"I think cognitive problems are pretty rare" with statins, said Flourtown cardiologist David Becker, who took Walter off Lipitor. "But I don't think it's well-known among cardiologists or doctors in general."
That may be changing. Cognitive impairment associated with statins has been the subject of recent scientific papers, books, websites, and an untold number of reports - including Walter's - to MedWatch, the Food and Drug Administration's adverse-event reporting program.
"The topic is under active review within the agency," said FDA spokesman Morgan Liscinsky, who would not be more specific.
At the FDA's direction, makers of six statin brands have revised prescribing information in recent years to add "memory impairment" or "memory loss" to the list of adverse reactions reported since the products went on the market.
Pfizer Inc. - which in 2009 revised the package insert for Lipitor, the world's top-selling drug - stresses that the connection is speculative.
"The extensive clinical trial data regarding the safety and efficacy of Lipitor has not established a causal link between Lipitor and memory loss or other cognition-related side effects," company spokesman Raul Damas e-mailed. Lipitor's safety is "backed by more than 18 years of clinical experience and more than 200 million patient-years of experience."
He noted that the National Lipid Association's Statin Safety Task Force conducted an exhaustive review and concluded in 2006, "as for dementia and cognitive impairment, there is practically no evidence to support a link with statin therapy."
An estimated 25 million people worldwide are taking statins. Since the 1987 approval of the first brand, Mevacor, six more have come on the market, including Lipitor, which earned $11.8 billion in 2010.
In men who have had heart attacks or are at high risk of one, statins have been shown to reduce future attacks, strokes, and death. But the benefits of inhibiting cholesterol production in lower-risk groups such as healthy women and the elderly are not as clear, and some doctors say the pills are being overprescribed.
Muscle aches and weakness are the most commonly reported side effects of statins. Its fatal form, rhabdomyolysis, led to the removal of Baycol from the market in 2001.
No one can say how rare cognitive problems are.
"The range of severity of cognitive problems can be great," said Beatrice Golomb, a University of California, San Diego doctor. "And physicians generally dismiss the possibility of a relationship."
Golomb has become a leading statin-effects researcher, as well as a lightning rod for skeptics who criticize her methods.
Through the Internet and media stories, patients have learned of her website, statineffects.com, and answered a questionnaire about their experiences. For one study, Golomb surveyed 422 patients who had self-reported cognitive problems, then used a drug-reaction probability tool to conclude that 128 were probably or definitely related to statins.
Diagnosing a patient with statin-induced dementia can be tricky.
"Many patients at risk for this complication also fit the profile of other types of dementia," University of Mississippi Medical Center researchers wrote in the journal Pharmacotherapy in 2004.
Their article described two women in their late 60s who exhibited disturbing changes in mood, memory, motivation, and behavior that coincided with statin use. One woman, who had been on Lipitor for a year, developed symptoms soon after her dosage was increased. The other woman went on and off Lipitor twice and then tried Zocor in the futile hope that mental impairment would not return.
Both women's problems resolved when therapy was stopped.
But what if the problems persist or improve only a little after therapy is stopped? Does that mean the statin triggered, or worsened - or played no role at all in - a neurological disease process?
"There's no test to find out," Becker said.
John deVecchis, 74, illustrates this complexity.
His wife, Rita, says that in 2004, when his Lipitor dose was doubled, he was a robust, tournament-level racquetball player and a peripatetic photographer of jazz musicians who proudly displayed his pictures in their South Street gallery.
Over the next four years, his physical, mental, and personality changes grew so severe that most people who saw him "thought he was a stroke victim," she said.
That year, she took him off Lipitor, convinced after searching the Internet that it had damaged his brain and his muscles.
But other factors may have been involved. The year his Lipitor dose went up, he fell and needed hip-replacement surgery, which caused blood-clotting complications. And early this year, he was diagnosed with a rare brain disorder that causes serious problems with walking and balance; in some patients, it also causes progressive mild dementia.
"He's been off it [Lipitor] a long period of time, and things haven't turned around that much," said his University of Pennsylvania neurologist, Steven E. Arnold.
In Rita's view, her husband has improved significantly, particularly his communication and social skills. But she realizes some damage may be permanent.
"I want my husband back," she said. "I just don't know if it will happen."
In the 1990s, many researchers - and drug firms - hoped that statins might actually ward off dementia.
Population studies suggested that Alzheimer's and other forms of dementia were less common in people who took statins than those who didn't. Researchers theorized that the drugs, which block an enzyme needed to produce cholesterol, also reduced the brain inflammation and plaques that are characteristic of Alzheimer's.
However, two large clinical trials - the most rigorous type of study - subsequently showed that statins were no better than placebo at preventing dementia in high-risk people.
"It just didn't work," Arnold said.
A very different mechanism is believed to be linked to thinking problems.
Cholesterol is vital to brain function, and is abundant in the sheaths that insulate nerve cells. And the enzyme that statins interrupt is involved in the synthesis of coenzyme Q10, a vitamin-like substance that the cell's mitochondria need to convert food and oxygen into energy.
"Converging evidence," Golomb wrote in 2008, supports the theory that mitochondrial disruption underlies muscle problems linked to statins, and possibly also cognitive impairment.
Paul D. Thompson, director of cardiology at Hartford Hospital in Connecticut, has identified three gene variations that may predispose people to statin intolerance.
In a small, preliminary study using sophisticated brain imaging, he also found brain function of people taking a high dose of Lipitor was "distinctly different" from those on a placebo - even though none of them knew if they were taking the drug or perceived any side effects.
With the statin, "the brain seemed to be more active when trying to learn a task and when trying to remember the task," Thompson said.
For Walter, eschewing statins was not easy. He inherited a gene that makes him prone to extremely high cholesterol and has a family history of heart disease.
Under Becker's guidance, he has changed to a healthy but restrictive Mediterranean diet. He also takes cholesterol-fighting dietary supplements including red yeast rice and fish oil.
And he is back to multitasking.
"Now, my desk is sloppy, but it's not like I need Post-it notes," he said.
Contact staff writer Marie McCullough at 215-854-2720 or firstname.lastname@example.org.