Our results, derived from a large multicenter database, indicate that mild IADL deficits are present in both amnestic and nonamnestic MCI, with more extensive deficits reported by informants for amnestic subjects. The degree of IADL impairment was similar between amnestic subjects with single or multiple domains of cognitive impairment. Across all MCI subtypes, global IADL measures were associated with neuropsychological assessments of memory and executive function/processing speed.
Previous studies of IADLs in cognitive subtypes of MCI have produced mixed results. Some investigators have found IADL deficits only in participants meeting criteria for mdAMN MCI [16
]. Others have also found deficits in single-domain (both amnestic and nonamnestic) MCI [14
] that are similar to those reported here. These disparate results may be attributable to differences in IADL demands across cultures, population demographics, or IADL and/or cognitive assessments across studies.
We additionally found more profound IADL limitations in amnestic relative to nonamnestic MCI, which has not been consistently reported in prior studies. Wadley et al. [14
] reported greater deficits in their amnestic MCI subgroup, while Burton et al. [30
] found similar deficits in amnestic and nonamnestic MCI, but more extensive impairment amongst subjects with deficits in multiple cognitive domains. More recent work by Aretouli and Brandt [31
] included two separate IADL assessments, yielding conflicting results that concur with both earlier studies. We were somewhat surprised to find similar IADL deficits in our sdAMN and mdAMN MCI groups. Our initial prediction, given earlier studies of IADLs in MCI subtypes [16
], the consistent association between IADL impairment and progression to dementia [10
], and higher rates of progression to dementia in mdAMN MCI [4
], was that scores on global FAQ indices would be higher in our mdAMN MCI group.
There are several potential explanations for these results. The presence of memory deficits may play a larger role than the presence of additional cognitive deficits in determining IADL impairment. This interpretation is supported by our regression analyses, which indicated that memory performance was an independent predictor of global FAQ indices, and by earlier work from other groups identifying the importance of memory function in the performance of IADLs [21
]. Nevertheless, other investigators have identified executive function as the strongest neuropsychological predictor of IADL abilities [22
], though such discrepancies may be related to differences in the specific tests that comprise cognitive domain scores across studies. Alternatively, subjects in the UDS database with deficits in memory and other cognitive domains who exhibited greater IADL impairments may have been diagnosed with dementia and therefore been excluded from this analysis. Finally, the FAQ may be more heavily weighted towards memory-dependent IADLs than other IADLs. This last possibility seems less likely given previous work showing that total FAQ scores correlate reasonably well with other IADL indices [33
] and that the sdAMN and mdAMN MCI groups in the current cohort had similar scores on each FAQ item (p > 0.05).
The important contribution of memory deficits to impaired IADLs suggested by differences in global FAQ indices between clinically diagnosed amnestic and nonamnestic MCI groups is further supported by regression analyses incorporating neuropsychological performance, which identified both memory and executive/processing speed as significant predictors of functional ability. However, the correlations between cognitive and IADL indices were relatively modest. The strength of these correlations may have been limited by the inclusion of only MCI subjects in the regression analyses, thus restricting the range of both the cognitive and FAQ scores. Some of the prior studies demonstrating more robust correlations between cognitive and functional scores included a broader spectrum of subjects, often encompassing both normal and impaired cognition [22
]. The relatively limited battery of neuropsychological tests included in the UDS may also have reduced the strength of these correlations. In particular, the memory factor includes only two measures from a single test of verbal memory (WMS-R logical memory), and the executive/processing speed factor includes only a single test (Trail-Making Test Part B) that is associated with executive functioning [45
]. Finally, these relatively weak correlations may simply reflect the possibility that similar IADL deficits may be caused by different cognitive deficits in different subjects.
MCI subjects were less likely to have complete FAQ data than NC subjects. The underlying reason for this finding remains uncertain. One possibility is that informants for the MCI groups may have been less knowledgeable about their subjects than informants for the NC group. However, given that similar results were obtained with total FAQ scores (which included only subjects with complete FAQ data) and mean FAQ item scores (which included all subjects), it is unlikely that the differences between groups in the number of valid FAQ responses significantly affected our conclusions.
There are a few other considerations that impact the interpretation of our results. The study population was comprised of a convenience sample of highly educated subjects volunteering for research at major academic centers and therefore may not be representative of epidemiological samples or those with greater ethnic diversity. Nonamnestic MCI subjects were less likely to be non-Hispanic Whites, a finding that replicates other recent studies of nonamnestic MCI [46
] and is consistent with previous reports of poorer performance on nonmemory cognitive assessments in non-White populations [48
]. Our amnestic MCI subgroups were older and included higher proportions of women than the other diagnostic groups. Although similar age differences have been reported in previous studies of amnestic MCI, such gender differences have not [50
]. Diagnostic classification in the UDS is derived from clinical diagnoses determined at each individual ADC based upon the current criteria for MCI [1
]. However, the operationalization of these criteria has not been consistently standardized. Although the UDS includes a core neuropsychological battery [32
], the NACC does not specify which additional cognitive tests can be used at each ADC to supplement that battery, does not establish specific performance thresholds for impairment, and does not stipulate the precise role of test scores in the diagnostic process. Since the specific neuropsychological tests and performance thresholds used to identify MCI can significantly influence subject classification [46
], it remains possible that variability in the interpretation of the diagnostic criteria for MCI across participating centers may have influenced our results. Finally, the FAQ is an informant-based assessment of IADLs, and may be susceptible to bias if informants lack or distort information regarding subjects’ functional abilities. Performance-based measures of IADLs may have better ecological validity, correlate more closely with cognitive function, and allow for more subtle distinctions among diagnostic groups [54
Our cross-sectional findings, when taken together with previous longitudinal reports [10
], raise the possibility that cognitive and functional deficits in MCI may independently contribute to increased risk of subsequent dementia. Although mdAMN MCI subjects have been considered the most likely to progress to dementia, their IADL deficits were similar to those seen in sdAMN MCI subjects. Conversely, although memory and executive/processing speed were independently associated with IADL performance, correlations between cognitive and functional decline were relatively modest. These results provide further support for inclusion of both cognitive and functional variables when estimating dementia risk in MCI [10
] but require further exploration with additional longitudinal analyses.