B

Figure 35.8 3-dimensional rendering of brain regions showing a significant age-related reduction in gray (A) and white matter (B) brain regions. Regional atrophy for males and females is shown in green and red, respectively. Areas of overlap for old males and females are shown in yellow. Brain renderings are presented in saggital and axial orientations. (Abbreviations: FL = frontal lobe, PL = parietal lobe, TL = temporal lobe, CB = cerebellum, IC = internal Capsula, AVH = alveus of the hippocampus, OpN = optic nerve bundle, IC/Hyp = internal capsula/hypophysis.) See the color plate section.

Figure 35.9 Coronal Tl-weighted MRI slices presented rostrocaudally displaying two types of lesions in the aged dog brain: small (less than 1 cm diameter) lacunes (solid arrow-line) and large (greater than 1 cm diameter) infarcts (broken arrow-line).

the frontal lobes are especially vulnerable to aging in the dog (Head et al., 1998; Tapp et al., 2004a).

Cerebrovascular changes in the aging dog brain MRI is also used to assess hemodynamic changes in the dog by combining high-resolution MRI and paramagnetic intravascular susceptibility contrast agents (e.g., Gd-DTPA) to derive measures of cerebrovascular volume, flow, and blood-brain barrier integrity. In humans, dynamic susceptibility contrast enhanced (DSC)-MRI is sensitive to decreases in blood volume in temporoparietal brain regions in AD and MCI patients relative to healthy age-matched controls (Harris et al., 1998). In a study of 18 dogs aged 4-15 years of age, a significant correlation was found between blood-brain barrier (BBB) permeability, beta-amyloid deposition, and ventricular dilation (Su et al., 1998). Further, this increased BBB leakage occurred in the absence of cortical atrophy, suggesting that changes in BBB integrity precede cortical atrophy and may be an early consequence of aging.

Reduced blood flow and volume are frequently associated with age-related cognitive decline in humans. DSC-MRI studies performed in dogs have illustrated that impaired hemodynamics also contribute to brain aging (Tapp et al., 2005a). First, gray matter regional cerebral blood volume (rCBV) was consistently higher than white matter rCBV in young and old dogs. Second, gray and white matter rCBV declined with age. Third, age-related changes in rCBV were largest in white matter brain regions compared to gray matter brain regions. Moreover, decreased rCBV and increased BBB permeability occurred in tandem with regional gray and white matter cortical atrophy.

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