DEPENDENCE OF THE GERIATRIC DEPRESSION SCORES ON AGE, NUTRITIONAL STATUS, AND HAEMATOLOGIC VARIABLES IN ELDERLY INSTITUTIONALIZED PATIENTS

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1 08 ALVES DE REZENDE/c:04 LORD_c 8/10/09 11:41 Page 617 DEPENDENCE OF THE GERIATRIC DEPRESSION SCORES ON AGE, NUTRITIONAL STATUS, AND HAEMATOLOGIC VARIABLES IN ELDERLY INSTITUTIONALIZED PATIENTS C.H. ALVES DE REZENDE 1, L.M. COELHO 1, L.M. OLIVEIRA 1, N. PENHA-SILVA 2 1. Faculty of Medicine, Federal University of Uberlândia, , Uberlândia, Minas Gerais, Brazil; 2. Institute of Genetics and Biochemistry, Federal University of Uberlândia, , Uberlândia, Minas Gerais, Brazil. Corresponding author: N. Penha-Silva, Institute of Genetics and Biochemistry, Federal University of Uberlândia, Uberlândia, MG, Brazil, Phone (55) , ext. 23, Fax (55) , ext. 24, nspenha@ufu.br Abstract: Objective: To evaluate the relationships between depression and ageing, nutrition, and selected haematologic variables. Measurements: A cross-sectional study was performed in elderly institutionalized patients (n=100) of all nursing homes in the Brazilian city of Uberlândia, with determination of the Geriatric Depression Scale (GDS) and the Mini-Nutritional Assessment (MNA) scores, and selected haematologic variables. Results: GDS had a significant negative dependence with the MNA for the entire institutionalized population. The prevalence of depression was higher among females, but significant correlations existed between GDS scores and erythrocytes counts, haemoglobin levels, or haematocrit values for the males only. However, a borderline correlation existed between GDS and the mean corpuscular volume (MCV) values in the females. Conclusions: Depression was associated with worsening of nutritional status and the degree of anemia of the entire elderly population and the male, but not the female subjects. The borderline correlation observed between the GDS and MCV for the female subjects suggests that the nutritional deficiencies responsible for the MCV increase are a cause, and not an effect, of depression. Key words: Depression, geriatric depression scale, nutritional status, mini-nutritional assessment, haematologic variables. Introduction Depression is a very serious problem worldwide, with a large prevalence among the elderly population, where it is particularly associated with nutritional status. Elderly depression is considered a psychologic phenomenon with nutritional consequences or a nutritional problem with psychological implications. Discussion about this dualism may help to understand the interrelationships between psychology and nutrition. If depression is a cause, the consequence will be a general malnutrition condition, although the reciprocal would also be true. However, if depression is associated specifically with malnutrition, it would be a consequence rather than a cause of the nutritional deficiency. Specific nutritional deficiencies, particularly folate and cobalamine, have been reported (1-3), especially in the elderly population, where they have been attributed to factors, such as feeding limitations, institutionalization, loss of appetite, reduction in absorption, medicine use and abuse, and diseases, such as dementia and depression (4-6). As low folate and cobalamine levels are prevalent in elders with psychiatric disorders, such as depression, although they also appear in the healthy (6, 7); it seems that these deficiencies can be seen as nutritional causes of depression. Folate and cobalamine participate in the remethylation of homocysteine (Hcy) to produce the amino acid methionine. Since the only endogenous source of homocysteine in our organism is methionine, deficiencies of folate and/or cobalamine are known causes of hyperhomocysteinemia (8, 9). High blood levels of Hcy have been associated with several neuropsychiatric disorders, such as depression, schizophrenia, Alzheimer s disease, and Parkinson s disease (10). It may be consequence of the toxicity of Hcy not only to vascular endothelial cells (11, 12) but also to neuronal cells (10, 12, 13-16). Besides hyperhomocysteinemia, the deficiencies of folate and/or cobalamine will also limit the production of S-adenosyl- L-methionine (SAM), a methylation agent involved in the metabolic conversions, catalyzed by methyltransferases, of phosphatidylethanolamine, guanidinoacetate, norepinephrine and serotonin in phosphatidylcholine, creatine (and phosphocreatine), epinephrine and melatonin, respectively (9). When SAM loses its methyl group, it forms S-adenosylhomocysteine (SAH) (8, 9). Folate and/or cobalamine deficiencies are also associated with an increase in SAH, a potent inhibitor of methyltransferases (17) that will worsen the production of phosphatidylcholine, creatine (and phosphocreatine), epinephrine, and melatonin (8, 9). These factors are structurally or functionally determinants for the mood control. The lack of phosphatidylcholine in the neural cell membranes would be responsible for structural and functional degeneration. Since phosphocreatine is an energy source for immediate use not only in muscle but also in the brain, low phosphocreatine reserves would be the cause of muscle and brain asthenia generally present in depressed patients. Disequilibrium between norepinephrine and epinephrine would exacerbate the sympathetic responses, causing autonomous changes in the heart beats, a very common complaint in depressed individuals. A decrease in melatonin Received June 30, 2008 Accepted for publication September 10,

2 08 ALVES DE REZENDE/c:04 LORD_c 8/10/09 11:41 Page 618 production would be responsible for the sleeping disturbs usually associated to depression. Thus, selective deficiencies of folate and/or cobalamine are associated with depression and other neuropsychiatric disorders through determination of structural and functional deficits and degeneration in CNS (10, 14, 18, 19). These deficiencies have been shown to be implicated in the response to treatment of depressive disorders by fluoxetin (2). Regardless of the mechanism, depression is associated with selective deficiencies of folate and/or cobalamine without general malnutrition (20). On the other hand, the selective deficiencies of folate and/or cobalamine are also known causes of macrocytic anemia, which is related to increase in the Mean Corpuscular Volume (MCV) (21). These deficiencies impair erythropoiesis, causing immature precursors of erythrocytes to be released into the circulation (22). The degree of macrocytosis depends on the severity of the deficiencies; with milder deficiencies producing smaller increases in MCV, without characterize a macrocytosis condition. In this work, we focus on dualism, reporting the correlations we have observed between depression, based on the geriatric depression scale (GDS) scores (23), nutritional status, Mininutritional Assessment (MNA) scores (24-26), and selected haematologic variables, in the eligible institutionalized elderly patients who reside in the Brazilian city of Uberlândia. Subjects and methods Subjects This study had the approval of the Human Ethics Committee of the Federal University of Uberlândia and was duly authorized by each patient. The subjects were recruited from the residents of all six nursing homes existing in Uberlândia, a medium-size city in the Brazilian state of Minas Gerais, with approximately 600,000 residents. Uberlandia is comprised an elderly population of approximately 40,000 people, of which less than 200 are institutionalized in nursing homes. The patients that refused to participate, those under 60 years, and those living in a half-boarding system, were excluded. The subjects were classified by gender, age range (60-69, 70-79, and 80 or more years), and diagnosis of depression. Depression evaluation Depression was evaluated by the short version of the GDS (23), which consists of 15 subjective questions that have to be answered as yes or no by each patient. The summation of the points gives a total score ranging from 0 to 15. GDS scores of 6 or above are considered suggestive of depression (23). Nutritional assessment The evaluation of the nutritional status of each volunteer was performed with the MNA instrument (24-26), by one researcher, so as to avoid errors among observers in the MNA scores. The patients were classified as undernourished, at risk for undernutrition, and well-nourished when their total MNA scores (range of possible total scores, 0-30) were 17, DEPRESSION AND HAEMATOLOGIC VARIABLES , and 24, respectively. Haematologic evaluations Blood samples (5 ml) were collected by intravenous puncture in evacuated tubes containing 1 g.dl -1 EDTA, after overnight fasting (8-12 h). Erythrocyte count, haematocrit, and haemoglobin were assayed with a Coulter STKS Analyzer (Fullerton, CA, USA), and iron was analyzed with the Cobas Integra System (Indianapolis, IN, USA). Normal reference ranges for female and male subjects were and million per mm 3 (erythrocytes), 35-45% and 39-50% (haematocrit), and fl (MCV), and g.dl -1 (haemoglobin), and and μg.dl -1 (serum iron), respectively. Normal reference ranges for MCH (Mean Corpuscular Hemoglobin) and MCHC (Mean Corpuscular Hemoglobin Concentration) were pg and g.dl -1 for both genders. Statistical analysis All parameters examined (GDS, MNA, and hematologic variables) were subjected to descriptive statistical and correlation analyses, with help of the software package Origin 8.0 (Microcal, Northampton, MA, USA). Correlations were analyzed by the Spearman test, with p<0.05 indicating statistically significant dependencies. Results Table 1 shows the distributions of the institutionalized elderly subjects by gender, age range, and depression diagnosis. The population was comprised of 100 eligible individuals (61 females and 39 males), of which 60 (38 females and 22 males) were considered to have depression, as based on their GDS scores (GDS score 6). The percentage of patients with depression was larger in the year (71.9%) range than in the (43.3%) and the 80 year (63.2%) age ranges. Table 2 shows the mean values, variation, and reference ranges, and number and percentage of abnormal levels in GDS, MNA, and selected haematologic parameters obtained for the male and female institutionalized elders. The prevalence of depression (60% for the whole population) was higher among females (62.3%) than males (56.4%). The amount of undernourishment (MNA score 17) was higher among males than females, but abnormal levels of all hematologic parameters, except MCV, were higher in females than in males. Table 3 shows the parameters obtained in the correlation analyses between GDS scores and each of the other variables in the entire group and in each gender separately. Male GDS scores had significant negative correlations with the MNA scores, haematocrit, and haemoglobin. Female GDS scores did not have significant correlations with any of the variables, but a positive correlation with a p closer to the significance level (p < 0.05) was observed for MCV. Inclusion of all subjects in the analyses had a significant negative correlation for the MNA scores.

3 08 ALVES DE REZENDE/c:04 LORD_c 8/10/09 11:41 Page 619 Table 1 Distribution of elderly institutionalized individuals by age range and depression diagnosis Age range With depression Without depression Total (years) Female Male Both Female Male Both Female Male Both (23.3) 6 (20.0) 13 (43.3) 7 (23.3) 10 (33.3) 17 (56.7) 14 (46.7) 16 (53.3) 30 (100) (43.8) 9 (28.1) 23 (71.9) 6 (18.8) 3 (9.4) 9 (28.1) 20 (62.5) 12 (37.5) 32 (100) (44.7) 7 (18.4) 24 (63.2) 10 (26.3) 4 (10.5) 14 (36.8) 27 (71.1) 11 (28.9) 38 (100) Total 38 (38.0) 22 (22.0) 60 (60.0) 23 (23.0) 17 (17.0) 40 (40.0) 61 (61.0) 39 (39.0) 100 (100) Number in parentheses represents the percentage values in each age range Table 2 Mean values, variation and reference ranges, and abnormal levels and percentages in GDS, MNA, and hematologic parameters obtained for female (n=61) and male (n=39) institutionalized elders Variable Gender Mean ± SD Variation range Reference range Abnormal levels n % GDS scores Both 7.2 ± Female 7.3 ± Male 7.1 ± MNA scores Both 22.8 ± Female 22.7 ± Male 23.2 ± Haematocrit (%) Both 42.3 ± Female 41.0 ± Male 45.1 ± Haemoglobine (g.dl -1 ) Both 14.0 ± Female 13.4 ± Male 15.0 ± Iron (μg.dl -1 ) Both 70.1 ± Female 70.0 ± Male 86.1 ± MCV (fl) Both 91.0 ± Female 91.0 ± Male 91.4 ± Table 3 Correlation analyses of GDS with age, MNA, and some hematologic variables Variables Gender r n p Age Both Female Male MNA Both * Female Male * Erythrocytes Both Female Male Haematocrit Both Female Male * Haemoglobin Both Female Male * Iron Both Female Male MCH Both Female Male MCHC Both Female Male MCV Both Female Male Platelets Both Female Male * Statistically significant correlations (p<0.05). Discussion The prevalence of depression among the institutionalized elders from Uberlândia (60.0%) was greater than reported by Pouget et al. (27) (22.4%) and Torres et al. (28) (40.5%), using the same GDS-15 instrument with the same cut-off point (GDS score 6) in other institutionalized elders. The significant and negative dependence observed between the GDS and MNA scores for the conjunct of both genders and for the male subjects (Table 3) indicates that depression is inversely associated with the patient s nutritional status. This finding agrees with correlations already reported between depression and malnutrition (29). 619

4 08 ALVES DE REZENDE/c:04 LORD_c 8/10/09 11:41 Page 620 DEPRESSION AND HAEMATOLOGIC VARIABLES However, this observation could not be confirmed by the correlations between the GDS scores and the haematologic variables that are useful in evaluation of malnutrition, when the analyses considered the whole group of subjects or the female individuals separately (Table 3). However, significant and negative correlations were observed between the GDS scores and the haematocrit and haemoglobin levels in the male population (Table 3), in spite of the higher frequency of depression and haematologic abnormities among females (Table 2). These findings indicate that depression was directly associated with the degree of anemia in males, but not in females. The observed gender differences in the GDS dependences (Table 3) reflected a difference in the self-perception of the health state between genders, which may represent a true gender difference or may be just a consequence of the age differences among genders, since there was an increase in the percentage of females in the higher age ranges (Table 1). In fact, ageing can be a source of haematologic variability (26), such as the age-dependence reported for erythrocyte stability (30). Although female depression was not correlated with general nutritional status or the haematologic variables, the female GDS scores had a p value closer to the significance limit for the correlation with MCV. Since this trend represented a positive correlation with depression enhancing the increase in the MCV values, this suggests that female depression is associated with factors that are responsible for the increase in MCV. An increase in MCV is usually attributed to selective nutritional deficiencies of folate and/or cobalamine (21, 22), hydrosoluble vitamins that are metabolically related to brain structure and function. In fact, selective deficiencies of folate and/or cobalamine are associated with depression through determination of structural and functional deficits and degeneration in CNS (10, 14, 18, 19). The borderline positive correlation observed in this work between the GDS scores and the MCV values of the females probably resulted from folate and/or cobalamine deficiencies (21) that are associated with the ageing process (31). The existence of female patients with low levels of serum iron and haemoglobin (Table 2), which are known causes of microcytosis, produce antagonistic contributions in relation to the effects produced by folate and/or cobalamine deficiencies, which produce macrocytosis. If depression is associated with iron and haemoglobin deficiencies, we would expect to find negative correlations between the GDS scores and the MCV values. But if depression is associated with folate and cobalamine deficiencies, we would expect positive correlations between GDS and MCV (Table 3). The combination of some degree of microcytosis, caused by iron deficiency, with macrocytosis, caused by folate and/or cobalamine deficiencies, produce antagonistic effects on MCV. In fact, neuropsychiatric disorders are related to cobalamine deficiency in the absence of macrocytosis (32). Conclusions The severity of depression is related to the worsening of the nutritional status and the degree of anemia of the entire elderly population and of the elderly males. 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