Reversible Dementia as a Result of Herbal Supplements and Medications

Authors: 

Melinda S. Lantz, MD

Citation: 

Pages 15 - 18

Case Presentation

Mrs. S is a 72-year-old widowed woman who is brought to the Emergency Department (ED) by her daughter. Mrs. S’s daughter, Mrs. B, returned from a 6-month stay in Europe and found her mother to be weak, pale, and confused. Mrs. B tells the ED staff that her mother has always taken a number of herbal and nutritional supplements in addition to medications for “indigestion.” Mrs. S has been followed in the past by a primary care physician but has not had any regular medical care since her doctor retired two years earlier. Her daughter brought a number of bottles of prescription medications and supplements that she found in her mother’s kitchen cabinet. These include esomeprazole 40 mg, famotidine 20 mg, and a variety of herbal preparations including alfalfa seeds, powdered ginger root, Siberian and Korean ginseng root, ginkgo biloba tablets, echinacea tablets, and several bags of ground leaves without any labels. Mrs. B reports that her mother was treated for peptic ulcer disease many years ago and believes that she has been taking the esomeprazole and famotidine chronically.

Mrs. S is found to appear weak and pale. She is oriented to her name and recognizes her daughter but is unable to provide her address or telephone number. She frequently repeats the questions that are asked to her in an echolalic manner. She asks for a cup of tea and points toward the bag of herbal supplements that her daughter brought. Mrs. S indicates that she takes several doses of these each day and makes tea to “soothe her stomach.” She remains calm but confused and allows her blood to be drawn and an intravenous line inserted for hydration. She is mildly tachycardic with a heart rate of 110 beats per minute. Her electrocardiogram shows sinus tachycardia. Her lab results are troublesome. Mrs. S is anemic with a hemoglobin of 8.3 g/dL (12-15 g/dL) and a hematocit of 24% (36-44%). Her mean corpuscular volume (MCV) is elevated at 108 fL (80-100 fL). Her electrolytes were within normal limits, but her albumin 2.5 g/dL (3.2-5 g/dL) and total protein 5.2 g/dL (6.5-7.9 g/dL) were low.

Mrs. S is admitted to the hospital for further evaluation of her anemia and confusion. There was concern that she was suffering from a malignancy, malnutrition, gastrointestinal blood loss, and, potentially, dementia. Mrs. S is found to be both iron- and vitamin B12–deficient. Her serum iron level is 25 µg/dL (65-150 µg/dL), and vitamin B12 level is 140 pg/mL (200-900 pg/mL). She undergoes endoscopy and colonoscopy, which are negative for malignancy. A neurology consult reveals confusion with recent memory loss with a mild gait disturbance. A computed tomography scan of the head reveals mild atrophy. Tests of her thyroid, liver, and kidney function were normal. Urine toxicology was negative. A diagnosis of dementia is considered.

Mrs. S is started on vitamin B12 supplementation with daily injections and is given oral iron therapy. Her daughter visits daily and encourages her mother to eat. After several days, Mrs. S appears less confused and more responsive. She tells the staff that she has been visiting a local “nutrition consultant” who runs an herbal and dietary supplement store. She has been drinking herbal teas and taking the supplements her daughter found in her house. Mrs. S continued to take both esomeprazole and famotidine daily, as she found that many of the herbal supplements upset her stomach. She often skipped meals because she did not feel hungry after drinking the herbal teas.

After 5 days in the hospital, Mrs. S is discharged home with her daughter. She is advised to follow up with an internist for continued vitamin B12 injections and to avoid all herbal preparations. Mrs. S is referred to both a psychiatrist and neurologist for outpatient follow-up of her memory loss, unsteady gait, and due to concerns that her decline in eating with use of many unusual herbal products is related to dementia or depression.

Discussion 

The majority of cases of dementia can be and are diagnosed based on outpatient medical and psychiatric evaluations.1 While moderate-to-severe dementia is easier to recognize, milder dementia is often not detected. Patients may not recognize or acknowledge symptoms in themselves, and therefore do not report complaints, making an independent informant who knows the patient critical in the evaluation process.2 The mental status evaluation is one of the most important parts of the dementia evaluation and needs to be administered in a calm environment. More than 50% of people with dementia are not diagnosed by a physician until they begin to display disruptive behavior or gross impairment in self-care.1,2 

Two key clinical features underlie the concept of dementia: (1) the affected person has experienced a decline from some previously higher level of functioning, and (2) the cognitive loss significantly interferes with work or usual social activities. The cognitive loss of dementia must include both memory impairment and a decline in at least one other area, such as aphasia (loss of language or speech), agnosia (loss of recognition), apraxia (loss of ability to perform motor tasks), or executive dysfunction (loss of ability to plan, initiate, or monitor behavior or activities).1,2

A reliable history is a major element in determining the correct diagnosis in an older adult who presents with memory loss or confusion.1 An informant who is familiar with the patient’s daily functioning and behavior is vital to establish the nature of the impairment. The history must focus on the nature of the memory loss, the timeframe in which it has occurred, and any acute changes that may have accompanied the decline.1,2 This case illustrates a patient who presents with a relatively acute onset in symptoms accompanied by generalized weakness. This is significant, as a diagnosis of dementia cannot be considered in the context of an acute change in mental status and functioning. Other causes of the patient’s symptoms must be considered, notably delirium and reversible cognitive loss3 (Table1-3).

The core features of delirium include the acute onset of an altered level of consciousness, impaired attention (which may include diminished ability to focus, sustain, or shift attention) and impairments in other realms of cognitive function. These may include disorientation and decreased memory, and unpredictable fluctuations in severity of the impairments with sleep-wake cycle disturbances. Abnormalities of perception, thinking, or mood often are present but are not necessary for a diagnosis of delirium. Disturbance of consciousness with reduced ability to focus, sustain, or shift attention is the hallmark of delirium.3

Assessment of medications, including over-the-counter drugs and nutritional supplements, is an important aspect in the evaluation of cognitive loss.1-3 Older adults are high utilizers of vitamins and herbal and nutritional supplements. Up to two-thirds of community-dwelling elderly persons report using at least one type of vitamin or supplement, with 20% reporting regular use of herbal products.4 Of concern is that less than 10% of older adults who utilize herbal and nutritional supplements discuss these products with their physicians.5 Vitamins, herbal products, and dietary supplements are poorly regulated, and the purity of the ingredients is often questionable.4-6

Many commonly used herbal preparations have been associated with significant side effects and drug-drug interactions.6 Several herbal products have been found to contain the banned substance ephedra, which is associated with cardiac events, hypertension, and central nervous system stimulation.5,6 Garlic, ginkgo, and ginseng have been associated with prolonged bleeding and potentially dangerous interactions with anticoagulants such as warfarin.5-7 Ginseng may cause or potentiate hypoglycemia. It is also associated with headaches and changes in blood pressure.6 The herbal preparations kava and valerian may interact with sedatives and general anesthesia if the patient requires emergent surgery. Kava has been associated with cases of hepatitis, including fatalities. The commonly used herbal derivative St. John’s wort has the potential to interact with antidepressants, antihypertensives, and sedative-hypnotic agents.5-7

The gastrointestinal upset noted by the case patient is a common side effect of many herbal preparations.5-7 In this case, it led to the continued use of both a histamine-2 blocking agent and a proton pump inhibitor, which also contributed to the vitamin B12 deficiency found in the patient.8,9 Of ongoing concern is the likelihood of an increase in both herb-herb and herb-drug interactions among patients who utilize these products. It is vital that the physician actively inquire about the use of herbal supplements at each visit and encourage the patient to bring in the products for discussion.

Information regarding herbal and nutritional products is available from the National Center for Complementary and Alternative Medicine website at http://nccam.nih.gov/health.

Outcome of the Case Patient  

Mrs. S was evaluated by a psychiatrist 6 weeks following her discharge from the hospital. She was seeing her new primary care physician regularly and also saw the neurologist, who remained concerned about the possibility of a slight unsteady gait related to the vitamin B12 deficiency. She was no longer using any herbal preparations and continued to take ferrous sulfate and receive vitamin B12 injections. She was living with her daughter, but was planning to return to her own home. Mrs. S was able to provide a coherent history, which was supported by her daughter. She indicated that she was always interested in “natural foods” and had started buying alfalfa seeds, ginseng, and ginger from a new store that opened near her house. The owner of the store would frequently recommend additional products to her, and she was visiting him weekly. When Mrs. S started feeling weak and tired, she discussed her symptoms with the store owner, who recommended additional teas and products. Mrs. S reported that she had visited a local primary care physician about her stomach pain, but was reluctant to discuss her use of herbs and teas. She reported feeling embarrassed that she was buying so many products and admitted that she could not keep track of exactly what was in each bag. By the time her daughter had returned from Europe, Mrs. S admitted that she had become very weak and was spending most of her days in bed.

After her discharge from the hospital, Mrs. S agreed to stop all of the herbal preparations. Mrs. S was no longer feeling weak and was performing all of her own personal care. She was able to cook and helped her daughter with household tasks. On mental status examination Mrs. S was alert, very verbal, and displayed a pleasant mood. Her affect was reactive and she had no signs of any thought disorder or psychotic symptoms. Her cognition appeared intact. She was oriented to person, place, and date. She was able to perform calculations, recall objects, and accurately draw a clock with the correct time. She was able to describe how to pay her bills and calculate getting the correct change when buying food from a store.

Mrs. S appeared to have suffered an episode of delirium as a result of the use of multiple herbal preparations and prescription medications that resulted in anemia, generalized weakness, and nutritional deficiency. At the time of her psychiatric evaluation, no cognitive loss was present. Her anemia was being treated and she had stopped taking all of the potentially offending medications and supplements. Mrs. S agreed to return to the psychiatrist and neurologist for a follow-up evaluation of her mood and cognitive status on a periodic basis.

The author reports no relevant financial relationships.

References
1. APA Work Group on Alzheimer’s Disease and Other Dementias, Rabins, PV, Blacker D, Rovner BW, et al. American Psychiatric Association practice guideline for the treatment of Alzheimer’s disease and other dementias. Second edition. Am J Psychiatry 2007;164(12 Suppl):5-56.

2. Feldman HH, Jacova C, Robillard A, et al. Diagnosis and treatment of dementia: 2. Diagnosis. CMAJ 2008;178(7):825-836.

3. Moraga AV, Rodriguez-Pascual C. Acurate diagnosis of delirium in elderly patients. Curr Opin Psychiatry 2007;20(3):262-267.

4. Cheung CK, Wyman JF, Halcon LL. Use of complementary and alternative therapies in community-dwelling older adults. J Altern Complement Med 2007;13(9):997-1006.

5. Gardiner P, Phillips R, Shaughnessy AF. Herbal and dietary supplement-drug interactions in patients with chronic illnesses. Am Fam Physician 2008;77(1):73-78.

6. Ernst E. The risk-benefit profile of commonly used herbal therapies: Ginkgo, St. John’s Wort, Ginseng, Echinacea, Saw Palmetto, and Kava [published correction appears in Ann Intern Med 2003;138(1):79]. Ann Intern Med 2002;136(1):42-53.

7. Bent S. Herbal medicine in the United States: Review of efficacy, safety, and regulation: Grand rounds at University of California, San Francisco Medical Center. J Gen Intern Med 2008;23(6):854-859. Published Online: April 16, 2008.

J Am Med Dir Assoc 2008;9(3):162-167.

9. Hirschowitz BI, Worthington J, Mohnen J. Vitamin B12 deficiency in hypersecretors during long-term acid suppression with proton pump inhibitors. Aliment Pharmacol Ther 2008;27(11):1110-1121. Published Online: February 27, 2008.

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