Abstract
Recently, imaging biomarkers have gained importance for the characterization of patients with Alzheimer’s disease; however, the relationship between regional biomarker expression and cognitive function remains unclear. In our study, we investigated associations between scores on CERAD neuropsychological assessment battery (CERAD-NAB) subtests with regional glucose metabolism, cortical thickness and amyloid deposition in patients with early Alzheimer’s disease (AD) using [18F]-fluorodeoxyglucose (FDG), structural MRI, and 11C-Pittsburgh Compound B (PiB) positron emission tomography (PET), respectively. A total of 76 patients (mean age 68.4 ± 8.5 years, 57.9% male) with early AD (median global clinical dementia rating (CDR) score = 0.5, range: 0.5–2.0) were studied. Associations were investigated by correlation and multiple regression analyses. Scores on cognitive subtests were most closely predicted by regional glucose metabolism with explained variance up to a corrected R² of 0.518, followed by cortical thickness and amyloid deposition. Prediction of cognitive subtest performance was increased up to a corrected R² of 0.622 for Word List—Delayed Recall, when biomarker information from multiple regions and multiple modalities were included. For verbal, visuoconstructive and mnestic domains the closest associations with FDG-PET imaging were found in the left lateral temporal lobe, right parietal lobe, and posterior cingulate cortex, respectively. Decreased cortical thickness in parietal regions was most predictive of impaired subtest performance. Remarkably, cerebral amyloid deposition significantly predicted cognitive function in about half of the subtests but with smaller extent of variance explained (corrected R² ≤ 0.220). We conclude that brain metabolism and atrophy affect cognitive performance in a regionally distinct way. Significant predictions of cognitive function by PiB-PET in half of CERAD-NAB subtests suggest functional relevance even in symptomatic patients with AD, challenging the concept of plateauing cortical amyloid deposition early in the disease course. Our results underscore the complex spatial relationship between different imaging biomarkers.
Highlights
Alzheimer’s disease (AD) is the most common cause for dementia and its prevalence continues to rise in ageing societies [1]
We have systematically investigated the relationship between cognitive performance and three cortical imaging biomarkers, namely cortical thickness, glucose metabolism, and amyloid deposition in a single, reasonably sized cohort of wellcharacterized early AD patients
We found that on a global level, only glucose metabolism but not cortical atrophy or cortical amyloid deposition was correlated with CERAD-neuropsychological assessment battery (NAB) subtest results
Summary
Alzheimer’s disease (AD) is the most common cause for dementia and its prevalence continues to rise in ageing societies [1]. In vivo characterization of corresponding imaging biomarkers have been strengthened in a currently published research framework [5] Another hallmark of AD is decline in different cognitive domains, which is typically assessed by standardized neuropsychological testing [6]. One of the most widely used procedures is the neuropsychological assessment battery (NAB) of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) [7]. This neuropsychological assessment covers both general cognitive ability—as determined by the short tests incorporated in the Mini-Mental State examination (MMSE)—and certain cognitive domains such as verbal and non-verbal episodic memory, visuoconstructive capacities, semantic fluency, and executive functions [6, 8]
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