Weight Loss in Advanced Alzheimer's Disease, Part I: Contributing Factors and Evaluation

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Weight loss is a common occurrence in advanced Alzheimer's disease. Part I of this two-part article discusses the factors associated with the pathophysiology and progression of Alzheimer's disease that may promote weight loss, and the appropriate evaluation of weight loss and malnutrition. Factors such as abnormal eating behaviors, behavioral disturbances, oropharyngeal dysphagia, taste and smell dysfunction, and the effects of proinflammatory cytokines influence the balance between energy intake and energy expenditure, making stability more difficult to maintain and promoting a tendency toward weight loss. Many other conditions along with medication effects may also contribute to weight loss and nutritional decline. Appropriate nutritional care for the patient with Alzheimer’s disease with weight loss starts with a thorough assessment to identify all the contributing factors. The evaluation should include a review of medications, medical history, and a thorough physical examination.

This article is the first part of a two-part series.


Heidi K. White, MD, MHS. Weight Loss in Advanced Alzheimer’s Disease, Part I: Contributing Factors and Evaluation. Annals of Long-Term Care: Clinical Care and Aging: 2004;12[5]:33-37.

From the Center for the Study of Aging and Human Development and Division of Geriatrics, Department of Medicine, Duke University School of Medicine, and Geriatric Research Education and Clinical Center, Durham VAMC, Durham, NC.


INTRODUCTION

Nursing facilities that care for patients with advanced dementia are committed to providing high-quality nutritional care for all residents. These standards set forth in federal regulations state, “Based on a resident’s comprehensive assessment, the facility must ensure that a resident maintains acceptable parameters of nutritional status, such as body weight and protein levels, unless the resident’sclinical condition demonstrates that this is not possible.” [1] Alzheimer’s disease (AD) frequently involves weight loss, [2-7] which is a strong predictor of mortality. [8] Whether nutritional intervention can delay functional decline and morbidity is largely untested. However, observational data from subjects with AD indicate that weight gain is associated with a reduced risk of mortality. [8] Similar data in institutionalized subjects, including those with dementia, show that weight gain of even small amounts can improve morbidity and mortality. [9] Weight loss and subsequent malnutrition may be an unavoidable part of the natural history of end-stage AD and other dementias. However, a careful understanding of the nutritional consequence of Alzheimer’s disease, along with an appropriate assessment and a thoughtful approach to intervention, may help to avoid the complications associated with malnutrition, thus preserving a better quality of life up until death.


FACTORS IN WEIGHT LOSS

Abnormal Eating Behavior

Abnormal eating behaviors contribute to weight loss. Typical behaviors include needing frequent verbal cues to complete the eating process, verbally refusing food, pocketing food in the cheeks without swallowing, clenching teeth, and spitting food. [10,11] Abnormal eating behavior may be subtler, such as fluctuations in appetite, delusions about food (eg, believing food is poisoned), increased distractibility at mealtime, and changes in food preferences. [12] Destruction of the hippocampus and surrounding cortical areas may explain certain behaviors. In late-stage AD, plaques and tangles have been described in the hypothalamus, the neurologic center of appetite regulation. [13,14]

Dysphagia is a common manifestation of late-stage AD. [15,16] Even in early-stage AD, an increased duration of the oral and pharyngeal components of swallowing have been observed. [17]


Taste and Smell Dysfunction

Taste and smell dysfunction occurs with normal aging and can be exacerbated by medications and disease. [18,19] Although some changes in taste perception have been reported, [20] gustatory dysfunction has not been studied as thoroughly as olfactory dysfunction in Alzheimer’s disease. Multiple studies in subjects with mild to moderate Alzheimer’s disease have demonstrated deficits in odor identification. [21,22] In addition, odor threshold may become progressively more abnormal as the disease progresses. [23] Furthermore, patients with AD are often unaware of their decreased smell sensitivity. [24] Olfactory pathways are among the first areas of the brain to exhibit the typical pathology of amyloid plaques and neurofibrillary tangles. [25] Olfactory dysfunction may not be specific to Alzheimer’s disease; similar olfactory deficits have been noted in Parkinson’s disease and vascular dementia. [26]


Inflammatory Mediators

Cytokines such as interleukin-6 (IL-6) are an integral part of anorexia-cachexia syndromes in other disease states such as cancer and heart failure. [27,28] Cytokines, including IL-1, IL-6, and tumor necrosis factor (TNF)-alpha, play an important role in the inflammatory process that accompanies the hallmark changes of amyloid plaques and neurofibrillary tangles that occur with AD. [29-32] Cytokines produced by the local inflammatory reaction in the brain may be sufficient to produce changes in neurotransmitters, neuropeptides, and hypothalamic neurons to cause anorexia.


Balancing Energy Intake and Expenditure

Although inadequate oral intake is likely the primary cause of weight loss in moderate-to-severe AD, increased energy expenditure could contribute to a mismatch between energy intake and energy expenditure that leads to weight loss. It has been suggested that resting metabolic rate may be elevated in AD. However, several studies now confirm that there is no evidence that resting metabolic rate is elevated in subjects with Alzheimer’s disease compared to older adults without dementia. [33,34] The idea that physical activity in the form of behavioral disturbances (eg, pacing) may contribute to increased energy expenditure has not been supported either. [35] Unfortunately, there are no data on patients with AD during the dynamic phase of weight loss. It is evident from our work and that of others that not all patients with AD are losing weight all of the time. [8,36] There can be periods of acute weight loss, a slow gradual weight loss, and variations in weight, which may include periods of substantial weight gain.

It is possible that relatively subtle and perhaps intermittent changes in factors such as behavioral disturbance, which influence both energy intake and energy expenditure, may tip the balance toward weight loss for patients with AD. This imbalance may be multifactorial and intermittent. Rather than one particular cause or abnormality leading to weight loss, AD may lead to a condition in which changes in energy intake and expenditure are not easily compensated. Preliminary data from institutionalized subjects with AD show that body mass index (BMI) is inversely correlated with a measure of behavioral symptoms, which indicates that lower BMI was associated with higher frequency and severity of behavioral problems. [37] Certain individual behavior scores showed significant inverse correlation with weight change, indicating that as these behaviors increased over the time period weight tended to decrease.

In summary, both primary and secondary factors may contribute to weight loss in advanced AD. [38] Primary factors such as those discussed thus far are attributable to the pathophysiology of Alzheimer’s disease and may or may not be amenable to intervention. Secondary factors are not attributable to the pathophysiology of AD but are commonly encountered conditions that may contribute to weight loss, and are perhaps more amenable to intervention (Figure).


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Figure: Primary and secondary factors that may contribute to weight loss in advanced Alzheimer’s disease.

Primary Factors
• Taste and smell dysfunction
• Proinflammatory cytokines
• Behavioral disturbances
• Abnormal eating behavior
• Oropharyngeal dysphagia


Secondary Factors
• Feeding dependence
• Acute/chronic illness
• Medication
• Restrictive diet orders
• Oral/dental problems
• Depression
• Constipation
________


EVALUATING WEIGHT LOSS AND MALNUTRITION

When to Evaluate

Periodic weight measurements are a primary resource for monitoring nutritional status and recognizing change. Most residents of nursing facilities are weighed monthly unless their condition would warrant weekly monitoring. Maintaining functional equipment, staff instruction in equipment use, and accurate systematic documentation are important. According to parameters set for the Minimum Data Set, weight loss of 5% in 1 month or 10% in 3 months is considered of clinical importance and should entail further evaluation (Table I). BMI (weight in kilograms divided by height in meters squared) is a helpful measurement of nutritional status. Older adults with a BMI of < 21 are likely to be malnourished. [39] Conditions such as pressure ulcers that increase nutritional requirements should also prompt evaluation. Although laboratory parameters such as cholesterol and albumin levels may be helpful as a means of diagnosing malnutrition and gauging the effectiveness of interventions, effective nutritional surveillance should recognize threats to nutritional status long before abnormal biochemical indices are sought. [40] Whether identified by body weight parameters or chemical indices, protein–calorie malnutrition is prevalent in long-term care. [41] Most important, all indicators should be recognized and assessed not only by the consulting dietician, but also by the nurses and physician so that a comprehensive nutrition intervention plan, which reflects the goals of care for the individual patient, can be developed and implemented.


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Table I: Triggers for Evaluation

Weight loss of 5% in 30 days or 10% in 3 months
Body mass index ≤ 21
Pressure ulcer, infection, or other condition that increases nutritional needs

Other indicators of poor nutrition:
- Albumin < 3.4 g/dL
- Cholesterol < 160 mg/dL
- Hemoglobin < 12 g/dL
- Transferrin < 180
________


Other Illnesses

Common infections such as pneumonia or urinary tract infection will often produce anorexia. Cancer, thyroid dysfunction, and other common causes of weight loss are part of the differential diagnosis. Constipation is a common condition in institutionalized individuals because of decreased fluid intake, decreased physical activity, and medications that promote this condition. Chronic constipation can have a profound impact on appetite yet can be difficult to identify in patients with cognitive impairment. Chronic pain may also be difficult to identify but can significantly impair appetite.


Medications

Medications should be reviewed. Commonly used drugs can cause many symptoms that potentially limit caloric intake (Table II). [42] Acetylcholinesterase inhibitors, which are the primary treatment for the cognitive symptoms of AD, have several potential adverse effects including nausea, vomiting, and anorexia that may contribute to weight loss. [43,44] Additionally, galantamine has been associated with an increased incidence of weight loss. [45] Patients with dementia may not be able to voice symptoms attributable to these drugs.


________
Table II: Medications That Limit Caloric Intake

Medication Type -- Medication-Induced Symptoms
- Sedatives, opioids -- Inattention
- Antipsychotics -- Movement disorders
- Anticholinergics -- Xerostomia
- Bisphosphonates (eg, alendronate) -- Esophagitis
- Antibiotics -- Anorexia, nausea, metallic taste
- Nonsteroidal anti-inflammatory drugs -- Anorexia
- Toxic levels of drugs (eg, digoxin, theophylline) -- Nausea
- Phenothiazines, haloperidol -- Dysphagia [42]
________


Depression

Depression is a common treatable cause of weight loss in older adults. Each patient should be specifically evaluated for depression and aggressively treated when it is suspected to be present. Depression is a common occurrence in early dementia but may also be present in more advanced disease.


Don’t Forget the Mouth

Dental abnormalities such as ill-fitting dentures, tooth decay, and abscess formation may contribute to weight loss. Dry mouth and antibiotic use can lead to thrush, a yeast infection that can cause discomfort and unwillingness to eat.


Dysphagia

Patients with advanced dementia often develop serious difficulties swallowing. They may resist food being placed in the mouth, fail to manage the food bolus once it is in the mouth (oral-phase dysphagia), or aspirate when swallowing (pharyngeal-phase dysphagia). Family members and caregivers should be encouraged to report changes in eating behavior and signs of dysphagia. Coughing and choking during eating are common signs of aspiration. See Table III for additional signs of dysphagia. So-called “silent aspiration” occurs when patients with advanced dementia suffer the consequences of aspiration without any identifiable signs. A swallowing evaluation by a speech therapist that includes visualization of the swallow, either in a barium study or by fiberoptic techniques, can be helpful in determining the presence and severity of swallowing dysfunction. Although this evaluation can be helpful, many patients experience the sequelae of aspiration but do not demonstrate aspiration on such testing. Additionally, many patients who clearly aspirate on testing do not seem to suffer obvious consequences of aspiration such as weight loss or aspiration pneumonia. Some researchers have attempted to identify risk factors that might predispose patients with dysphagia to aspiration pneumonia (Table IV). [46]


________
Table III: Clinical Signs Suggestive of Dysphagia

- Cough or choke before, during, or after swallow
- Difficulty managing secretions
- Wet, gurgly voice after swallow
- Food or liquid leaking from the nose
- Pocketing food in the oral cavity
- Increased time to complete meal
- Prolonged chewing or oral preparation
________


________
Table IV: Risk Factors for Aspiration Pneumonia

- Dysphagia

- Feeding dependence

- Oral care dependence

- Number of decayed teeth

- Tube feeding

- Multiple medical diagnoses

- Number of medications
________


SUMMARY RECOMMENDATIONS

A physician should evaluate the patient with advanced AD who is losing weight, has a low BMI, or has unmet nutritional needs (eg, pressure ulcers). A thorough medical history and physical examination should be done. The physician, nutritionist, speech therapist, nurse, direct care worker, and family should contribute to the process of evaluation and the implementation of the nutrition care plan. All of these individuals must work together to ensure that weight loss and malnutrition are recognized, evaluated, and treated. The effectiveness of each intervention must be evaluated. Maintaining nutritional health will not always be possible. The goals of care must be clear to all involved, which may range from expected improvement in nutritional status to supportive and palliative care in the face of an advanced and terminal condition. The goals of care are likely to evolve as assessments are made and interventions evaluated. The nursing home medical director and primary care physicians of individual patients must provide leadership to this process, especially when alternatives to oral feeding are considered. The leadership within individual nursing facilities should discuss and determine their evaluation and implementation process for recognizing and intervening to prevent weight loss and nutritional decline. Nutritional policies and procedures need to include not only the recognition and treatment of weight loss, but also a plan for palliative and supportive care that includes careful hand feeding when end-stage dementia precludes our ability to overcome nutritional decline.

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Part II will discuss interventions for weight loss in Alzheimer’s disease.

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