Energy expenditure, energy intake, and weight loss in Alzheimer disease

¹ From the Division of Clinical Pharmacology and Metabolic Research, the Department of Medicine, University of Vermont, Burlington.

² Portions of this review were published previously (J Nutr Health Aging 1998;2:115–8).

³ Supported by grant AG-07857 from the National Institute of Aging, Research Career and Development Award KO4-AG00564 (to ETP), the American Association of Retired Persons Andrus Foundation and Alzheimer's Association/Red Apple Companies Pilot Research grants (to ETP), and grant RR-109 from the General Clinical Research Center at the University of Vermont.

⁴ Address reprint requests to ET Poehlman, Division of Clinical Pharmacology and Metabolic Research, Department of Medicine, Given Building C-247, University of Vermont, Burlington, VT 05405. E-mail: epoehlma{at}zoo.uvm.edu.

ABSTRACT  
Alzheimer disease is one of the leading causes of death among older individuals. Unexplained weight loss and cachexia are frequent clinical findings in patients with Alzheimer disease. Thus, it has been postulated that Alzheimer disease may be associated with dysfunction in body weight regulation. This brief review examines the interrelations among energy intake, energy expenditure, and body composition in Alzheimer disease. We explored whether abnormally high daily energy expenditures, low energy intakes, or both contribute to unexplained weight loss and a decline in nutritional status. Specifically, we considered studies that examined energy intake, body composition, and daily energy expenditure and its components. The application of doubly labeled water and indirect calorimetry to understand the etiology of wasting has increased our knowledge regarding the relation among energy expenditure, physical activity levels, and body composition in Alzheimer disease patients. Although the number of studies are limited, results do not support the notion that a hypermetabolic state contributes to unexplained weight loss in Alzheimer disease, even in cachectic patients. Recent findings are presented suggesting an association between abnormally elevated levels of physical activity energy expenditure and elevated appendicular skeletal muscle mass and energy intake in Alzheimer disease patients. Clinical strategies aimed at developing lifestyle and dietary interventions to maintain adequate energy intake, restore energy balance, and maintain skeletal muscle mass should be a future area of investigation in Alzheimer disease research.

Key Words: Alzheimer disease • energy expenditure • weight loss • body composition • metabolic rate • cachexia • dementia • elderly • aging

INTRODUCTION  
As the population of the United States ages, an important demographic and epidemiologic trend has emerged: an increase in the number of persons with Alzheimer disease and related disorders (1). The prevalence of Alzheimer disease was estimated at 3.75 million cases in 1990, representing >10% of the total population aged 65 y. Other investigators have suggested that the prevalence of Alzheimer disease may actually be higher than these estimates (2–4). Nine million cases of Alzheimer disease are projected by the year 2040. The estimated prevalence of severe dementia for persons aged 85 y (the "oldest old") is much higher, ranging from 25% to 45% (5). Dementia of the Alzheimer type is an incurable and progressive neurologic degenerative disorder that leads to a gradual loss of independence and is one of the leading causes of death among elderly people (6). The onset of the disease usually occurs at 80 y of age, but the early-onset form can occur as early as the mid-20s. A characteristic course usually begins with amnesia and anosmia and proceeds to effects on language and motor skills, with incontinence and gait disorder occurring in later stages (7). The deleterious nature of this incurable disease is a significant burden on our health care system as well as on the lives of the patients' families and caregivers. Although it may not yet be possible to prevent, treat, or permanently alter the course of the underlying disease, identification and amelioration of body habitus problems may prove to be one strategy for lessening the burden of the disease.

Substantial weight loss is a frequent clinical finding in patients with Alzheimer disease. The National Institute of Neurological and Communicative Disorders and Strokes Task Force on Alzheimer's Disease has included weight loss as a "clinical feature consistent with the diagnosis of Alzheimer's disease" (8). Loss of body weight is typically associated with reduced muscle mass, which leads to loss of functional independence and eventually increased supervision from caregivers. The loss of body weight also increases the risks of decubitus ulcers, systemic infection, and mortality, leading to a greater consumption of health care resources (9, 10). Several studies report energy malnutrition in Alzheimer and demented patients on the basis of biochemical or anthropometric measurements (11, 12). It has even been suggested that malnutrition may be a factor in the etiology of dementia and other psychiatric and cognitive disorders (13), although all studies do not support this finding (12). In short, although loss of body weight with its attendant clinical hazards often complicates Alzheimer disease, the causes of this weight loss remain unknown. Thus, an understanding of the pathogenesis of weight loss has important therapeutic implications for the management of Alzheimer disease patients.

IS WEIGHT LOSS IN ALZHEIMER DISEASE CAUSED BY INADEQUATE ENERGY INTAKE?  
It is presently unclear whether the energy imbalance and the accompanying weight loss associated with Alzheimer disease are caused by reduced energy intake, elevated energy expenditure, or a combination of the 2. A common clinical observation is that most demented patients, especially those with Alzheimer disease, lose weight during the progression of the disease, particularly in the final stages. For example, White et al (14) showed that nearly twice as many subjects with Alzheimer disease experienced a weight loss of 5% compared with control subjects. These investigators suggested that Alzheimer disease patients may be characterized by dysfunction in body weight regulation. Wolf-Klein et al (15) examined 13 Alzheimer disease patients and 44 control subjects for 1 y and found that 92% of the Alzheimer disease patients lost weight, whereas only 39% of the control subjects lost significant amounts of weight (15). Berlinger and Potter (16) did not assess weight change in Alzheimer disease patients, but did find that patients with dementia had a body mass index that was 10% lower than that of older, healthy volunteers. Alzheimer disease patients were also shown to have less fat-free mass than age-matched, healthy elderly subjects, as measured by bioelectrical impedance (17).

A decline in body weight may be due to low energy intakes in Alzheimer disease patients. Thus, several investigators examined the adequacy of diets offered to patients and found energy intakes to be adequate, whereas others found that diets were suboptimal (10, 18–20). These contradictory results are not surprising because the instruments available for measuring energy intake are imprecise and likely do not represent free-living feeding patterns or habitual energy intake (21). Other investigators found that weight loss was correlated with decreased independence in self-feeding (22) and that weight loss was coincident with nursing home placement. These investigators suggested that weight loss is a consequence of Alzheimer disease and does not reflect specific brain lesions. However, Grundman et al (23) showed a significant association between low body weight and atrophy of the mesial cortex, a region of the central nervous system involved in the control of feeding behavior, thus establishing a morphologic basis for the association between central nervous system pathology and weight loss in Alzheimer disease patients.

Recently, an interesting observation was made by Olin et al (24), who reported increased energy intake (and increased body mass) in elderly patients who were fed either a high-energy diet or a diet of the same volume but with a lower energy content. These investigators suggested that it is the volume of food that is the primary determinant of energy intake in elderly individuals, and that it may be possible to increase energy intakes in these individuals by increasing the energy density of their diet. The results of this study have important implications for individuals with Alzheimer disease. Because Alzheimer disease patients suffer from symptoms such as confusion, loss of memory, apraxia, and anosmia, it seems safe to assume that the volume of food is also one of the factors determining energy intake in Alzheimer disease patients. Thus, it may be possible to increase food intake in Alzheimer disease patients by increasing the energy density of their food. This nutritional strategy is feasible in both institutionalized and noninstitutionalized patients.

IS ALZHEIMER DISEASE ASSOCIATED WITH ABNORMALLY HIGH ENERGY EXPENDITURE?  
It has been suggested that Alzheimer disease is associated with a hypermetabolic state, which may result in weight loss (25). That is, high energy expenditures that are not matched by energy intake may contribute to involuntary weight loss in Alzheimer disease patients. High energy expenditures could be caused, for example, by increased physical activity levels (eg, excessive pacing) or by increased energy needs for a given metabolic size. Unlike the assessment of food intake, the measurement of energy expenditure in humans is reliable and accurate and when used in combination with sophisticated measurements of body composition can indicate the presence or absence of abnormally high energy expenditures.

The resting metabolic rate (RMR) is the largest portion of total daily energy expenditure (60–75%) and represents the energy expended for the maintenance of normal body functions and homeostasis (Figure 1). These processes include the energy cost of resting cardiovascular and pulmonary functions, the energy consumed by the central nervous system, the energy needed to maintain cellular homeostasis, and other biochemical reactions involved in the maintenance of bodily functions. RMR is primarily related to the magnitude of the fat-free mass in the body and is also influenced by age, sex, body composition, and genetic factors (26). Small perturbations in RMR theoretically would have a significant effect on the regulation of body weight in Alzheimer disease patients.

View larger version (26K):
FIGURE 1. . The components of total daily (24 h) energy expenditure.

 
Several investigators examined whether RMR was higher in Alzheimer disease patients than in healthy elderly subjects. The most meaningful comparison is to examine the RMR in 2 groups matched for fat-free mass or after statistical control for this component (27). In carefully performed studies, no convincing evidence was found that RMR was higher in Alzheimer disease patients than in healthy elderly subjects. For example, Niskanen et al (28) found that RMR was similar in 10 patients with Alzheimer disease (4555 ± 540 kJ/d) and 10 age-matched control subjects (4969 ± 598 kJ/d). Other investigators found that RMR was higher in Alzheimer disease patients than in control subjects when the measurement was normalized for body weight but not for the quantity of fat-free mass (29). The small sample size in these aforementioned studies, however (5 Alzheimer disease patients and 5 control subjects), precludes firm conclusions. Our laboratory found no significant differences in RMR adjusted for fat-free mass, fat mass, and age between 25 Alzheimer disease patients (5496 ± 561 kJ/d) and 75 healthy elderly subjects (5614 ± 623 kJ/d) (30). The large sample size and the use of dual-energy X-ray absorptiometry to measure body composition lend validity to these findings. Although 2 other studies did not directly compare RMRs between Alzheimer disease patients and healthy elderly subjects (31, 32), they found that the mean RMR in demented patients was lower than that predicted from standard equations based on data from healthy elderly subjects.

The thermic effect of feeding is defined as the increase in energy expenditure associated with food ingestion. This component represents 10% of the total daily energy expenditure and includes the energy costs of food absorption, metabolism, and storage (Figure 1). The magnitude of the thermic effect of feeding depends on several factors, including the energy content and the composition of the meal as well as the antecedent diet of the individual. After meal ingestion, energy expenditure increases for 4–8 h, its magnitude and duration depending on the quantity and type of macronutrient (ie, protein, fat, or carbohydrate) consumed. To our knowledge, no studies have examined the thermic effect of feeding in Alzheimer disease patients.

In our opinion, previous methodologic problems have limited the rigorous examination of energy metabolism in Alzheimer disease patients (26). The use of the doubly labeled water method, indirect calorimetry, and sophisticated body-composition methods makes it possible to precisely measure energy expenditure and the components of body composition with noninvasive techniques and minimal cooperation from the volunteers. These methodologic tools can convincingly provide the needed information to examine the existence or absence of a "disturbed" energy balance regulation in Alzheimer disease patients. To show a hypermetabolic state in Alzheimer disease patients, it would be necessary to accurately measure total daily energy expenditure and its components (RMR and physical activity) and thereafter show that energy expenditure values are indeed higher after the data are normalized for differences in body composition. This is because thermogenesis is a function of the metabolically active cell mass; therefore, a patient's energy expenditure must be evaluated relative to specific body-composition compartments and not just relative to total body weight.

The doubly labeled water technique (²H₂¹⁸O) is a fairly new method that has been used to measure total daily energy expenditure in free-living humans (33). This technique provides a measure of free-living energy expenditure. Because it is ultimately the balance between both total daily energy intake and total daily energy expenditure that regulates body composition in Alzheimer disease patients, this method can provide evidence for or against the hypothesis that Alzheimer disease patients are hypermetabolic. The main advantages of the doubly labeled water method are as follows: 1) it is noninvasive and requires only minimal cooperation from the volunteers, 2) it can be used over extended periods of time in free-living individuals (1–3 wk), and 3) it provides an integrated measurement of all 3 components of total daily energy expenditure (RMR, the thermic effect of feeding, and physical activity energy expenditure).

We examined total daily energy expenditure and body composition in 30 Alzheimer disease patients aged 73 ± 8 y and in 103 healthy elderly subjects aged 69 ± 7 y by using the doubly labeled water method (34). Our Alzheimer disease patients had a wide range of scores (0–24) on the Mini-Mental State Examination (35). Patients were ambulatory and living at home with their family or caregiver. As presented in Table 1, Alzheimer disease patients had a lower body mass (NS), primarily because of a lower fat-free mass. Total daily energy expenditure was assessed over 10 d with the doubly labeled water method. RMR and body composition were assessed after an overnight fast in which patients and their caregivers slept overnight in the General Clinical Research Center. We found that the physical presence of the caregiver exerted a calming influence on the Alzheimer disease patients. Thereafter, measurements of RMR and body composition by dual-energy X-ray absorptiometry could be performed with minimal movement and little agitation of the patient.

View this table:
TABLE 1.. Physical characteristics of Alzheimer disease patients and healthy elderly individuals¹  
Total daily energy expenditure and its components in Alzheimer disease patients and control subjects are shown in Table 2. Total daily energy expenditure was 14% lower in Alzheimer disease patients because of a 9% lower RMR and a 26% lower physical activity energy expenditure. Because Alzheimer disease patients had a lower fat-free mass ( ± SD: 45 ± 9 kg) than did the healthy elderly subjects (49 ± 8 kg) and because fat-free mass is an important determinant of individuals' differences in energy expenditure, we examined the components of total daily energy expenditure after statistically controlling for fat-free mass by analysis of covariance. No significant differences in adjusted RMR (5660 ± 669 compared with 5898 ± 632 kJ/d) or physical activity energy expenditure (2133 ± 1472 compared with 2347 ± 1422 kJ/d) were found between Alzheimer disease patients and healthy elderly subjects, respectively. We also explored the possibility that a subgroup of cachectic Alzheimer disease patients who had shown substantial body weight loss (5.6 ± 2.3 kg) would exhibit high energy expenditures. The cachectic patients, however, showed no evidence of a hypermetabolic state. These findings are supported by the work of Prentice et al (31), who reported similar results and found no evidence of hypermetabolism or hyperactivity in 5 demented patients with probable Alzheimer disease or 4 depressed patients. It should be kept in mind, however, that we examined noninstitutionalized Alzheimer disease patients who probably were receiving optimal care at home by their caregiver or spouse. Thus, our results cannot be extrapolated to institutionalized patients, whose care may be suboptimal.

View this table:
TABLE 2.. Daily energy expenditure and its components in Alzheimer disease patients and healthy elderly individuals¹  
Physical activity energy expenditure represents the energy expended above the RMR and the thermic effect of feeding and includes the energy expended through voluntary exercise plus the energy devoted to involuntary activity such as shivering, fidgeting, and postural control. Physical activity represents an important factor governing the daily energy expenditure in humans because it is extremely variable and subject to voluntary control. This component of total daily energy expenditure may be substantially elevated in Alzheimer disease patients who display wandering or pacing behavior and thus may contribute to the abnormally elevated total daily energy expenditure in these individuals. In our own work, we found that physical activity energy expenditure was actually lower (P < 0.05) in 30 Alzheimer disease patients (1777 ± 1326 kJ/d) than in 103 healthy elderly subjects (2401 ± 1430 kJ/d) when measured with the doubly labeled water method. This suggests that the physical activity component of total daily energy expenditure was not responsible for the unexplained weight loss in Alzheimer disease patients (34).

Low physical activity levels were shown to predict cardiovascular disease risk in healthy older individuals (36). Therefore, because Alzheimer disease patients actually have lower levels of physical activity energy expenditure than do healthy elderly individuals, it is important to examine factors that may be related to low physical activity energy expenditure. We reported previously that physical activity energy expenditure was significantly correlated with appendicular skeletal muscle mass (Figure 2) and energy intake (Figure 3) in a cohort of 30 noninstitutionalized Alzheimer disease patients (37).

View larger version (18K):
FIGURE 2. . Relation between physical activity energy expenditure and appendicular skeletal muscle mass in Alzheimer disease patients.

 

View larger version (15K):
FIGURE 3. . Relation between physical activity energy expenditure and energy intake in Alzheimer disease patients.

 
The association between physical activity energy expenditure and appendicular skeletal muscle mass may be explained, at least in part, by the hypothesis that physical activity may provide the necessary stimulation to prevent the skeletal muscle loss frequently observed in Alzheimer disease. Although a cause and effect relation cannot be inferred from cross-sectional data, this hypothesis is partially supported by the findings of Starling et al (38), who showed that physical activity energy expenditure was positively related to fat-free mass in a large sample of older, healthy, white men and women. Thus, higher levels of physical activity energy expenditure in both Alzheimer disease patients and healthy elderly individuals may be associated with greater skeletal muscle mass. Maintenance of skeletal muscle mass in Alzheimer disease patients is of significant clinical importance because the loss of skeletal muscle mass contributes to decreased muscular strength (39) and increased frequency of falls and is also one of the major factors contributing to the loss of functional independence and ultimately mortality (9, 10). Thus, physical activity may represent a simple intervention to offset unwanted loss of skeletal muscle mass in Alzheimer disease patients.

Another variable found to be associated with physical activity energy expenditure was energy intake (r = 0.42). This notion may be partially explained by the hypothesis that physical activity stimulates energy intake through improved matching of energy intake to energy expenditure. This hypothesis is supported by intervention studies in older healthy individuals. Poehlman et al (40) showed that a moderate increase in physical activity (3.8 MJ/wk) caused a compensatory and proportional increase in energy intake in older individuals. Furthermore, Bunyard et al (41) reported recently that aerobic exercise intervention increased energy intake in middle-aged men. Thus, it seems plausible to suggest that physical activity may provide physiologic cues that stimulate energy intake and thus restore energy balance in Alzheimer disease patients. This hypothesis needs to be examined in future intervention studies.

Taken together, these findings provide no evidence of a hypermetabolic state in Alzheimer disease patients. In fact, these results suggest that measured rates of resting and physical activity energy expenditure are generally lower in Alzheimer disease patients because these individuals are usually small and have less metabolically active tissue (eg, fat-free mass). Further studies need to be performed in Alzheimer disease patients in whom energy expenditure is measured during the dynamic phase of weight loss. Interestingly, the notion that abnormally high energy expenditure levels contribute to unexplained weight loss has been challenged by data from our laboratory in other neurologic (42) and cardiovascular (43) diseases.

PREDICTION OF DAILY ENERGY NEEDS IN ALZHEIMER DISEASE PATIENTS  
Although there is a clear need to provide Alzheimer disease patients with well-founded recommendations for dietary intake, there have been major technical, physiologic, and conceptual problems in doing so. The establishment of individual energy requirements has been problematic because 1) the calculation of energy intakes from self-recorded diaries or dietary interviews, which are known to be inaccurate; 2) the use of multiple measures of basal metabolic rate (or RMR) to predict energy needs; and 3) the failure of current recommended daily energy requirements to account for the diversity of disease state, body composition, and physical activity in the elderly. The measurement of daily energy expenditure has been suggested as a proxy measure of daily energy needs when individuals are generally in energy balance (21, 44).

We attempted to predict the daily energy needs of Alzheimer disease patients by measuring free-living total daily energy expenditure in 30 individuals (17 women and 13 men) with Alzheimer disease (45). We measured total daily energy expenditure with the doubly labeled water method and body composition with dual-energy X-ray absorptiometry. RMR, fat-free mass, fat mass, and body weight were examined as possible correlates of total daily energy expenditure because of the previously reported association of these variables with total daily energy expenditure (38). Stepwise regression analysis was used to identify the best model to predict total daily energy expenditure. Correlation analysis identified RMR, fat-free mass, and body weight as the variables significantly associated with total daily energy expenditure. Thereafter, we used these 3 variables as the independent variables in the stepwise regression procedure, with total daily energy expenditure as the dependent variable. We obtained the following equation (steps not shown in table form):

CONCLUSION  
There is no compelling evidence that energy expenditure is abnormally elevated relative to body size in Alzheimer disease patients. We suggest that future studies examine the dietary and physical activity behavior of Alzheimer disease patients with the goal of developing intervention strategies to restore energy balance and maintain skeletal muscle mass. This is particularly important because nutritional and physical activity interventions may represent practical and inexpensive strategies in the therapeutic management of Alzheimer disease patients.

REFERENCES  

1. US Congress, Office of Technology Assessment. Confused and burdened families: finding help for people with Alzheimer's disease and other dementias. Washington, DC: US Government Printing Office, 1990.
2. Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported. JAMA 1989;262:2551–6.
3. Pfeffer RI, Afifi AA, Chance JM. Prevalence of Alzheimer's disease in a retirement community. Am J Epidemiol 1987;125:420–36.
4. Rocca WA, Amaducci LA, Schoenberg BS. Epidemiology of clinically diagnosed Alzheimer's disease. Ann Neurol 1986;19:415–24.
5. US Bureau of Census. Projections estimated from Current Population Survey. Washington, DC: US Government Printing Office, 1987.
6. Katzman R. Editorial: the prevalence and malignancy of Alzheimer disease. A major killer. Arch Neurol 1976;33:217–8.
7. Folstein MF, Whitehouse PJ. Cognitive impairment of Alzheimer disease. Neorobehav Toxicol Teratol 1983;5:631–4.
8. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939–44.
9. Pinchcofsky-Devin GD, Kaminski MV Jr. Correlation of pressure sores and nutritional status. J Am Geriatr Soc 1986;34:435–40.
10. Sandman PO, Adolfsson R, Nygren C, Hallmans G, Winblad B. Nutritional status and dietary intake in institutionalized patients with Alzheimer's disease and multiinfarct dementia. J Am Geriatr Soc 1987;35:31–8.
11. Singh S, Mulley GP, Losowsky MS. Why are Alzheimer patients thin? Age Ageing 1988;17:21–8.
12. Burns A, Marsh A, Bender DA. Dietary intake and clinical, anthropometric and biochemical indices of malnutrition in elderly demented patients and non-demented subjects. Psychol Med 1989;19:383–91.
13. Goodwin JS, Goodwin JM, Garry PJ. Association between nutritional status and cognitive functioning in a healthy elderly population. JAMA 1983;249:2917–21.
14. White H, Pieper C, Schmader K, Fillenbaum G. Weight change in Alzheimer's disease. J Am Geriatr Soc 1996;44:265–72.
15. Wolf-Klein GP, Silverstone FA, Levy AP. Nutritional patterns and weight change in Alzheimer patients. Int Psychogeriatr 1992;4:103–18.
16. Berlinger WG, Potter JF. Low body mass index in demented outpatients. J Am Geriatr Soc 1991;39:973–8.
17. Elmstahl A, Petersson M, Lilja B, Samuelsson SM, Rosen I, Bjuno L. Body composition in patients with Alzheimer's disease and healthy controls. J Clin Exp Gerontol 1992;14:17–31.
18. Parvizi S, Nymon M. A dietary study of elderly nursing home residents in Fargo, North Dakota. J Nutr Elderly 1982;2:15–9.
19. Bucht G, Sandman PO. Nutritional aspects of dementia, especially Alzheimer's disease. Age Ageing 1990;19:S32–6.
20. Renvall MJ, Spindler AA, Ramsdell JW, Paskvan M. Nutritional status of free-living Alzheimer's patients. Am J Med Sci 1989;298:20–7.
21. Schoeller DA. How accurate is self reported energy intake? Nutr Rev 1990;48:373–9.
22. Du W, DiLuca C, Growdon JH. Weight loss in Alzheimer's disease. J Geriatr Psychiatry Neurol 1993;6:34–8.
23. Grundman M, Corey-Bloom J, Jernigan T, Archibald S, Thal LJ. Low body weight in Alzheimer's disease is associated with mesial temporal cortex atrophy. Neurology 1996;46:1585–91.
24. Olin AO, Osterberg P, Hadell K, Armyr I, Jerstrom S, Ljungqvist O. Energy-enriched hospital food to improve energy intake in elderly patients. JPEN J Parenter Enteral Nutr 1996;20:93–7.
25. Adolfsson R, Bucht G, Lithner F, Winblad B. Hypoglycemia in Alzheimer's disease. Acta Med Scand 1989;208:387–8.
26. Poehlman ET. Regulation of energy expenditure in aging humans. J Am Geriatr Soc 1993;41:552–9.
27. Poehlman ET, Toth MJ. Mathematical ratios lead to spurious conclusions regarding age- and sex-related differences in resting metabolic rate. Am J Clin Nutr 1995;61:482–5.
28. Niskanen L, Piirainen M, Koljonen M, Uusitupa M. Resting energy expenditure in relation to energy intake in patients with Alzheimer's disease, multi-infarct dementia and in control women. Age Ageing 1993;22:132–7.
29. Wolf-Klein GP, Silverstone FA, Lansey SC, et al. Energy requirements in Alzheimer's disease patients. Nutrition 1995;11:264–8.
30. Donaldson KE, Carpenter WH, Toth MJ, Goran MI, Newhouse P, Poehlman ET. No evidence for a higher resting metabolic rate in noninstitutionalized Alzheimer's disease patients. J Am Geriatr Soc 1996;44:1232–4.
31. Prentice AM, Leavesley K, Murgatroyd PR, et al. Is severe wasting in elderly mental patients caused by an excessive energy requirement? Age Ageing 1989;18:158–67.
32. Wang SY, Fukagawa N, Hossain M, Ooi WL. Longitudinal weight changes, length of survival, and energy requirements of long-term care residents with dementia. J Am Geriatr Soc 1997;45:1189–95.
33. Schoeller DA, Ravussin E, Schutz Y, Acheson KJ, Baertschi P, Jequier E. Energy expenditure by doubly labeled water: validation in humans and proposed calculation. Am J Physiol 1986;250:E66–72.
34. Poehlman ET, Toth MJ, Goran MI, Carpenter WH, Newhouse P, Rosen CJ. Daily energy expenditure in free-living non-institutionalized Alzheimer's patients: a doubly labeled water study. Neurology 1997;97:997–1002.
35. Folstein MF, Folstein SE, Mchugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189–98.
36. Poehlman ET, Toth MJ, Bunyard LB, et al. Physiological predictors of increasing total and central adiposity in aging men and women. Arch Intern Med 1995;155:2443–8.
37. Dvorak RV, Poehlman ET. Appendicular skeletal muscle mass, physical activity, and cognitive status in patients with Alzheimer's disease. Neurology 1998;51:1386–90.
38. Starling RD, Toth MJ, Carpenter WH, Matthews DE, Poehlman ET. Energy requirements and physical activity in free-living older women and men: a doubly labeled water study. J Appl Physiol 1998; 85:1063–9.
39. Larsson L, Grimby G, Karlsson J. Muscle strength and speed of movement in relation to age and muscle morphology. J Appl Physiol 1979;46:451–6.
40. Poehlman ET, Gardner AW, Goran MI. Influence of endurance training on energy intake, norepinephrine kinetics, and metabolic rate in older individuals. Metabolism 1992;41:941–8.
41. Bunyard LB, Katzel LI, Busby-Whitehead J, Wu Z, Goldberg AP. Energy requirements of middle-aged men are modifiable by physical activity. Am J Clin Nutr 1998;68:1136–42.
42. Toth MJ, Fishman PS, Poehlman ET. Free-living daily energy expenditure in patients with Parkinson's disease. Neurology 1997;97:88–91.
43. Toth MJ, Gottlieb SS, Goran MI, Fisher ML, Poehlman ET. Daily energy expenditure in free-living heart failure patients. Am J Physiol 1997;272:E469–75.
44. Roberts SB. Energy requirements of older individuals. Eur J Clin Nutr 1996;50(suppl 1):S112–7.
45. Poehlman ET, Dvorak RV. Energy expenditure in Alzheimer's disease. J Nutr Health Aging 1998;2:115–8.