DISTINGUISHING NON-AMNESTIC FROM AMNESTIC VARIANTS OF EARLY-ONSET ALZHEIMER’S DISEASE ON NEUROPSYCHOLOGICAL TESTS

Abstract

Patients with early-onset Alzheimer's disease (AD) include those with typical amnestic AD and those with atypical, non-amnestic presentations, including language, visuospatial, or executive disturbances, who have more focal neocortical localization early in the disease. There are no neuropsychological profiles to distinguish these non-amnestic variants as a group from typical amnestic presentations. We compared neuropsychological measures of 41 patients meeting AA-NIA criteria for AD and having an age of onset of <65 years of age. Based on the initial extensive physician clinical evaluation, these 41 patients were divided into amnestic (n=22 including 14 male/8 female; mean years for age-58.4, disease duration-3.2, education-16.1 years) vs. non-amnestic (n=19 including 8 male/11 female; mean years for age-59.7, disease duration-4.0, education-16.2). The two patient groups were of comparable severity on functional measures and had fluorodeoxyglucose positron emission tomography (FDG-PET) or cerebrospinal fluid biomarker confirmation of their disease. We then analyzed neuropsychological differences between these two groups. Six measures emerged as having either sensitivities of ≥0.8 or specificities of ≥0.9 for typical amnestic vs. non-amnestic AD (See Table 1). The amnestic EOAD patients were worse on the California Verbal Learning Test (CVLT) delayed recall scores, including “Savings Score” (free long-delayed recall/last registration trial) especially because of better memory registration and had many more false positives on CVLT recognition memory testing. In comparison, the non-amnestic AD patients were worse on Forward Digit Span, Trailmaking B time, Boston Naming Test (uncued), CVLT memory registration, and the Southern California Figure-Ground Test. 17 of the 19 non-amnestic EOAD patients were abnormal on all 6 tests, and the Trailmaking B added the highest specificity at 0.92. These results reveal significantly different neuropsychological profiles for the non-amnestic variants of AD, as a group, from typical AD. The findings suggest neuropsychological measure for differentiation of these variants that including measures of early impairment in mental control and executive abilities, uncued naming, memory registration, and mid-level visuospatial processing.