J Stroke.  2025 Jan;27(1):65-74. 10.5853/jos.2024.02376.

Differentiating Cerebral Amyloid Angiopathy From Alzheimer’s Disease Using Dual Amyloid and Tau Positron Emission Tomography

• Tsai HH
• Pasi M
• Liu CJ
• Tsai YC
• Yen RF
• Chen YF
• Jeng JS
• Tsai LK
• Charidimou A
• Baron JC

• KMID: 2564263
• DOI: http://doi.org/10.5853/jos.2024.02376

Abstract

Background and Purpose
Although amyloid positron emission tomography (PET) might provide a molecular diagnosis for cerebral amyloid angiopathy (CAA), it does not have sufficient specificity for this condition relative to incipient Alzheimer’s disease (AD). To identify a regional amyloid uptake pattern specific to CAA, we attempted to reduce this overlap by selecting “pure CAA” (i.e., fulfilling the criteria for probable CAA but without tau PET AD signature) and “pure AD” (i.e., positive amyloid PET and presence of tau PET AD signature, but without lobar hemorrhagic lesions). We hypothesized that occipital tracer uptake relative to the whole cortex (WC) would be higher in patients with pure CAA and may serve as a specific diagnostic marker.
Methods
Patients who fulfilled these criteria were identified. In addition to the occipital region of interest (ROI), we assessed the frontal and posterior cingulate cortex (PCC) ROIs that are sensitive to AD. Amyloid PET uptake was expressed as the absolute standardized uptake value ratio (SUVR) and ROI/WC ratio. The diagnostic utility of amyloid PET was assessed using the Youden index cutoff.
Results
Eighteen patients with AD and 42 patients with CAAs of comparable age were eligible. The occipital/WC was significantly higher in CAA than AD (1.02 [0.97–1.06] vs. 0.95 [0.87–1.01], P=0.001), with an area under curve of 0.762 (95% confidence interval [CI] 0.635–0.889) and a specificity of 72.2% (95% CI 46.5–90.3) at Youden cutoff (0.98). The occipital lobe, frontal lobe, PCC and WC SUVRs were significantly lower in CAA than in AD. The frontal/WC and PCC/WC ratios did not differ significantly between the groups.
Conclusion
Using stringent patient selection to minimize between-condition overlap, this study demonstrated the specificity of higher relative occipital amyloid uptake in CAA than in AD.

Keyword

Cerebral amyloid angiopathy; Alzheimer disease; Positron emission tomography

Figure

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  Figure 1. Representative MRI, amyloid and tau scans in CAA and AD. (A) A patient with probable “pure” CAA with numerous lobar cerebral microbleeds but negative tau PET scan. (B) A patient with “pure” AD with positive amyloid and AD-signature tau PET scans. No lobar hemorrhagic lesions were found on SWI. MRI, magnetic resonance imaging; SWI, susceptibility-weighted imaging; PiB, Pittsburgh compound B; PET, positron emission tomography; CAA, cerebral amyloid angiopathy; AD, Alzheimer’s disease.

• 

  Figure 2. Comparisons of amyloid PET uptake in the occipital cortex and whole cortex. Box plots show (A) relative amyloid uptake in the occipital cortex (occipital/ whole cortex ratio), (B) absolute amyloid burden in the occipital cortex, and (C) absolute amyloid burden in the whole cortex. SUVR, standardized uptake value ratio; AD, Alzheimer’s disease; CAA, cerebral amyloid angiopathy; PET, positron emission tomography. *P<0.05.

Reference

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