Hypoperfusion and Ischemia in Cerebral Amyloid Angiopathy Documented by ^99mTc-ECD Brain Perfusion SPECT

Abstract

Cerebral amyloid angiopathy (CAA) is known to be an important cause of spontaneous cortical-subcortical intracranial hemorrhage in normotensive older persons. CAA can also manifest as leukoencephalopathy, brain atrophy, and ischemia secondary to hypoperfusion. Our goal was to verify cerebral hypoperfusion in patients with CAA using 99m Tc-ethylcysteinate dimer ( 99m Tc-ECD) brain perfusion SPECT. Methods: A total of 11 patients (5 men and 6 women; age range, 58-78 y; mean age 6 SD, 70.0 6 7.0 y) with clinically and radiologically established probable CAA who underwent 99m Tc-ECD SPECT were included. 99m Tc-ECD SPECT scans were also obtained from 13 agematched healthy control subjects (7 men and 6 women; age range, 60-79 y; mean age 6 SD, 66.7 6 6.4 y) for comparison. The relative regional cerebral blood flow values obtained for patients and controls were compared using software. Results: Compared with controls, patients with probable CAA showed hypoperfusion in the inferior parietal lobule of both parietal lobes (Brodmann area [BA] 40), middle temporal gyrus of the left temporal lobe (BA 39), postcentral gyrus of the right parietal lobe, superior temporal gyrus of the right temporal lobe (BA 22), superior temporal gyrus of the right frontal lobe (BA 10), inferior temporal gyrus of the left temporal lobe (BA 20), and both caudate bodies (P , 0.0001, t 5 4.65). Conclusion: Patients with probable CAA had significantly decreased cerebral perfusion and may be at risk for leukoencephalopathy, atrophy, and ischemia.

Cerebral vascular amyloid seeds drive amyloid β-protein fibril assembly with a distinct anti-parallel structure

“…Cerebral vascular amyloid can contribute to cognitive decline in AD and familial forms of CAA by promoting several pathological consequences including neuroinflammation1213, chronic hypoperfusion and ischemia1415, and, in severe cases, loss of vessel wall integrity and haemorrhage1617. Further, studies have reported that cerebral microvascular Aβ deposition is more often correlated with dementia in individuals afflicted with AD and spontaneous CAA disorders418.…”

Regional cerebral blood flow estimated by early PiB uptake is reduced in mild cognitive impairment and associated with age in an amyloid-dependent manner

“…Reductions in CBF with older age in PiB-positive subjects could be caused by a decreasing vascular reserve (Brown and Thore, 2011) or the influence of vascular amyloid deposition (cerebral amyloid angiopathy) that has been implied by pathologic (Thal et al, 2008) and imaging studies in humans (Chung et al, 2009;Peca et al, 2013) and in animal studies (Merlini et al, 2011). A recent article showed that transgenic APP23 mice that are prone to develop plaques and cerebral amyloid angiopathy (Maier et al, 2014) display a loss of cerebral perfusion with increasing age and disease progression, whereas nontransgenic litter maids did not display any change in rCBF.…”

The Cerebrovascular Basement Membrane: Role in the Clearance of β-amyloid and Cerebral Amyloid Angiopathy

“…CAA is associated with capillary thinning and vessel tortuosity, inhibition of angiogenesis, and the death of pericytes, endothelial, and smooth muscle cells (Perlmutter et al, 1994; Miao et al, 2005; Haglund et al, 2006; Tian et al, 2006; Burger et al, 2009). Cerebral hypoperfusion, microhemorrhages, and cognitive impairment have also been shown to be associated with CAA severity (Natte et al, 2001; Pfeifer et al, 2002a,b; Shin et al, 2007; Chung et al, 2009). …”