We read with great interest the article by Klinger et al. regarding the cerebral β-amyloid deposition and neurocognitive performance after cardiac surgery.1  We congratulate them for their excellent work in exploring the etiology and pathology of postoperative cognitive dysfunction. This study demonstrated no significant correlations between β-amyloid deposition and cognitive function at several time points after cardiac surgery. However, we want to address several points regarding this study.

First, we cannot draw any definite conclusions based on this study regarding the correlation between cerebral β-amyloid deposition and neurocognitive performance after cardiac surgery. Postoperative cognitive dysfunction is a multifactorial disease with complicated etiology and pathology. An appropriate subject sample size was needed for exploring one unproved factor influencing this disease. However, this study included only seven or two samples of abnormal β-amyloid deposition burden at 6 weeks or 1 yr after cardiac surgery, respectively. Analyzing postoperative cognitive dysfunction incidence in these samples could not provide a definite conclusion. In fact, it would make more sense to analyze postoperative cognitive dysfunction incidence in subjects with normal amyloid deposition because of their larger sample size (n = 33 or 10 at 6 weeks or 1 yr, respectively).

Second, neuroimaging was mostly performed 6 weeks after surgery in this study after considering the funding constraints and benefits of patients. However, we doubt whether the choice of this time point is accurate. We prefer that neuroimaging should have been performed before surgery as a baseline neuroimaging scan. On one hand, the authors scheduled the brain imaging after 6 weeks based on Landau et al.’s study,2  which showed that amyloid burden was not expected to change significantly over a 6-week time. However, Landau’s study evaluated the change in cortical 18F-florbetapir over a 2-yr period in several candidate cerebral regions of interest in nonsurgical participants. It did not provide any evidence about the influence of surgery on cerebral amyloid change at 6 weeks or later. On the other hand, analyzing preoperative amyloid uptake ratio with postoperative cognitive dysfunction rate could be interpreted as a potential predictive factor for postoperative cognitive dysfunction if they were correlated with each other.

Third, a recent study suggests that β-amyloid turnover rates decreased dramatically with age, which increased the likelihood of amyloid deposition,3  and the accumulation of β-amyloid in the brain was related to long-term cognitive impairment.4  Paradoxically, postoperative cognitive dysfunction often occurs immediately after surgery, recovers over time, and rarely persists in the longer term.5  Thus, the underlying relationship between them could be unforeseen. Three problems that were not emphasized in this study were rather important: the association of preoperative amyloid status of patients with long-term postoperative cognitive dysfunction, the impact of major surgery and anesthesia on amyloid burden, and the association of amyloid deposition in cerebral nuclei with cognitive impairment.

In summary, this study by Klinger et al.1  was a great work employing amyloid imaging to investigate the association of evolving brain amyloid burden with postoperative cognitive dysfunction in patients undergoing cardiac surgery. Although it is not convincing enough because of the sample size and study design, it supports further investigations of etiologic mechanisms underlying postoperative cognitive dysfunction because the data on this field is scarce.

Supported by the National Natural Science Foundation of China (Beijing, China; grant No. 81571048).

The authors declare no competing interests.

1.
Klinger
RY
,
James
OG
,
Borges-Neto
S
,
Bisanar
T
,
Li
YJ
,
Qi
W
,
Berger
M
,
Terrando
N
,
Newman
MF
,
Doraiswamy
PM
,
Mathew
JP
;
Alzheimer’s Disease Neuroimaging Initiative (ADNI) Study Group; Neurologic Outcomes Research Group (NORG)
:
18F-florbetapir positron emission tomography-determined cerebral β-amyloid deposition and neurocognitive performance after cardiac surgery.
Anesthesiology
2018
;
128
:
728
44
.
2.
Landau
SM
,
Fero
A
,
Baker
SL
,
Koeppe
R
,
Mintun
M
,
Chen
K
,
Reiman
EM
,
Jagust
WJ
:
Measurement of longitudinal β-amyloid change with 18F-florbetapir PET and standardized uptake value ratios.
J Nucl Med
2015
;
56
:
567
74
.
3.
Patterson
BW
,
Elbert
DL
,
Mawuenyega
KG
,
Kasten
T
,
Ovod
V
,
Ma
S
,
Xiong
C
,
Chott
R
,
Yarasheski
K
,
Sigurdson
W
,
Zhang
L
,
Goate
A
,
Benzinger
T
,
Morris
JC
,
Holtzman
D
,
Bateman
RJ
:
Age and amyloid effects on human central nervous system amyloid-beta kinetics.
Ann Neurol
2015
;
78
:
439
53
.
4.
Hatashita
S
,
Wakebe
D
:
Amyloid-β deposition and long-term progression in mild cognitive impairment due to Alzheimer’s disease defined with amyloid PET imaging.
J Alzheimers Dis
2017
;
57
:
765
73
.
5.
Needham
MJ
,
Webb
CE
,
Bryden
DC
:
Postoperative cognitive dysfunction and dementia: What we need to know and do.
Br J Anaesth
2017
;
119
(
suppl_1
):
i115
25
.