Abstract
ObjectiveTo compare the rate of cognitive and functional decline in dysexecutive, typical and amnestic subgroups of Alzheimer’s disease.Methods943 participants from the National Alzheimer’s Coordinating Center (NACC) database who had a diagnosis of probable AD were followed for a mean of 2.3 years. A dysexecutive subgroup (n = 165) was defined as having executive performance >1.5 SD worse than memory performance, an amnestic subgroup (n = 157) was defined as having memory performance >1.5 SD worse than executive performance and a typical subgroup (n = 621) was defined as having a difference in executive and memory performance of <1.5 SD. Generalized estimating equations (GEE) were used to model decline on the Folstein Mini Mental Status Exam (MMSE), rise on the Clinical Dementia Rating (CDR) sum of boxes and rise on the total Functional Assessment Questionnaire (FAQ).ResultsCompared with the amnestic subgroup, the dysexecutive subgroup declined 2.2X faster on the Folstein MMSE (p<.001), rose 42% faster on the CDR sum of boxes (p = .03) and rose 33% faster on the total FAQ (p = .01). Rate of change for the typical subgroup fell between that of the amnestic and dysexecutive subgroups for the MMSE, CDR sum of boxes and total FAQ. Among a subset of participants (n = 129) who underwent autopsy, the dysexecutive, amnestic and typical subgroups did not differ in odds of having an AD pathologic diagnosis, suggesting that variation in non-AD pathologies across subtypes did not lead to the observed differences.ConclusionsA dysexecutive subgroup of AD has a unique disease course in addition to cognitive phenotype.
Highlights
While Alzheimer’s disease (AD) ‘‘classically’’ presents with predominant episodic memory deficits [1], in actuality, the presentation can be quite heterogeneous
Structural and functional imaging studies suggest that AD patients with predominant executive dysfunction have greater frontoparietal cortical thinning and hypometabolism than healthy controls as well as AD patients with predominant memory deficits [8,9]
We and others have found that the APOEe4 allele is less frequent in a dysexecutive subgroup of AD compared with an amnestic subgroup [9,10,11]
Summary
While Alzheimer’s disease (AD) ‘‘classically’’ presents with predominant episodic memory deficits [1], in actuality, the presentation can be quite heterogeneous. We and others have shown that this dysexecutive subgroup of AD has unique genetic, biological, and clinical characteristics compared with typical AD. Structural and functional imaging studies suggest that AD patients with predominant executive dysfunction have greater frontoparietal cortical thinning and hypometabolism than healthy controls as well as AD patients with predominant memory deficits [8,9]. We and others have found that the APOEe4 allele is less frequent in a dysexecutive subgroup of AD compared with an amnestic subgroup [9,10,11]. We have shown that hypertension is less frequent in a dysexecutive AD subgroup compared with an amnestic AD subgroup [11]
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