Knee pain, mental decline and Alzheimer’s Disease

Ross A. Hauser, MD., Danielle R. Steilen-Matias, MMS, PA-C

Knee pain, mental decline, and Alzheimer’s Disease

Are you worried about Alzheimer’s and mental decline? If yes, then you should worry about your knee pain and you should re-examine your thinking on knee replacement or any procedure that requires general or regional anesthesia especially if you are over 60. This is not Caring Medical issuing these warnings, it is Caring Medical reporting on research on how NOT treating knee pain, or taking or not taking painkillers, OR getting a knee replacement can lead to cognitive decline and possibly Alzheimer’s disease. Please note: Knee replacements do help a lot of people. There are times when knee replacement is the only realistic option. This article intends to share information from recent research.

Are you at greater risk for Alzheimer’s disease if you have knee replacement surgery after the age of 60? Research says yes.

Are you at greater risk for Alzheimer's disease if you have knee replacement surgery after the age of 60?

We are going to start our understanding of knee pain and mental decline with a study published  (February 2018) in the Journal of Alzheimer’s Disease, (1) by University of Florida researchers.  In this paper, the researchers found 23 percent of adults age 60 and older who underwent a total knee replacement experienced a decline in activity in at least one region of the brain responsible for specific cognitive functions. Fifteen percent of patients declined across all brain networks the team evaluated. What does this mean? In a research summary issued by the Journal of Alzheimer’s Disease, the following points were made:

  • The University of Florida researchers conducted cognitive and brain imaging tests before and after surgery on 48 patients ages 60 and older undergoing a knee replacement.
    • Results were compared with age-matched (a control group) adults who have knee osteoarthritis but did not have surgery.
    • Participants who did not have surgery did not demonstrate any changes across the two brain scans, but 23 percent of participants who had knee replacement surgery showed large declines in connectivity in at least one brain network when tested 48 hours after surgery.
    • “It was surprising to observe such significant effects of orthopedic surgery on the human brain,” said Haiqing Huang, Ph.D., one of the study’s lead authors.

Patients who were cognitively weaker before surgery – with worse working memory, slowed mental processing, and evidence of brain atrophy as seen in imaging scans – demonstrated the biggest network declines after surgery.

A connection between cognitive decline and knee replacement surgery

This research was not the first to seemingly make a connection between cognitive decline and knee replacement surgery. In the December 2016 issue of the journal Medicine, (2) research led by a team from Seoul National University made these observations on Postoperative cognitive dysfunction.

  • Postoperative cognitive dysfunction occurs in 25.8% of elderly patients (over the age of 60 years) within 1 week after surgery and in 9.9% of patients between 1 week and 3 months after surgery.
  • Although various factors including the types of anesthesia and surgery, comorbidities (numerous and other health problems the patient has), and prior to the surgery conditions may contribute to Postoperative cognitive dysfunction, why they occur is still not known. But they do occur.

The researchers found their evidence concerning enough that they suggest that some patients should be given more extensive neurological testing before knee replacement surgery.

Severe post-operative cognitive dysfunction

A February 2022 paper in the journal BioMed research international (3) analyzed the risk factors and cognitive functional levels in elderly patients after total knee replacement. As pointed out in the research in this article, the study authors here write: “Cognitive dysfunction after total knee arthroplasty (replacement) is very common in elderly patients. Postoperative cognitive dysfunction (POCD), as a form of cognitive dysfunction, may affect patients’ short- and long-term recoveries.” The goal of this paper was to help doctors identify meaningful risk factors that may help reduce the occurrence of postoperative cognitive dysfunction (POCD) in the future.

Patients were assessed with a Montreal Cognitive Function Assessment Scale (MOCA – The highest best score is 30). The scores of 105 elderly patients were collected and according to the postoperative MOCA score, patients were divided into three groups:

  • Normal group
  • Mild Postoperative cognitive dysfunction (POCD) and
  • Severe Postoperative cognitive dysfunction (POCD) group

Summary findings:

  • Analysis revealed that a low preoperative MOCA score (more cognitive decline) and severe postoperative knee replacement pain were independent risk factors for mild and severe cognitive impairment, while a high postoperative CRP (inflammation) level was only an independent risk factor for mild cognitive impairment.

This study found that the level of preoperative cognitive function (in this case greater disability), postoperative CRP (more inflammation) level, and postoperative pain were independent risk factors for Postoperative cognitive dysfunction. Moreover, the levels of preoperative cognitive function and postoperative pain were more strongly correlated with severe Postoperative cognitive dysfunction than postoperative CRP levels.

Cognitive decline following a non-emergency elective knee or hip replacement

A 2021 paper in The Journal of Prevention of Alzheimer’s Disease (4) analyzed the determinants of cognitive decline following a non-emergency elective knee or hip replacement.

This was a study of  60 patients about the age of 72, with 72% being female.

  • Pre-operative benzodiazepine (anti-depressants) or anticholinergic treatments (urinary problems, Gastrointestinal disorders) were also associated with a drop in MOCA scores (more cognitive). Finally, the use of ketamine during anesthesia and the well-being evaluated before intervention were both linked to a reduced cognitive impact.

Older adults have a cognitive decline

A study published in the Journal of Alzheimer’s Disease (July 2018), (5)  shows that older adults can have a decline in three key resting-state networks (default mode network, central executive network, and salience network) after total knee arthroplasty and that patients’ pre-surgery brain and cognitive integrity predicts decline.

Now, what does this mean? First some definitions:

  • The default mode network is that part of your brain that allows you to shut off the outside world and let your mind wander or daydream.
  • The central executive network is that part of your brain that recognizes goals, solving problems within a set of guidelines (such as driving).
  • The salience network is believed to be responsible for understanding emotional and sensory stimulation.

Obviously, you can see how the decline in these three areas would be troubling to an older patient. What the researchers of this study found was a decline in these functions. They concluded: “Surgery with general anesthesia selectively alters functional connectivity in major cognitive resting-state networks, particularly in the default mode network and salience network. Participants with mild cognitive impairment appear more vulnerable to these functional changes.

The ability to draw a clock face after a knee replacement – researchers express concerns

In July 2019, a group of researchers led by a team from the University of Florida College of Medicine, Gainesville and including researchers from Massachusetts Institute of Technology, Rowan University, School of Osteopathic Medicine, Stratford, New Jersey ask 67 patients who underwent a knee replacement to draw a clock face at 3 weeks recovery and 3 months recovery. They also asked 66 patients who did not have knee replacement surgery to do the same thing. This is from the researcher’s published report from the medical journal Anesthesia and Analgesia. (6)

“This study revealed different clock drawing trajectories (speed and accuracy in the drawings) for older adults electing TKA (total knee replacement) relative to nonsurgical peers. On latency measures (total time and interdigit latency (again speed and accuracy)) of command and copy clock drawing conditions, total knee replacement participants were slower at 3 weeks following surgery. They required more time to complete their drawings and took long pauses between placing digits. Their performance after approximately 3 months of recovery approached their original drawing speed. By contrast, non-surgery peers demonstrated the opposite pattern, speeding up following baseline and then slowing slightly at 3 months.”

The conclusion: “Clock drawing construction slowed for nearly one-quarter of patients after total knee replacement surgery, whereas non-surgery peers showed the expected practice effect, ie, speed increased from baseline to follow-up time points.”

In other words, having a total knee replacement negatively impacted the cognitive skills of 25% of the patients.

Let’s point out that this research appeared in the journal Anesthesia and Analgesia. A journal that examines the impact of anesthesia during surgery. Below is another study from that journal.

Postoperative cognitive dysfunction (POCD), there is more

In 2014 in the journal, Anesthesia & Analgesia (7) doctors examining the “Fast-track,” accelerated knee and hip replacement recovery programs designed to reduce complications post-surgery found:

  • Postoperative cognitive dysfunction (POCD) is reported to occur after major surgery in as many as 20% of patients, elderly patients may especially experience problems in the weeks and months after surgery.
  • In this study, elderly patients who had a standard hip or knee replacement were “fast-tracked” to recovery by using Non-opioid multiple-drug pain management, (the management of post-surgical pain is seen as a priority component of making the “fast-track” recovery system work), early mobilization (getting ion your feet faster), and getting you out of the hospital as quickly as possible.


  • Initially good news. The incidence of POCD at 1 to 2 weeks was 9.1% and 8.0% at 3 months.
  • Longer-term, not such good news: “The incidence of POCD early after total hip and knee replacement seems to be lower after a fast-track approach than rates previously reported for these procedures, but late POCD occurred with an incidence similar to that in previous studies of major noncardiac elective surgery.”

We do see patients who were told of the “fast-track,” approach. It is in our opinion the right direction for people who MUST HAVE replacement surgery. In our opinion, not all knee and hip pain patients require replacement surgery.

Over 65? Living in an adult community? Getting by on painkillers for your knee pain? What are the painkillers doing to your brain?

University researchers in Israel visited people, over the age of 65, who lived in an adult community. What they wanted to explore was how many of these 65+ people lived with chronic pain and what chronic pain was doing to their health. Among the things that the researchers looked at was how chronic pain affected cognitive function.

These are the findings they published in the June 2018 issue of the Journal of Pain Research. (8)

  • More than half of the study participants reported pain that lasted for at least 3 months.
  • 94% of patients with chronic pain reported at least a moderate severity of pain and almost 60% complained of severe or very severe pain that had a negative effect on their daily activity.

The cognitive function connection: The use of painkillers – does it make cognitive function better or worse?

  • The study notes that past studies have raised an important question as to the association between painkillers administered for chronic pain and cognitive impairment:
    • in some cases, painkillers can cause cognitive impairment,
    • while in others, not only does analgesic therapy not cause cognitive impairment but it might even improve it.
    • However, only 41.4% of study participants with chronic pain took painkillers. The question is, were doctors afraid to offer painkiller prescriptions, or were people declining the medication to prevent sluggishness?

Chronic pain and painkillers may also accelerate Alzheimer’s Disease

More troubling news. Chronic pain can also accelerate Alzheimer’s Disease. A July 2019 study (9) in the prestigious journal Scientific Reports says this:

“In this sample of the Japanese general population, knee pain was prospectively associated with increased risk of dementia development particularly in individuals aged 65–79 years. The increased dementia risk in these individuals may be enhanced if they do not walk regularly.  . . Knee pain among older people, which is usually caused by osteoarthritis, is associated with inflammation. Persistent inflammation damages cerebral blood vessels and induces neuroinflammation (inflammation of nerves). Research shows that both vascular dementia and Alzheimer’s dementia are caused by inflammation. Individuals with knee pain are likely to have a high sedative load (a lot of painkillers), which can increase dementia risk. However, we suggest that knee pain (possibly accompanied by inflammation) itself, as well as physical inactivity, might increase dementia risk.”

What do you do then if memory and cognitive function is a concern?

What these and other studies show is that there is a connection between knee pain, knee pain treatments, cognitive decline, and Alzheimer’s disease. In our office, we utilize non-surgical, non-narcotic pain medication applications to assist our patients to solve their knee pain issues. Send us your questions about your knee pain.

Questions about our treatments?

While we do not treat Alzheimer’s or cognitive disease we do treat knee pain. If you have questions about knee pain and how we may be able to help you, please contact us and get help and information from our Caring Medical staff.

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1 Huang H, Tanner J, Parvataneni H, Rice M, Horgas A, Ding M, Price C. Impact of total knee arthroplasty with general anesthesia on brain networks: cognitive efficiency and ventricular volume predict functional connectivity decline in older adults. Journal of Alzheimer’s Disease. 2018 Jan 1;62(1):319-33. [Google Scholar]
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This article was update May 8, 2023

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