Year: 2014
Type: article
Study design: Observational Study
Abstract: A subset of clinically normal (CN) individuals has biomarker evidence of amyloidosis and/or neurodegeneration. Whether subtle cognitive changes are associated with these biomarker stages remains to be elucidated. We sought to determine if baseline cognitive profiles of CN subjects differ between biomarker negative subjects (Stage 0); amyloidosis alone (Stage 1); amyloidosis plus neurodegeneration (Stage 2) and neurodegeneration alone (SNAP). 158 CN subjects (CDR=0, MMSE >25; LMIIa >7) enrolled in the Harvard Aging Brain Study underwent neuropsychological testing, APOE genotyping, positron emission tomography (PiB-PET and FDG-PET) and magnetic resonance imaging. Amyloid status was determined with PiB-PET. Neurodegeneration was measured using two a priori imaging markers: MRI hippocampal volume and FDG-PET metabolism extracted from AD-vulnerable regions. Subjects were classified into 4 groups: Stage 0 (n=76, mean age=71.0 ± 4.8; 14.5% APOE4); Stage 1 (n=20, mean age=73.8 ± 5.3; 50.0% APOE4); Stage 2 (n=26, mean age=76.5 ± 6.3; 42.9% APOE4) and SNAP (n=36, mean age=76.9 ± 6.2; 12.9% APOE4). A Multivariate General Linear Model controlling for age and APOE4 status explored cognitive test performances between groups. Pairwise comparisons revealed that Stage 1 performed significantly worse than Stage 0 on challenging tests of memory for names (FNAME p=0.042) and occupations (FNAME p=0.033), 2 nd list learning on the Memory Capacity Test (MCT DR, p=0.017), executive function (working memory WM, p=0.016; Letter Number Sequencing LNSq , p=0.027) and naming (BNT p=0.026). Stage 2 performed significantly worse than Stage 0 on more standard memory tests such as the Free and Cued Selective Reminding Test (FRsrt p=0.015; FCsrt p=0.010) and worse than Stage 1 on challenging memory (MCT IR p=0.029, MCT DR p=0.009 and MCT CR p=0.002) and executive function tests (LNSq p=0.001, Trails A p=0.034 and WM p=0.042). SNAP performed similar to Stage 0 on standard and challenging memory tests but worse on executive tests (fluency, p=0.031, WM p=0.012, and LNSq p=0.030). These findings suggest that subtle cognitive changes are associated with different biomarker stages in CN older adults.Amyloidosis is associated with impairment on both challenging memory and executive tests. Neurodegeneration is associated with more executive dysfunction than memory. The combination of amyloidosis and neurodegeneration results in more significant decline in memory and executive performance.
Source: Alzheimer s & Dementia
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2097152254