimaging findings, and IADLs in VaD. Our hypotheses were the following: 1) Executive cognitive abilities and SH are significantly associated with IADLs in patients with VaD; and 2) executive cognitive abilities and SH make independent contributions to the prediction of IADLs in VaD—more specifically, SH accounts for unique variance beyond that accounted for by executive abilities.
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METHODS |
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Procedures
Data for this study were collected at the baseline evaluation for the pharmacologic trial. Participants were administered the Dementia Rating Scale10 as part of a comprehensive neuropsychological assessment battery. The Dementia Rating Scale provides estimates of global cognitive functioning and five cognitive skill areas (Attention, Initiation/Perseveration [IP], Conceptualization, Memory, and Construction). The Dementia Rating Scale was administered according to standard procedures, and total and subscale raw scores were calculated by summing points obtained on subscale items. Scores on the IP subscale correlate significantly with other executive tasks,6 and the IP subscale was used as a measure of executive cognitive functioning in this study.
For the assessment of IADLs, primary caregivers were administered the IADL portion of the Lawton and Brody Activities of Daily Living (ADL) Questionnaire,2 designed to assess independent living abilities. This subscale consists of eight questions pertaining to IADLs (e.g., ability to handle finances, manage medications, perform household duties). Each question was scored using procedures reported in previous research;5,8 item scores of 0 reflect independence in task performance; a score of 1 reflects the need for some assistance, and 2 indicates complete dependence on others for task performance. Item points were summed to compute IADL total scores (with higher scores reflecting poorer IADL performance; maximum score: 16).
On the day after the cognitive and functional assessments were performed, participants underwent MR neuroimaging. Imaging procedures and volumetric analysis techniques for quantifying SH and cortical volume have been described in detail elsewhere.5 Briefly, a 1.5-tesla Siemen's scanner was used to obtain FLAIR MR images of the brain. Slices were oriented parallel to the canthomeatal line, and images were taken in 5-mm sections, with a 2-mm interscan gap. Data were downloaded to the MedVision System, which reads proprietary header information for Siemen's MRI scans, and a semi-automated thresholding method was used to select pixel values representing abnormal tissue and lesions in the periventricular areas, including basal ganglia, thalamus, and white-matter tracts. Volume summations of SH were calculated as a ratio of total hyperintense signal over total brain volume (excluding cerebrospinal fluid spaces), and computer-generated estimates of SH were used in the present analyses. To aid in sample characterization: of the 29 participants in this study, 27 were judged by neurologists' ratings as having moderate-to-severe SH, and 2 were judged as having mild-to-moderate SH.
Data Analysis
Data analysis was conducted with the Statistical Package for the Social Sciences (SPSS), and assumptions of normality and equal variance were assessed with standard procedures (e.g., Levine's test for the equality of variance). Pearson correlations were run to examine bivariate associations between cognitive functions, neuroimaging findings, and IADLs, and a planned hierarchical linear regression was run to examine the predictive value of IP and SH in determining IADLs.
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RESULTS |
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Relationships Between Cognitive Functioning and Neuroimaging Findings
Correlational analyses revealed a moderate significant association between SH and IP (r= –0.46; p= 0.02), but SH was not related to the Dementia Rating Scale total or other subscale scores. In contrast, cortical volume correlated significantly with the Dementia Rating Scale total (r=0.48; p=0.02) and the Memory subscale (r=0.59; p=0.003). Cortical volume was not significantly correlated with any other subscale, and SH and cortical volume were not significantly correlated (r= –0.24; p=0.25).
Predictive Relationships Between Executive Abilities, SH, and IADLs
A planned hierarchical linear-regression analysis was conducted to examine the independent contributions made by IP and SH to IADLs; IP was entered at Step 1 and SH at Step 2. The overall model accounted for 42% of the variance in IADLs (R[2,25]=0.65; p=0.009; R2=0.423; overall F=6.23) and, as predicted, both variables were significantly associated with IADLs. IP alone accounted for 28% of the variance in IADLs (p=0.017), and SH added 14% (p=0.04) over and above the contribution made by IP.
Finally, a hierarchical regression was run in order to ensure that the above findings did not reflect an age effect. For this analysis, age was entered at Step 1, IP at Step 2, and SH at Step 3, with total IADL as the dependent variable. Age did not significantly affect the prediction equation (p=0.27) and resulted in a mere 2% increase in the variance explained by the model (R2=0.44).
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DISCUSSION |
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The finding that IP was the only Dementia Rating Scale subscale that correlated significantly with IADLs supports our recent findings and related research.6,7 Performance on tests of executive functions may be the most reliable predictor of functional impairment in neurologically impaired elderly patients. Executive functions include complex thinking abilities, mental flexibility, and behavioral initiation and persistence,9 and it follows logically that executive abilities are required for independent living. Individuals with executive dysfunction may have difficulty performing complex activities such as medication management, which requires the initiation of a goal-directed behavior, organization of action, and behavioral persistence.
It is not surprising that executive dysfunction is selectively related to functional abilities in VaD, given that executive dysfunction is a core feature of the disease.7,9 Consistent with earlier findings, our sample exhibited prominent executive deficits. If executive functions are markedly impaired in patients with VaD and are uniquely associated with functional deficits, then a particular focus on the assessment of executive abilities may aid in the diagnosis and treatment of patients with VaD.
Perhaps most importantly, the present results indicate that subcortical neuropathology influences functional ability in patients with VaD independent of executive cognitive impairment. The predictive usefulness of SH in determining IADLs has been demonstrated in depressed geriatric patients,8 but previous studies have not examined the functional significance of SH in VaD. It is important to acknowledge that IP and SH were correlated in the present study, and both reflect disrupted frontal-subcortical functional circuits. Nevertheless, our findings demonstrate that SH affects functional abilities beyond the effect of executive cognitive dysfunction. Both executive dysfunction and SH may therefore be important barometers of independent living skills in patients with VaD.
Methodological limitations that compromise the generalizability of the present findings include the relatively small sample size, the use of only one measure of executive functions, the lack of a measure of neuropsychiatric disturbance, and the analysis of total white-matter burden, rather than regional burden. The inclusion of several tests of executive dysfunction in a larger sample would yield useful information regarding which specific executive functions are involved in the regulation of IADLs. Also, neuropsychiatric symptoms may affect functional abilities, and it is possible that the location of white-matter hyperintensities is as important as total SH burden, or more so. Finally, although research has demonstrated that caregiver-rated estimates of IADLs such as those obtained in the current study are reliable and valid,2 performance-based IADL assessments may yield additional information regarding functional outcomes in VaD. More comprehensive, longitudinal studies are needed to elucidate the factors associated with IADL dysfunction and to better understand the functional significance of subcortical hyperintensities in VaD.
Our finding that executive cognitive and neuropathological factors predict functional impairment in VaD has important implications for the assessment and treatment of patients with this disease. VaD patients with executive dysfunction who have significant subcortical pathology may be at greater risk for functional declines than are those with minimal SH, and healthcare providers should attend to this information when evaluating patients. An improved understanding of the factors associated with disability in VaD may aid in the early identification of individuals in need of assistance and ultimately will inform interventions aimed to prolong independence in aging.
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This article has been cited by other articles:
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  J. K. Johnson, L.-Y. Lui, and K. Yaffe Executive Function, More Than Global Cognition, Predicts Functional Decline and Mortality in Elderly Women J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2007; 62(10): 1134 - 1141. [Abstract] [Full Text] [PDF]
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 D. R. Royall, E. C. Lauterbach, D. Kaufer, P. Malloy, K. L. Coburn, K. J. Black, and The Committee on Research of the American Neuropsy The Cognitive Correlates of Functional Status: A Review From the Committee on Research of the American Neuropsychiatric Association J Neuropsychiatry Clin Neurosci, August 1, 2007; 19(3): 249 - 265. [Abstract] [Full Text] [PDF]
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 J. L. Ingles, D. C. Boulton, J. D. Fisk, and K. Rockwood Preclinical Vascular Cognitive Impairment and Alzheimer Disease: Neuropsychological Test Performance 5 Years Before Diagnosis Stroke, April 1, 2007; 38(4): 1148 - 1153. [Abstract] [Full Text] [PDF]
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 B. T. Mast and J. C. Allaire Verbal learning and everyday functioning in dementia: an application of latent variable growth curve modeling. J. Gerontol. B. Psychol. Sci. Soc. Sci., May 1, 2006; 61(3): P167 - P173. [Abstract] [Full Text] [PDF]
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