Leuko-araiosis and cerebral perfusion in normal aging

Abstract

To clarify the incidence, age relationships and pathogenesis of white matter lesions of unknown origin (leuko-araiosis) detected by neuroimaging among normal elderly volunteers, we measured the severity of leuko-araiosis using computerized tomographic (CT) densitometry among 42 healthy self-supporting men and women of different ages, all with normal neurological and cognitive test performance. Results were correlated with local cerebral perfusion using xenon-contrasted CT. The 42 volunteers, who are followed in this laboratory for studies of normal aging, were divided into two groups in order to determine aging effects by an extremes design. One group consisted of 19 adults below age 60 (M = 53.3, SD = 6.0). The index group comprised 23 individuals all over the age of 60 (M = 71.6, SD = 8.7). Leuko-araiosis around the anterior horns of the lateral ventricles (frontal leuko-araiosis) was more severe (p < .01) among the older group, however, occipital leuko-araiosis did not significantly differ between older and younger groups. Cerebral perfusion in frontal, temporal, and parietal cortex was decreased among older compared with younger volunteers (ps < .001, .01, and .05, respectively). Multiple regression analyses disclosed significant and direct relationships between severity of frontal leuko-araiosis and (a) frontal cortical atrophy and (b) reductions of cerebral perfusion within frontal white matter and caudate nucleus. We conclude that cortical atrophy with hypoperfusion and ischemia of frontal white matter play a part in the pathogenesis of frontal leuko-araiosis associated with normal aging and this may be a predictor for later cognitive declines.

Neuroinflammation in healthy aging: A PET study using a novel Translocator Protein 18kDa (TSPO) radioligand, [18F]-FEPPA

“…Age-associated reduction in blood flow is well documented (Iwata and Harano, 1986; Schultz et al, 1999; Takahashi et al, 2005). However, the correlation between age and cerebral hypoperfusion is stronger in individuals with vascular risk factors (de la Torre, 2012; Fazekas et al, 1988; Kawamura et al, 1993). In the present study, we only included healthy individuals who had no history of past cardiovascular events.…”

Use of Functional Magnetic Resonance Imaging in the Early Identification of Alzheimer's Disease

“…For example, there is growing evidence that changes in the cerebrovascular system due to age and disease can significantly alter the BOLD signal and complicate its interpretation (D'Esposito et al, 2003). Age-related factors include altered cerebrovascular ultrastructure, reduced elasticity of vessels, increased atherosclerosis, reduced resting state CBF, decreased resting CMRO 2 , and reduced vascular reactivity to chemical modulators (Bentourkia et al, 2000;Claus et al, 1998;D'Esposito et al, 2003;Kawamura et al, 1993;Markus et al, 2001;Takada et al, 1992;Yamaguchi et al, 1986;Yamamoto et al, 1980). In fMRI studies of the effects of aging, researchers have found a significant age-related decrease in the BOLD signal amplitude (Buckner et al, 2000;Gopinath et al, 2006;Tekes et al, 2005), possibly reflecting age-related decreases in the elasticity of the cerebrovascular system (D'Esposito et al, 2003;Uspenskaia et al, 2004).…”

Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging

“…In the brain, the number of endothelial cells is very similar to that of neurons (GarciaAmado and Prensa 2012) and nearly every neuron is supplied by its own capillary, with an average distance of 8-20 μm between the neuron and the microvessels. Importantly, there is strong evidence that aging is associated with a decline in cerebral capillary density ("microvascular rarefaction") and that decreases in cerebromicrovascular density contribute to the agerelated decline in regional cerebral blood flow (Mitschelen et al 2009;Riddle et al 2003;Khan et al 2001;Lynch et al 1999;Sonntag et al 1997;Martin et al 1991;Moeller et al 1996;Farkas and Luiten 2001;Kawamura et al 1993;Krejza et al 1999;Schultz et al 1999;Bentourkia et al 2000;Hagstadius and Risberg 1989;Pagani et al 2002). The resulting mismatch between energy supply and demand has been causally linked to significant cognitive impairment (reviewed in Sonntag et al 1997;Ingraham et al 2008;Sonntag et al 2000;Warrington et al 2011;Warrington et al 2012).…”