Functional impairment in elderly patients with mild cognitive impairment and mild Alzheimer disease

Abstract

Context: The original mild cognitive impairment (MCI) criteria exclude substantial functional deficits, but recent reports suggest otherwise. Identifying the extent, severity, type, and correlates of functional deficits that occur in MCI and mild Alzheimer disease (AD) can aid in early detection of incipient dementia and can identify potential mechanistic pathways to disrupted instrumental activities of daily living (IADLs).

Objectives: To examine the number, type, and severity of functional impairments and to identify the clinical characteristics associated with functional impairment across patients with amnestic MCI (aMCI) and those with mild AD.

Design: Study using baseline data from the Alzheimer's Disease Neuroimaging Initiative.

Setting: Multiple research sites in the United States and Canada. Patients Samples included 229 control individuals, 394 patients with aMCI, and 193 patients with AD.

Main outcome measure: The 10-item Pfeffer Functional Activities Questionnaire (FAQ) assessed function.

Results: Informant-reported FAQ deficits were common in patients with aMCI (72.3%) and AD (97.4%) but were rarely self-reported by controls (7.9%). The average severity per FAQ deficit did not differ between patients with aMCI and controls; both were less impaired than patients with AD (P < .001). Two FAQ items (remembering appointments, family occasions, holidays, and medications and assembling tax records, business affairs, or other papers) were specific (specificity estimate, 0.95) in differentiating the control group from the combined aMCI and AD groups (only 34.0% of patients with aMCI and 3.6% of patients with AD had no difficulty with these 2 items). The severity of FAQ deficits in the combined aMCI and AD group was associated with worse Trail Making Test, part A scores and smaller hippocampal volumes (P < .001 for both). Within the aMCI group, functionally intact individuals had greater hippocampal volumes and better Auditory Verbal Learning Test 30-minute delay and Trail Making Test, part A (P < .001 for each) scores compared with individuals with moderate or severe FAQ deficits. Patients with a high number of deficits were more likely to express the apolipoprotein ε4 allele (63.8%) compared with patients with no (46.8%) or few (48.4%) functional deficits.

Conclusions: Mild IADL deficits are common in individuals with aMCI and should be incorporated into MCI criteria. Two IADLs--remembering appointments, family occasions, holidays, and medications and assembling tax records, business affairs, or other papers--appear to be characteristic of clinically significant cognitive impairment. In patients with aMCI, impairment in memory and processing speed and greater medial temporal atrophy were associated with greater IADL deficits.

Figure 1. Post hoc adjusted mean comparisons of neuropsychological predictors of functional deficits in the amnestic mild cognitive impairment sample

Means adjusted for age, sex, and educational level. A and B, Severity of functional deficits. C and D, Number of functional deficits. A significant difference was found in post hoc comparisons between no deficits and mild or few for the severity of functional deficits and the number of functional deficits as measured by the Auditory Verbal Learning Test (AVLT) 30-minute delay. A significant difference was found in post hoc comparisons between no deficits and moderate to severe or high deficits for all measures. A significant difference was found in post hoc comparisons between mild or few and moderate to severe or high deficits for all measures. Severity groups were defined as follows: no deficits, 0; mild severity, 1 or more and 4 or less; and moderate to severe, 5 or more. Number of deficit groups were defined as follows: no deficits, 0; few deficits, 1 or more and 3 or less; and high number deficits, 4 or more. (P < .0167, Bonferroni corrected).

Figure 2. Post hoc adjusted mean comparisons of neuroanatomical predictors of functional deficits in the amnestic mild cognitive impairment sample

Means adjusted for age, sex, and educational level, (and intracranial volume in the hippocampal volume analysis). A, Severity of functional deficits. B, Number of functional deficits. A significant difference was found in post hoc comparisons between no deficits and moderate to severe or high deficits. Severity groups were defined as follows: no deficits, = 0; mild severity, 1 or more and 4 or less; moderate to severe, 5 or more. Number of deficit groups were defined as follows: no deficits, 0; few deficits, 1 or more and 3 or less; and high number deficits, 4. or more (P <.0167, Bonferroni corrected).