A study of the nutritional status of elderly patients with Parkinson's disease

Keren N. Davies

Introduction

Elderly patients with Parkinson's disease (PD) often lose weight. This not only adds to the morbidity of the parkinsonian patient (1) but undernutrition per se results in increased mortality (2, 3). The reasons for the weight loss have been little studied. Two studies have suggested an increase in energy expenditure (4)(5), other possible causes include dietary deficiency (6), malabsorption due to small-bowel bacterial overgrowth (7-9) and the presence of a circulating factor, e.g. tumour necrosis factor (10, 11). We studied a group of patients with PD who had lost weight to determine whether they showed evidence of undernutrition and to assess possible aetiological factors.

Methods

Fifteen patients (nine women, median age 73.9 years, range 68.3-80.5 years) with PD who had weight loss documented in the medical notes, of at least 5 kg in the previous 12 months and 15 age- and sex-matched healthy control subjects (median age 73.6, range 67.6-80.3 years) were studied. The control subjects were randomly selected from general practice registers and luncheon clubs for older people. Eleven of the 15 patients were living with their spouse, three lived alone and one was resident in a nursing home. Nine of the control subjects lived alone, the remainder with their spouse.

Ethical approval was obtained from the Wirral Health Authority ethics committee. All subjects gave written informed consent.

All PD patients had at least two of the triad of tremor, rigidity and bradykinesia. All the patients were taking L-dopa to which they had had a good response. Their condition and medication had been stable for at least 6 months prior to study. Patients were excluded if they had swallowing disorders, gastro-intestinal disorder or malabsorption, metabolic disease, e.g. diabetes, thyrotoxicosis or other chronic disorders known to cause weight loss, e.g. chronic cardiac failure. PD was graded with the Hoehn and Yahr scale (12), and the Nottingham activities of daily living (ADL) scale (13) was completed for each patient. Disease duration and total daily dose of L-dopa were recorded. All the controls were screened, healthy elderly people on no medication. All tests were carried out by one of two investigators (K.D. or D.K.).

Anthropometric measurements: Height and weight were recorded and body mass index (BMI) was calculated as the ratio of weight (kg) to height [(m).sup.2]. Skin-fold thickness measurements were made at four standard sites (triceps, biceps, subscapular and supra-iliac) using Harpenden calipers. Three recordings were taken from each site and the mean recorded. Mid-arm circumference (MAC) was measured at the mid-point between the olecranon and acromion process. Body fat was estimated by the method of Durnin and Womersley (14). Arm muscle circumference (AMC) was calculated according to the formula AMC = MAC - (TSF x 0.314) where TSF is triceps skin-fold thickness.

Biochemical and haematological tests: Fasting blood samples were taken for albumin, calcium, serum alkaline phosphatase, total protein, urea, electrolytes and glucose (Excel analyser Indianapolis, USA), haemoglobin, MCV, total peripheral lymphocyte count (TPLC) (Bayer diagnostic technicon counter), ferritin (immuno-radiometric assay, IDS Ltd, Washington, Newcastle) red cell folate and serum [B.sub.12] (Biorad Quantaphase, radio-isotope dilution assay, Biorad Laboratories Ltd, Watford Hertfordshire) and thyroid function tests (immuno-radiometric assay, IDS Ltd). All these samples were analysed in one hospital laboratory.

Tumour necrosis factor: Plasma TNF was measured by indirect sandwich ELISA (15). Polyvinyl plates (Dynatech) were coated with an anti-human TNF alpha monoclonal antibody at 10 [micro]g/ml in 0.05 M sodium buffer, pH 9.6 for 16 h at 22[degrees]C. Plates were then washed in phosphate buffered saline plus 0.05% Tween-20(PBS Tween). After being blocked with 1% skimmed milk powder for 1 h and washed with PBS Tween, TNF alpha standards were added together with the samples at 1/100 dilution in 1% skimmed milk. The plates were incubated for 2 h at 22[degrees]C. Following washing with PBS Tween, a rabbit anti-serum against human TNF alpha was added at a dilution of 1/100 in 1% skimmed milk and incubated for 1 h at 22[degrees]C. After washing, peroxidase conjugated sheep anti-rabbit immunoglobulin (Silenus) was added at 1/5000 in 1% skimmed milk and incubated for 45 min at 22[degrees]C. Plates were washed again then incubated at 22[degrees]C with the peroxidase substrate, 0.03 mg/ml of 2,2-azino-di (3-ethyl-benzthiazidine sulphonate) in 0.1 M citrate buffer, pH 4, containing 0.02% hydrogen peroxide. The colour change was monitored at 405 nM using a Titertek Multiscan autoreader.

Dietary assessment: All subjects were interviewed by a dietitian and shown how to complete a dietary diary, using common household measures, e.g. teacups, tablespoons, to quantify food consumed. A 7-day diary was completed. The completeness of the diary was checked and any necessary supplementary information obtained by the dietitian at the end of the 7-day period. The data were analysed for mean daily intake of calories, protein, fat, carbohydrate, vitamins and trace elements by Compudiet (Scientific Hospital Supplies, Liverpool--software based on McCance and Widdowson's nutritional tables (16)).

Data are expressed as mean ([+ or -] SEM) or median and range. Statistical analysis was performed using the Mann-Whitney U test for non-parametric data, Student's t test for normally distributed data and Spearman's rank correlation where appropriate. A significance level of 5% was defined.

Results

The PD patients had a mean disease duration of 7.3 years (range 1-16 years). Median daily dose of L-dopa was 450mg (range 150-1250mg). There was a variation in disease severity between Hoehn and Yahr grades 1 to 5 (60% grade 3) and the Nottingham ADL score between 3 and 10.

Anthropometric measurements: The PD patients had lost a mean of 6.2kg (range 5-10.1kg). The PD patients weighed less than the controls [mean 61.4(4.1) vs. 71.1 (4.6)kg, p = 0.05]. There were no significant differences between data from men and women in the study and therefore the data are pooled.

TSF thickness [10.7 (1.2) vs. 24.5 (3) mm, p < 0.0001], body fat [16.9 (1.5) vs. 28 (2.6) kg, p < 0.001] and percentage body fat [27.5 (1.6) vs. 38.9 (1.7)%, p < 0.0001] were reduced significantly in the PD patients. FFM and AMC did not differ significantly between the groups (Table I).

Table I. Anthropometric measurement results in Parkinson's disease patients (PD) and control subjects

                    PD           Controls       p value
                   (n = 15)       (n = 15)          of
                 Mean (SE)      Mean (SE)      difference
Weight (kg)      61.4(4.1)      71.1(4.6)       0.05
Height (m)        1.61(0.4)      1.64(0.4)        NS
BMI              23.5(1.1)      26.1(1.3)         NS
AMC (cm)         22.5(0.7)      22.2(1.0)         NS
TSF (mm)         10.7(1.2)      24.5(3)        < 0.0001
FFM (kg)         44.5(3)        43.1(3)           NS
% Fat            27.5(1.6)      38.9(1.7)      < 0.0001
Body fat (kg)    16.9(1.5)      28(2.6)        < 0.001

BMI = body mass index; AMC = arm muscle circumference;

TSF = triceps skin-fold thickness; FFM = fat-free mass.

Biochemical and haematological tests: There was a lower peripheral lymphocyte count [mean 1.4 x [10.sup.9]/l (0.1) vs. 1.8 x [10.sup.9]/l(0.1), p < 0.01] and serum [B.sub.12] [mean 274 (28) vs. 440 ng/l (50), p = 0.004] in the patients. There were no significant differences in haemoglobin, MCV, ferritin, red cell folate, serum albumin, total protein, corrected calcium, alkaline phosphatase, urea, creatinine or electrolytes. All fasting blood glucose measurements and thyroid function tests were normal.

Tumour necrosis factor: TNF was not detected in any of the patients or controls.

Dietary data: The PD patients had a higher mean daily calorie intake [2247 (131) vs. 1809 (153) kcal/day, p = 0.02] which was derived from increased carbohydrate in their diet (Table II). There was no correlation between disease severity (Hoehn and Yahr score) and daily calorie intake for the patients. Other significant dietary differences were the increased fibre intake [24 (2) vs. 16 (2) g, p < 0.01], vitamin C intake [80 (12) vs. 45 (7) mg, p = 0.004] and folate intake [171 (13) vs. 123 (13) [micro]g, p < 0.01] in the PD patients (Table II). No patient was consuming any dietary supplements, or receiving Meals-on-Wheels. Alcohol consumption was negligible in both groups. Table II. Mean daily dietary intake in Parkinson's disease (PD) and control subjects

                       PD         Controls   p value
           (n = 15)               (n = 15)      of
                   Mean (SE)    Mean (SE)   difference

Mean daily intake
Calories (kcal)    2247 (131)   1809 (153)      0.02
Protein (g)          74 (4.6)     68 (5.6)      NS
CHO (g)             299 (20)     221 (19)     < 0.005
Fat (g)              89 (6)       76 (7)        NS
Fibre (g)            24 (2)       16 (2)      < 0.01
Vitamin C (mg)       80 (12)      45 (7)        0.004
Folate ([micro]g)   171 (13)     123 (13)     < 0.01

Discussion

Parkinson's disease may result in undernutrition (6). The reason for this is not fully understood but is likely to be multifactorial. Previous studies have shown increased resting energy expenditure (4)(5) which is undoubtedly a factor. Levi et al. (4) measured resting energy expenditure in parkinsonian patients before and after their usual medication. All showed an increased resting energy expenditure with little change following medication in most of the patients. However some patients developed involuntary movements following medication and showed a further increase in energy expenditure, while patients developing a hypertonic state showed a decrease. Markus et al. (5) confirmed that resting energy expenditure was increased in patients with Parkinson's disease before and after treatment with apomorphine. They found that energy expenditure was significantly higher in the untreated state for a subgroup of patients showing marked rigidity relieved by apomorphine. Patients developing dyskinetic movements in the treated state showed a further increase in energy expenditure. These studies used different methods but imply that total energy expenditure may vary considerably from day to day and with medication. The effect of exercise on energy expenditure in PD patients is unknown, but their capacity for exercise is often restricted and may in fact reduce their expenditure.

We have shown that patients with PD who have lost weight and exhibit a calorie (body fat) rather than protein (lean body mass) undernutrition have an adequate daily intake of calories and vitamins. Yapa et al. (6) in an uncontrolled study of nutritional status of patients with PD obtained similar measurements of TSF and AMC but did not determine FFM or body fat. They showed that values were significantly lower than expected when compared with normal predicted values for elderly subjects. Although the TSF thickness and BMI were higher than might be expected in the control group none of the anthropometric measurements showed a significant difference from reference values for elderly subjects (17)(18). Yapa et al. (6) concluded that male patients showed evidence of protein/calorie depletion, because of reduced TSF and AMC measurements, while female patients showed calorie malnutrition, reduced TSF measurements only, and suggested the deficiencies may be due to the disease process or dietary deficiency. We have shown that the patients' mean total daily calorie intake was significantly higher than the controls' and higher than the recommended daily allowance (RDA) (19). The extra calorie intake was derived from a significantly higher carbohydrate intake both in grams ingested and percentage of diet made up of carbohydrate. In keeping with the high dietary intake of carbohydrate the PD patients had high intakes of fibre, vitamin C and folate.

A number of studies have suggested that small-bowel bacterial overgrowth is implicated in malabsorption in elderly subjects even when the small bowel is anatomically normal (7)(20). It has been suggested that small-bowel bacterial contamination may result from ageing alone (20), achlorhydria with or without pernicious anaemia (7)(21) and reduced intestinal motility (21). Although the PD patients had significantly lower [B.sub.12]. levels none had evidence of pernicious anaemia. We have found a prolonged orocaecal transit time in patients with PD without evidence of small-bowel bacterial overgrowth [unpublished data].

The total peripheral lymphocyte count was significantly lower in the PD patients than in the controls. Changes in the immune system with ageing have been described yet are difficult to separate from the effects of associated medical conditions (22). Immunological studies of patients with protein calorie malnutrition have shown depressed lymphocyte counts, which are restored by dietary repletion (23). Although the PD patients only showed evidence of calorie malnutrition the change in TPLC suggests that immunological changes have occurred and the malnourished patients may be more susceptible to infections with consequent increases in morbidity and mortality. TNF (cachexin) is produced by monocytes in response to endotoxin and other membrane products and it has been suggested as the cause of metabolic abnormalities accompanying malignant neoplasms leading to cachexia (24). Elevated levels have subsequently been demonstrated in a variety of conditions including a variety of neoplasms (25), chronic heart failure (26)(27), chronic parasitic infections and acquired immunodeficiency syndrome (26) all characterized by anorexia and weight loss. In this small study we found no evidence of TNF contributing to weight loss in PD patients.

Patients with PD who lose weight show evidence of calorie malnutrition in spite of an increased calorie intake. Despite the patients being well controlled on medication we postulate that weight loss is due to an increase in metabolic rate or altered muscle metabolism.

Acknowledgement

We would like to thank Nicholas Laboratories, Roche Products Ltd, Broadwater Rd, Welwyn Garden City, Hertfordshire for supporting this study, Dr J. A. Barrett for allowing us to study his patients, and Mrs Linda Edward for her help with the dietary data.

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Authors' addresses(*)

Department of Medicine for the Elderly,

Clatterbridge Hospital, Wirral L63 4JY, and

Department of Immunology, University of Liverpool (*)Address correspondence to Dr Keren Davies, Department of Health Care for the Elderly, Royal London Hospital (Mile End), Bancroft Road, London E1 4DG

Received in revised form 22 June 1993

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