Our study yielded four important findings. First, we demonstrated that patients with mild cognitive impairment showed significant compromises on the UPSA, a performance-based measure of everyday function that comprises ecologically relevant tasks. The effect size between the cognitively healthy participants and those with mild cognitive impairment was large (>0.85). Second, when we restricted our analysis to only participants whose everyday function was deemed within normal limits on an informant-based measure, we nevertheless continued to observe significant impairments on the UPSA. Third, we found that cognitive scores in speed of processing, episodic memory, and semantic processing and fluency accounted for a significant share of the variance on the UPSA (about 0.50), thus suggesting a principled relationship between the two types of measures. Fourth, the psychometric properties of the UPSA were good.
Our results indicate that patients with mild cognitive impairment have functional impairments, as indicated on a performance-based measure of everyday functional ability. Moreover, in our stringent and critical analysis of a purified sample, we were able to demonstrate that patients with mild cognitive impairment had impairments even when there was otherwise “objective” informant-based information suggesting preserved function. These results argue against the notion of mild cognitive impairment exceptionalism—that is, the idea that patients with mild cognitive impairment, unlike those with nearly all other neuropsychiatric disorders, and despite their marked impairment in an important domain of cognition, have preserved everyday function.
Early conceptions of mild cognitive impairment suggested that little change would occur in daily function in the face of ongoing cognitive decline (38
). As this view evolved, subtle impairments in instrumental activities were included in the consensus criteria for amnestic mild cognitive impairment (21
). However, the specific instrumental performances of patients with mild cognitive impairment have not been well characterized (38
). Thus, the diagnosis of mild cognitive impairment did not necessarily imply that there were no functional consequences, but rather it indicated that patients did not exhibit gross functional impairment in the course of normal daily activities as observed and reported by a knowledgeable observer but could have subtle, undetected impairment. (See the Patient Perspective box for some of the clinical implications.)
The method we used in this study allowed us to align cognitive and functional impairments. Thus, the majority of the variance in the UPSA could be predicted by key cognitive measures, including verbal episodic memory, semantic processing, executive ability, and speed/attention. This approach also provided convergent validity for findings of compromised function in the mild cognitive impairment group. Moreover, such a principled relationship has often been difficult to discern in informant-based measures of function (39
A pragmatic advantage of performance-based measures is that they are free of the possible informant biases or lacunae in knowledge that may distort informant-based reports. From a psychometric standpoint, the UPSA was also sensitive, was not prone to ceiling or floor effects, and demonstrated acceptable receiver-operating-characteristic curves. As the field moves to earlier diagnostics and interventional strategies, the psychometric strengths of the UPSA also make it attractive. It might also be an appropriate coprimary endpoint in clinical trials of Alzheimer's medications designed to improve cognition and function on instrumental activities. Certainly the need for more sensitive and objective measures of everyday function has been widely discussed in the literature (20
It could be argued that we have created a “straw man” in this article. While several reports have identified functional impairments in cohorts with psychometrically defined mild cognitive impairment (40
), including in one study using a narrowly based performance-type measure of function (44
), no study has directly contrasted performance-based and informant-based measures, as we did here, and provided empirical support for the predictions that the magnitude of these compromises are large and can be robustly and systematically related to cognitive failures in mild cognitive impairment and Alzheimer's disease. In this manner, it becomes possible to place our results within a broader context of neuropsychiatric disorders so as to better understand the implications of a variety of cognitive impairments for function. Moreover, we note the rather large number of studies of mild cognitive impairment in which preserved function remains a diagnostic criterion, along with its implicit assumptions.
It should be noted that the ADCS-ADL was designed for a very different purpose than that used here, namely, to stage decline in Alzheimer's disease. We deployed it to bring into sharper relief points about conceptualizing mild cognitive impairment, performance-based measures of function, and the pragmatics of assessing function at earlier points in the Alzheimer's disease process. Even so, the effect size of 0.56 that we observed on this measure was moderate and would have been statistically significant in a larger sample. Newer versions of the test specifically tailored to emphasize the more complex activities that are likely to be impaired in mild cognitive impairment show much promise (45
). These issues can be thought of as involving detection and sensitivity, which may in turn be dependent on what is being asked and who is being asked. Of course, both types of scales (informant-based and performance-based) need to address cultural variability and sensory and motor disabilities.
Several criticisms have been raised about performance-based measures. These include the idea that they are neuropsychological tests by another name. Our view is more nuanced, in that we believe that the analogue tasks in performance-based measures engage fundamental cognitive operations. We believe that the UPSA is ecologically valid because it assesses the performance of tasks that must be frequently and efficiently managed by individuals living in the United States and similar cultures. The tasks tested by the UPSA are important in and of themselves and may be surrogates for a wider range of activities (e.g., remembering key documents to bring to a doctor's office in the UPSA assessment may also have relevance to remembering documents or items to bring to other types of appointments). Our multiple regression results empirically support this argument. Another argument has to do with the possibility that these measures may be too sensitive—that patients appear to be doing well in their home environment but score poorly on tests. In our view, patients' adaptation to their environment may be dependent on procedural learning and relatively automatic routines that do not accurately reflect the ability to perform more novel, yet ecologically critical, tasks. Such tasks might require the integration of a variety of attentional/speed, semantic, and episodic memory demands that are indirectly captured by the UPSA.
In summary, we found that patients with mild cognitive impairment had significant impairments on a performance-based measure of everyday function and that the magnitude of the contrast between cognitively healthy participants and those with mild cognitive impairment (in effect size units) was greater for the performance-based measure than for an informant-based measure. Furthermore, as predicted, we found a strong relationship between cognitive performance and the performance-based measure of function using multiple regression models. Our work also suggests the need for a reconceptualization of the relationship between cognition and function in mild cognitive impairment so that they can more effectively be aligned.
“Mrs. B,” a 76-year-old woman, has a 2-year history of memory problems marked by forgetfulness, asking occasionally repetitive questions (e.g., about when an appointment is to occur), and mild word-finding problems. Both she and her husband characterized the impairment as “short-term memory problems.”
The patient's history was remarkable for a 10-year history of hypercholesteremia and a 6-year history of hypertension. Neurologic examination was notable for the presence of motor sequencing difficulties. No aphasic, apraxic, or agnostic symptoms were observed. An MRI report noted the presence of mild lateral ventricular enlargement and “cerebral atrophy consistent with age.” The patient's psychiatric history was notable for a single depressive episode approximately 20 years ago successfully treated with a selective serotonin reuptake inhibitor.
There was no family history of late-onset dementia. The patient had a score of 2 on the Geriatric Depression Scale, which did not indicate the presence of current clinical depression. A Hachinski Ischemic Score of 2 suggested that the patient was not at high risk for vascular-related cognitive changes.
At home, Mrs. B sometimes misplaces personal items but can usually find them. She can hold conversations and make relevant remarks. She no longer drives; her husband does. She has no difficulty with grooming, toileting, eating, or dressing. She is also able to cook and clean. She is able to shop, use a list, and receive change. Her husband noted that she can do most tasks, but it takes her longer to do them. Socially, Mrs. B sees friends and relatives somewhat less frequently than before because she worries that she cannot keep up with a conversation, takes less pleasure from interactions, and “forgets things.”
On psychometric assessment, Mrs. B's Mini-Mental State Examination score was 26 (above the cutoff for dementia); she lost points in word recall and orientation. Her Clinical Dementia Rating score was 0.5 (consistent with mild cognitive impairment). On a verbal list learning test measuring episodic memory (selective reminding), Mrs. B's learning curve over six trials was blunted. On trial 6 she recalled five of 12 words, and after a 30-minute delay she was unable to recall a single word and could not recall that she had been presented with the list earlier. This suggested an accelerated rate of forgetting and possibly difficulties in consolidation. Other memory tests, including memory for stories, were similar in pattern. Tests of speed of processing, including the Trail Making Test and verbal fluency for letters, indicated mild to moderate impairment. On the clock test, which involved drawing a clock with the time set at “10 after 11,” Mrs. B's drawing was marginally intact. Numbers and hands on the clock were placed accurately, but the hands were of equal length. Performances in other domains of function were within normal limits or were near normal.
On the Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory, Mrs. B's husband noted few problems. Points were lost in use of appliances beyond on/off controls and recall of information from reading more than an hour later. The overall score was 76 of 78 points (97% accuracy). These results suggest that Mrs. B's daily functioning, while not quite optimal, is relatively well preserved and that she can negotiate her environs with some support from her husband. This score might also reflect the fact that she is in a familiar setting and that certain tasks have been routinized.
On the UCSD Performance-Based Skills Assessment (UPSA), Mrs. B demonstrated compromised functional capacities; her accuracy was 78%. Among errors on simulated tasks, she did not remember several items to take on a trip to the beach, she forgot documents to bring to a doctor's appointment, and she had difficulty determining a bus route using a lookup table. She also omitted some information while filling out a check to be made out to an electric company (based on a complicated bill). These ecologically valid tasks may suggest that Mrs. B could experience difficulties with tasks somewhat outside her comfort zone. In effect, Mrs. B functions well in a familiar environment with support from her husband. The UPSA indicates that she may have more difficulty on novel or less routine tasks where her compromised cognitive abilities must fully be brought to bear.
Mrs. B's diagnosis was mild cognitive impairment, “amnestic plus” subtype.