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Semi‐quantitative [ 11 C]PiB and [ 15 O]H 2 O PET measures of cerebrospinal fluid dynamics discriminate amyloid load but not cognitive status
Author(s) -
Minhas Davneet S,
Laymon Charles M,
Lopresti Brian J,
Cohen Ann D,
Tudorascu Dana L,
Mason Neale S,
Lopez Oscar L.,
Villemagne Victor L,
Aizenstein Howard J,
Mathis Chester A,
Klunk William E
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.055716
Subject(s) - cerebrospinal fluid , pittsburgh compound b , cognitive impairment , ventricle , medicine , nuclear medicine , cerebellum , pathology , psychology , disease
Background Altered interstitial and cerebrospinal fluid (CSF) dynamics have been linked to impaired amyloid clearance in animal models of Alzheimer’s disease (AD). Recent dynamic PET studies using tau and amyloid PET tracers [ 18 F]THK5117 and [ 11 C]PiB have sought to quantify CSF dynamics in humans [de Leon 2017, Schubert 2019]. The aim of this work was to examine the relationships between [ 11 C]PiB and [ 15 O]H 2 O semi‐quantitative measures of CSF dynamics, efflux and influx, respectively; amyloid load; and cognitive status. Method Nineteen participants consisting of n=5 cognitively normal (CN; 71.6±8.9 years, 3 female), 9 mild cognitive impairment (MCI; 68.6±9.9 years, 2 female), and 5 Alzheimer’s disease (AD; 67.0±9.0 years, 0 female) subjects underwent [ 11 C]PiB PET (0‐90min post‐injection, 34 frames), [ 15 O]H 2 O PET (0‐3min post‐injection, 20 frames), and 1.5T T1 MR imaging. MR images were processed using FreeSurfer 7.1 (FS). Amyloid load status (PiB‐/+) was assessed using a FS Global [ 11 C]PiB 50‐70min SUVR (cerebellar gray matter [GM] reference) and a cutoff of 1.35 SUVR. FS lateral ventricle ROIs were eroded using a 5mm kernel to minimize partial volume contamination from neighboring tissue and used to calculate three semi‐quantitative ventricular CSF outcomes: [ 11 C]PiB ventricular SUVR 50‐70 (cerebellar GM reference), [ 11 C]PiB ventricular AUC 35‐90 (cerebellar GM reference), and [ 15 O]H 2 O ventricular influx ratio (IR; 1.0‐3.0min, whole brain reference). Relationships between PET outcomes were assessed using Spearman’s correlations, and group differences across cognitive and amyloid statuses were assessed using the Mann‐Whitney U test. Result Eleven subjects were classified as PiB+ (1/5 CN, 5/9 MCI, 5/5 AD). Both [ 11 C]PiB ventricular outcomes were significantly correlated with [ 15 O]H 2 O IR ([ 11 C]PiB SUVR 50‐70 p<0.001; [ 11 C]PiB AUC 35‐90 p<0.001). In this population, no significant differences were observed across any pair of diagnostic groups for any of the three ventricular outcome measures (Figure 1). However, significant differences were observed between PiB‐ and PiB+ groups across all three ventricular CSF outcomes (Figure 2; [ 11 C]PiB SUVR 50‐70 p=0.033; [ 11 C]PiB AUC 35‐90 p=0.041; [ 15 O]H 2 O IR p=0.001). Conclusion The results observed in this population suggest CSF dynamics are altered early in the AD pathophysiological spectrum and are associated with amyloid load. In addition, ventricular CSF dynamics measured using [ 15 O]H 2 O IR provided greater discriminatory power than [ 11 C]PiB CSF outcomes.