To the Editor: The neuroanatomical basis for hyperphagia seen in patients with dementia is not well understood. We describe here a patient with marked hyperphagia associated with complete loss of satiety who provides clues to the site of involvement.
An 84-year-old man with progressive memory loss for 4 years was diagnosed to have Alzheimer’s disease and followed clinically over 3 years. His Mini-Mental State Examination (MMSE) score was 19. Language functions were normal. Cranial MRI scan revealed mild cortical atrophy. Serum B12, Folate, T3, T4, and thyroid stimulating hormone levels were normal. Marked hyperphagia (confirmed by detailed history1 and direct observation) was noted about 1 year after onset. Under direct observation, the patient was noted to complete a heavy meal (estimated 1800 calories) and a few minutes later to be eating again. He denied feeling full and said he wanted more food. Family members noted that he had larger meals and also ate more between meals. There was also evidence of searching for food—getting up in the middle of the night to eat an entire packet of biscuits or sugar—to an extent that food had to be hidden. However, on no occasion was he noted to have inappropriate behavior or hyperorality (examining or touching objects with lips). There was no history of wandering or eating inedible items. It was noted that concomitantly with marked hyperphagia there was progressive weight loss, from 130 pounds to 108 pounds over 3 years. Extensive physical examination and laboratory testing did not reveal any other abnormality.
Among the behavioral changes reported to occur in dementia are alterations in eating habits. Reduced food intake has been described in 16% to 63% of Alzheimer’s disease patients and increased food intake (hyperphagia) has been described in 9% to 26% of Alzheimer’s disease cases.2 In previous studies, excessive eating has been associated with weight gain, and greater frequency of wandering, unpredictable behavior, inappropriate dressing or bodily concerns and threatening self-harm, making it difficult to pinpoint the cause of the hyperphagia.3 As our patient was cooperative, and had no other behavioral abnormalities or language dysfunction, it was possible to make the important clinical observation that his hyperphagia was characterized by the complete absence of satiety. Meal size and termination is determined by the onset of satiety, a biological state induced by neurohumoral stimuli (such as gastric distension and the gut peptide cholecystokinin released into the circulation after a meal) that leads to meal termination.4 Recent research points to parasympathetic afferents activated by such stimuli converging on the nucleus tractus solitarius, an area of the caudal brain stem that plays an important role in satiety and meal termination.5 This hypothesis is supported by the finding that even in the absence of all hypothalamic influences, normal satiety is maintained.6
Involvement of brain stem nuclei (locus ceruleus, substantia nigra) has been described in Alzheimer’s disease.7 We speculate that damage to the nucleus tractus solitarius in the brain stem in our patient led to the loss of satiety and consequent hyperphagia. Additional damage to neurons in the cingulate gyrus or lateral hypothalamus may have led to excessive catabolic activity and weight loss in spite of markedly increased food intake. Neuropathological analysis in dementia patients with hyperphagia may further define the neuronal dysfunction underlying this curious behavioral abnormality.