Swank Center for Memory Care and Geriatric Consultation, ChristianaCare
Cognitive impairment caused by an infection is not very common, but it is an important step in the evaluation of anyone suspected of having Alzheimer’s disease or other forms of dementia.
Many of my patients leave indelible traces in my memory, but a special place is reserved for those whose stories teach lessons that must never be forgotten. I had no idea, initially, how Marjorie’s story would join the other lessons that guide my clinical insights.* Her husband had called me, at the suggestion of a mutual friend, because of my expertise in late-life depression. Marjorie had become more withdrawn during recent weeks. She wasn’t exactly “sad,” her husband told me, and she was eating and sleeping as usual. She had stopped doing things she always loved, though, like her daily yoga practice. She seemed less engaged with her teenage children, which was very unlike her. Her memory had lost its usual sharpness recently. And, alarmingly, she was having more and more trouble working her computer and her cell phone. Her primary care doctor suspected depression and started an antidepressant, but the medication didn’t seem to be helping her.
As a geriatric psychiatrist, I recognized that Marjorie’s symptoms warranted careful evaluation. Even though she was only in her late 50s, very young for the onset of a dementia, her problem seemed unlike a routine case of depression. Her memory difficulty and her trouble carrying out tasks that had been simple a few months earlier suggested a neurocognitive problem such as delirium or dementia. The careful work of a local neurologist to whom I referred Marjorie led to a sad discovery. Marjorie was suffering from Creutzfeldt-Jakob disease, an infection of the brain that produces rapidly progressive dementia. Creutzfeldt-Jakob disease is a transmissible spongiform encephalopathy, sometimes called the human form of “mad cow disease,” and is caused by microscopic particles called prions, which are simple and potentially devastating proteins that cause certain host proteins to undergo a destructive change in shape. Although no curative treatment is available for this disorder, recognition of the diagnosis allowed Marjorie’s family to prepare for her death and to ease her final weeks of suffering by providing a palliative and loving environment.
Marjorie’s sad experience is a reminder that some cases of dementia are caused by infections of the brain or body, but not all these infections are as relentless as was hers. Recognition of an infection is critically important because some infections, detected early enough, can be halted or even reversed. Discovery of a treatable infectious cause of cognitive impairment is not very common, but it is an important step in the evaluation of anyone suspected of having Alzheimer’s disease or another dementias.
Infections that directly affect the brain are often missed by routine blood tests. Special testing is necessary to identify some of the most important brain infections that affect cognition.
HIV and AIDS
HIV infection, for example, can lead to the full range of neurocognitive symptoms from mild to severe. Cognitive impairment with HIV infection may be the first manifestation of AIDS, and this is often accompanied by problems with movement, speech, and behavior.
Syphilis
Syphilis is another transmissible infection that can produce severe cognitive changes in its later stages. It is possible to overlook or miss the significance of the earlier stages of infection.
Lyme Disease
Lyme disease, a common infection in northeastern and some southern regions of the United States, should be considered when evaluating a person whose cognitive ability has changed.
COVID-19 Infection
The full range of COVID-19 infection’s effects remain to be seen but early reports have identified the induction of acute delirium and have also suggested the possibility of longer-lasting neurocognitive effects. COVID-19 infection is associated with a storm of systemic inflammation as well as an increase in stroke risk, two mechanisms which might induce both acute and longer-term cognitive effects.
A Long List
These and many other central nervous infections can act directly on the brain through production of neurotoxins as well as more indirectly through initiating an inflammatory reaction that produces toxic byproducts. The list of potential brain infections is a long one that includes prions, fungi, bacteria, and larger parasitic organisms. Many infections are responsive to treatment.
In addition to the infections of the brain, another class of infections must be considered when evaluating a new cognitive change. These other diseases, located outside the central nervous system, are often treatable and sometimes cause great harm before they are discovered. Urinary tract infections (UTIs) or infections of the lungs are very common in older people who show confusion and the rapid change in alertness, attention, memory, and orientation called delirium. Delirium is often reversible once the cause is identified and treated. Simple blood tests and cultures of urine, blood, or sputum are used when clinicians search for these infections and for the antibiotics that will cure them.
Recent research has raised the possibility that Alzheimer’s disease pathology may bear a relationship to infection with a gum disease pathogen, Porphyromonas gingivalis. A current clinical trial is investigating the effect of a medication that inhibits the toxic brain effects of this organism.
What should a patient, or a patient’s family, do to make sure that infections are not overlooked in someone with suspected Alzheimer’s disease or another dementia? First and foremost, make sure to express your concern to the clinicians who are caring for someone with an altered mental state. Also, it is crucial to ensure that the patient’s history is known by his or her health care providers. This is especially important if the cognitive changes are recent, or developed rapidly, or were associated with a known medical illness or known exposure to an infectious disease. Identifying an infection can require special tests of blood or cerebrospinal fluid that are not routinely ordered in many treatment settings. Awareness of a disease history or of an exposure may lead to further assessment and earlier identification of an infection even when typical medical symptoms such as fever, cough, or pain with urination are subtle or absent.
Some infections, like Marjorie’s, cannot be cured. Her inevitable death was caused by a disease that is kept largely under control by public health measures that prevent us all from being exposed to infected beef. The cognitive effects of other brain infections, such as Lyme disease, can be halted and controlled even when not fully reversed. Delirium-inducing infectious diseases such as urinary tract infections, among the most treatable causes of cognitive impairment, can often be cured. No infection, however, should go unrecognized, so consideration of infections is an important step in the evaluation of any person with new changes in cognitive functioning.
*Marjorie’s details have been altered to disguise her identity.
James Ellison, MD received his medical degree from UCSF in 1978 and trained in psychiatry at the Massachusetts General Hospital (1979-1982).
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