Hippocampal hyperperfusion in Alzheimer's disease

Abstract

Many of the regions with the earliest atrophy in Alzheimer's Disease (AD) do not show prominent deficits on functional imaging studies of flow or metabolism. This paradox may provide unique insights into the pathophysiology of AD. We sought to examine the relationship between function and atrophy in AD using MRI blood flow and anatomic imaging. 22 subjects diagnosed with AD, mean Mini Mental State Exam (MMSE) score 22.2, and 16 healthy elderly controls were imaged with a volumetric arterial spin labeling blood flow MRI technique and an anatomical imaging method using the identical spatial resolution, image orientation, and spatial encoding strategy. Cerebral blood flow(CBF) and gray matter (GM) maps derived from the imaging were transformed to a standard anatomical space. GM and CBF maps were tested for significant differences between groups. Additionally, images were tested for regions with significant mismatch of the CBF and GM differences between groups. CBF was significantly lower in the bilateral precuneus, parietal association cortex and the left inferior temporal lobe but was non-significantly increased in the hippocampus and other medial temporal structures. After correction for GM loss, CBF was significantly elevated in the hippocampus and other medial temporal structures. The hippocampus and other regions affected early in AD are characterized by elevated atrophy-corrected perfusion per cc of tissue. This suggests compensatory or pathological elevation of neural activity, inflammation, or elevated production of vasodilators.

Distinct cerebral perfusion patterns in FTLD and AD

“…Cross-sectional studies thus have suggested that patients with very mild AD and mild cognitive impairment (MCI) may have hippocampal hyperperfusion. 32,33 This would be consistent with other work showing increased medial temporal activation during performance of memoryrelated tasks in MCI 35 and hippocampal neuronal hypertrophy in asymptomatic AD. 36 One longitudinal study related hippocampal activation to subsequent cognitive decline in AD.…”

“…18 The latter step was reported in a study that found more significant hyperperfusion in hippocampus in patients with mild AD after correction. 23 However, similar effects but with a slightly reduced significance level were obtained if the second Jacobian-based correction was not applied. Accordingly, the observed hypoperfusion likely reflects functional changes beyond those that can be attributed to atrophy alone.…”

“…30 Cortical hyperperfusion has been described in several previous studies. 32,33 This may be related in part to a similar mechanism implicated in the neuronal hypertrophy observed in the anterior cingulate of asymptomatic AD. 36 We also cannot rule out the contribution of partial deafferentation due to degraded WM projections from diseased areas.…”

“…The volume changes caused by the transformation were corrected using the modulation option in the DARTEL package to adjust CBF signal in areas that were compressed or expanded during image normalization. 18,23 The peak of each suprathreshold cluster was identified. The local template was mapped into Montreal Neurological Institute (MNI) space, and the same transformation was used to transfer the coordinates of these peaks into MNI space.…”

Arterial hypertension impact on cerebral blood flow in patients with Alzheimer’s disease

“…Other studies have paradoxically showed that early on, cerebral blood flow is increased in the hippocampus and other regions in Alzheimer patients. 6 Various clinical, epidemiological and pathological studies suggest that AD is more frequently associated with stroke than expected; vascular brain lesions and those connected with AD are often related; β-amyloid plaques are more abundant in non-demented patients who have died from coronary artery disease than in those who have died from other causes. These findings suggest that vascular pathology and AD are directly related or at least share common determinants.…”