Person:

Dickerson, Bradford

Introduction: One major factor that influences the heterogeneity of Alzheimer's disease (AD) is age: younger AD patients more frequently exhibit atypical forms of AD. We propose that this age-related heterogeneity can be understood better by considering age-related differences in atrophy in the context of large-scale brain networks subserving cognitive functions that contribute to memory. Methods: We examined data from 75 patients with mild AD dementia from Alzheimer's Disease Neuroimaging Initiative. These individuals were chosen because they have cerebrospinal fluid amyloid and p-tau levels in the range suggesting the presence of AD neuropathology, and because they were either younger than age 65 years early-onset AD (EOAD) or age 80 years or older late-onset AD (LOAD). Results: In the EOAD group, the most prominent atrophy was present in the posterior cingulate cortex, whereas in the LOAD group, atrophy was most prominent in the medial temporal lobe. Structural covariance analysis showed that the magnitude of atrophy in these epicenters is strongly correlated with a distributed atrophy pattern similar to distinct intrinsic connectivity networks in the healthy brain. An examination of memory performance in EOAD dementia versus LOAD dementia demonstrated relatively more prominent impairment in encoding in the EOAD group than in the LOAD group, with similar performance in memory storage in LOAD and EOAD but greater impairment in semantic memory in LOAD than in EOAD. Discussion The observations provide novel insights about age as a major factor contributing to the heterogeneity in the topography of AD-related cortical atrophy.

Background: Hypertension is the strongest modifiable risk factor for subcortical ischemic changes and is also a risk factor for Alzheimer’s dementia. We used neuroimaging to investigate the pathological basis of early cognitive symptoms in patients with hypertension. Methods: In this cross-sectional cohort study 67 patients age >60 years with hypertension and Clinical Dementia Rating scale score of 0.5 without dementia, and without history of symptomatic stroke, underwent MRI for measurement of subcortical vascular changes and positron emission tomography (PET) scan with Pittsburgh Compound B (PiB-PET) to detect beta-amyloid deposition. These imaging measures were related to neuropsychological tests of memory, executive function and processing speed. Results: Mean age was 75.0 (standard deviation, SD, 7.3). Mean neuropsychological Z scores were: episodic memory -0.63 (SD 1.23), executive function -0.40 (SD 1.10), processing speed -0.24 (SD 0.88); 22 of the 67 subjects met criteria for mild cognitive impairment (MCI) and the remaining 45 subjects had subjective cognitive concerns only. In multivariable models adjusting for age and years of education, each 0.1 unit increase in mean cortical PiB-PET binding was associated with 0.14 lower mean Z score for episodic memory (95% CI -0.28 to -0.01). This means that for every 0.1 unit increase in mean cortical PiB-PET, episodic memory was 0.14 standard deviations lower. White matter hyperintensity volume, silent brain infarcts and microbleeds were not associated with neuropsychological test scores. Conclusions: Episodic memory was prominently affected in hypertensive participants with MCI or subjective cognitive concerns, and was associated with PiB-PET binding. This suggests a prominent role for Alzheimer pathology in cognitive impairment even in hypertensive participants at elevated risk for vascular cognitive impairment.