[This study] adds to a growing literature that reframes and shifts the discussion about causation of post operative cognitive decline from intra- and postoperative variables to the preoperative state of the patient.

Image: ©Thinkstock.

Image: ©Thinkstock.

BEFORE there was postoperative cognitive dysfunction (POCD), there was “pump head.” The latter is a syndrome of cognitive decline after cardiac surgery that is well recognized by clinicians and feared by patients. There is no doubt it happens. A landmark study 15 yr ago showed that over 40% of patients were cognitively impaired 5 yr after coronary artery bypass graft (CABG) surgery,1  results subsequently confirmed by others. Pump head is analogous to POCD; it is not dementia, but naturally there is concern one may lead to, or predict, the other. This is where it gets messy. Patients needing CABG surgery have cardiovascular disease, and cardiovascular disease is a well-established risk factor for cognitive impairment and dementia irrespective of surgery.2  In fact, patients with coronary artery disease managed medically or with a percutaneous procedure have the same prevalence of cognitive decline 6 yr later as those who have on-pump CABG surgery.3,4  This suggests that “pump head” is likely a misnomer and that preexisting cardiovascular disease is the main driver of cognitive decline in these patients. But does CABG surgery push patients slowly over the edge to full-blown dementia? That’s the important question addressed by Evered et al.5  in this issue of Anesthesiology.

Evered et al. asked whether CABG surgery is associated with the development of POCD and dementia, and whether the former is associated with the latter. They recruited patients at a 12-month follow-up appointment from a study designed and powered to evaluate differences in POCD between high- and low-dose fentanyl for cardiac surgery6  and followed them for another 6.5 yr. They classified preexisting cognitive impairment (PreCI), POCD by a standard test battery, and dementia by the clinical dementia rating scale and review of all cognitive and functional data. The main result paints a relatively bleak picture of long-term cognitive outcome among CABG surgery patients: about one in three patients were demented (30.8%) or had POCD (32.8%) 7.5 yr after surgery. However, while POCD was associated with higher mortality, a result that confirms studies involving noncardiac surgery,7,8  it did not predict dementia. In fact, of the subset (N = 113) evaluated for both, only 44% with dementia satisfied criteria for POCD. What did predict dementia was nonsurgery/anesthesia factors, specifically, peripheral vascular disease and PreCI.5  Thus, the work of Evered et al. suggests that disease burden and the state of cognition before surgery, not the surgery itself, are the main drivers of cognitive outcome after.

This is a significant contribution because there are no other prospective studies of cognitive outcomes of surgery and anesthesia that can boast of such long-term follow-up. Still, the results should be interpreted cautiously. First, the control group did not have cardiovascular disease or surgery, and there was no control for coronary artery disease managed without CABG surgery. Consequently, one cannot resolve whether the POCD (and mortality) was related to the surgery or the vascular disease. Also, as noted by the authors, lack of a baseline dementia evaluation makes it difficult to attribute the higher prevalence of dementia in the study group to vascular disease versus surgery. Previous studies indicate that cardiac surgery does not accelerate cognitive decline,3,4  but none have used formally diagnosed dementia as the outcome. Second, only 35% of patients from the original study had follow-up for both POCD and dementia, meaning outcomes were not available for the majority and analyses were based on relatively small numbers in some of the categories. This is reflected in the wide CIs for PreCI and peripheral vascular disease as predictors of dementia, suggesting low validity and reproducibility of the univariable model. The absence of a multivariable analysis is another limitation, as it may have led to different conclusions. Finally, the loss to follow-up is an issue because, in studies of cognition, subjects who fail to complete testing are often those most likely to be impaired. As such, the study of Evered et al. may underestimate the prevalence of POCD, dementia, and the relationship between the two after CABG.

That said, the work of Evered et al. conveys a vital message: preoperative factors, especially cardiovascular disease and baseline cognition, may have more to do with postoperative cognitive outcome than anesthetic or surgical factors. That is not to say anesthesia and surgery are irrelevant, as some studies suggest otherwise,7,9  but rather that the impact of these and other perioperative events on cognition may vary widely depending on the preexisting state of the patient. We already know that preoperative coronary artery, pulmonary, and renal diseases influence postoperative outcomes, but much of the clinical research to date on postoperative cognition, and especially POCD in noncardiac surgery, has grouped patients by age and procedure but little else. As a result, study cohorts might unknowingly be quite heterogeneous with respect to risk variables, making associations between patient factors—anesthesia/surgery variables—and postoperative cognitive decline all the more obscure. Going forward, studies of postoperative cognitive decline should control for preoperative vascular disease, not just after the fact in the data analysis but prospectively by matching groups—including nonsurgical controls—for the presence and severity of such disease. Evered et al.’s observation that PreCI predicts post-CABG dementia is not surprising as, like vascular disease, cognitive impairment is a risk factor for dementia irrespective of surgery. It is also consistent with data from a recent study of twins that demonstrated preoperative cognition is more important than anesthesia or surgery in determining postoperative cognitive function.10  So, as we have argued previously,11  maybe it is time to institute routine preoperative cognitive screening for certain risk groups. Even among elective noncardiac surgery patients, about 30% of those over 65 yr of age screen positive.12  Whether a brief cognitive screen can provide the information necessary to predict postoperative cognitive complications or outcome, let alone equip us to do something about it, remains to be seen, but the work of Evered et al. suggests it is worth trying.

The study of Evered et al. adds to a growing literature that reframes and shifts the discussion about causation of postoperative cognitive decline from intra- and postoperative variables to the preoperative state of the patient. Although preexisting conditions are unlikely to be the whole story,13–15  this shift is overdue and welcome, for chief among the many things we do not know about cognitive outcomes of surgery is the influence of the patient.

Research Support

The authors are supported by grants from the Anesthesia Patient Safety Foundation (Indianapolis, Indiana) and CRICO (Boston, Massachusetts) (to Dr. Culley) and by grants AG048522 (to Dr. Culley) and AG048637 (to Dr. Crosby) from the National Institutes of Health (Bethesda, Maryland).

Competing Interests

The authors are not supported by, nor maintain any financial interest in, any commercial activity that may be associated with the topic of this article.

References

1.
Newman
MF
,
Kirchner
JL
,
Phillips-Bute
B
,
Gaver
V
,
Grocott
H
,
Jones
RH
,
Mark
DB
,
Reves
JG
,
Blumenthal
JA
;
Neurological Outcome Research Group and the Cardiothoracic Anesthesiology Research Endeavors Investigators
:
Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery.
N Engl J Med
2001
;
344
:
395
402
2.
Newman
AB
,
Fitzpatrick
AL
,
Lopez
O
,
Jackson
S
,
Lyketsos
C
,
Jagust
W
,
Ives
D
,
Dekosky
ST
,
Kuller
LH
:
Dementia and Alzheimer’s disease incidence in relationship to cardiovascular disease in the Cardiovascular Health Study cohort.
J Am Geriatr Soc
2005
;
53
:
1101
7
3.
Selnes
OA
,
Grega
MA
,
Bailey
MM
,
Pham
LD
,
Zeger
SL
,
Baumgartner
WA
,
McKhann
GM
:
Cognition 6 years after surgical or medical therapy for coronary artery disease.
Ann Neurol
2008
;
63
:
581
90
4.
Selnes
OA
,
Grega
MA
,
Bailey
MM
,
Pham
LD
,
Zeger
SL
,
Baumgartner
WA
,
McKhann
GM
:
Do management strategies for coronary artery disease influence 6-year cognitive outcomes?
Ann Thorac Surg
2009
;
88
:
445
54
5.
Evered
LA
,
Silbert
BS
,
Scott
DA
,
Maruff
P
,
Ames
D
:
Prevalence of dementia 7.5 years after coronary artery bypass graft surgery.
Anesthesiology
2016
;
125
:
62
71
6.
Silbert
BS
,
Scott
DA
,
Evered
LA
,
Lewis
MS
,
Kalpokas
M
,
Maruff
P
,
Myles
PS
,
Jamrozik
K
:
A comparison of the effect of high- and low-dose fentanyl on the incidence of postoperative cognitive dysfunction after coronary artery bypass surgery in the elderly.
Anesthesiology
2006
;
104
:
1137
45
7.
Monk
TG
,
Weldon
BC
,
Garvan
CW
,
Dede
DE
,
van der Aa
MT
,
Heilman
KM
,
Gravenstein
JS
:
Predictors of cognitive dysfunction after major noncardiac surgery.
Anesthesiology
2008
;
108
:
18
30
8.
Steinmetz
J
,
Christensen
KB
,
Lund
T
,
Lohse
N
,
Rasmussen
LS
;
ISPOCD Group
:
Long-term consequences of postoperative cognitive dysfunction.
Anesthesiology
2009
;
110
:
548
55
9.
Moller
JT
,
Cluitmans
P
,
Rasmussen
LS
,
Houx
P
,
Rasmussen
H
,
Canet
J
,
Rabbitt
P
,
Jolles
J
,
Larsen
K
,
Hanning
CD
,
Langeron
O
,
Johnson
T
,
Lauven
PM
,
Kristensen
PA
,
Biedler
A
,
van Beem
H
,
Fraidakis
O
,
Silverstein
JH
,
Beneken
JE
,
Gravenstein
JS
:
Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International study of post-operative cognitive dysfunction.
Lancet
1998
;
351
:
857
61
10.
Dokkedal
U
,
Hansen
TG
,
Rasmussen
LS
,
Mengel-From
J
,
Christensen
K
:
Cognitive functioning after surgery in middle-aged and elderly Danish twins.
Anesthesiology
2016
;
124
:
312
21
11.
Crosby
G
,
Culley
DJ
,
Hyman
BT
:
Preoperative cognitive assessment of the elderly surgical patient: A call for action.
Anesthesiology
2011
;
114
:
1265
8
12.
Culley
DJ
,
Flaherty
D
,
Reddy
S
,
Fahey
MC
,
Rudolph
JL
,
Huang
CC
,
Liu
X
,
Xie
Z
,
Bader
AM
,
Hyman
BT
,
Blacker
D
,
Crosby
G
:
Preoperative cognitive stratification of older elective surgical patients: A cross-sectional study.
Anesth Analg
2016
Mar 29. Epub ahead of print
13.
Phelan
EA
,
Borson
S
,
Grothaus
L
,
Balch
S
,
Larson
EB
:
Association of incident dementia with hospitalizations.
JAMA
2012
;
307
:
165
72
14.
Chan
MT
,
Cheng
BC
,
Lee
TM
,
Gin
T
;
CODA Trial Group
:
BIS-guided anesthesia decreases postoperative delirium and cognitive decline.
J Neurosurg Anesthesiol
2013
;
25
:
33
42
15.
Chen
PL
,
Yang
CW
,
Tseng
YK
,
Sun
WZ
,
Wang
JL
,
Wang
SJ
,
Oyang
YJ
,
Fuh
JL
:
Risk of dementia after anaesthesia and surgery.
Br J Psychiatry
2014
;
204
:
188
93