Vitamin D efficacy on fall occurrence in elderly: a literature review

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1 Original article Ann Gérontol 2008 ; 1 (1) : e17-e25 Vitamin D efficacy on fall occurrence in elderly: a literature review GILLES BERRUT CHU hôpital Bellier, 41 rue Curie, Nantes Cedex <gilles.berrut@chu-nantes.fr> Reprints: G. Berrut Abstract. Vitamin D deficit and fall occurrence are frequent in elderly. Beyond the action of vitamin D on the risk of bone fracture, many studies analyzed the benefice of vitamin D supply on the fall risk. After research in the literature data base, 12 interventional randomized studies have been analyzed. Vitamin D supply reduces the fall risk by 40 to 60% in home-living or institutionalized elderly in 7 studies. The 5 negative studies reveal methodological difficulties such as the number of lost to follow-up, the frequency of vitamin D administration, the daily dose, the quality of data collection of falls. Vitamin D action can be explained by its muscular, cognitive or psychic action. A daily dose of at least 800 IU of vitamin D seems to be necessary in order to obtain a benefice. The reduction of the fall risk will be observed mainly in subjects initially having a level of 25(OH)D less than 75 nmol/l. Key words: elderly, fall, vitamin D, randomized study doi: /age V itamin D deficiencies are frequent in elderly [1, 2] living in institution [3] as well as those living in home [4]. These deficiencies are favored with age by the reduction in cutaneous synthesis capacity under the effect of sun rays (solar ultraviolet) [5], and the reduction in gastrointestinal sensitivity to vitamin D [6]. Vitamin D deficiency is a risk factor of bone fracture [7, 8]. Beside its action on bone remodeling, vitamin D acts directly on muscular activity by increasing flow [9] through specific receptor [10]. Fall is a frequent event in geriatrics at home as well as in institution. Its sequelae are major and often they lead to modifications in life style due to either direct consequence of fall or to change of residence place from home to institution. Many descriptive studies reported relationship between vitamin D and risk of fall in elderly. In a descriptive study [11], 83 old subjects (average 84 years) living in institution presented a mean level of vitamin D of 27 (18-37) nmol/l and a mean level of parathormone of 5.2 ( ) pmol/l. When we compare patients with history of fall (n = 33) to non-fallers (n = 50), vitamin D level is lower (22 vs. 29 nmol/l; p = 0.02) in the group of subjects with history of fall, and parathormone level is higher (6.2 vs 4.8 pmol/l; p < 0.01) in this group. A study of Flicker et al. [12] describes a population of old women (average 83.7 years) in which 667 women with weak dependency and 952 with high dependency. Vitamin D deficiency, defined by a concentration less than 25 nmol/l, is less frequent in low dependency group compared to high dependency group (144 (22%) vs 428 (45%)). After exclusion of women, which do not walk (n = 358), falls have been colligated during 5 months. Univariate analysis shows a relation between vitamin D and fall risk. Multivariate regression analysis after adjustment for factors having statistical relation with fall risk (weight, cognitive functions, psychotropes use, history of coll s fracture, and presence of behavior disorders) shows independent relation between vitamin D level and time of fall occurrence during follow-up period (RR: 0.74 [95% CI: ]; p = 0.01). We can resume this work by affirming that a vitamin D level multiplied by 2 is associated to a fall risk reduced to half. However, it is important to feature that it exists also an independent relation between fall risk and cognitive functions that are associated to gait disorders and to skill of walking outside. A wide cohort enrolled in the study of osteoporotic fractures has been analyzed, a posteriori, for fall risk by Faulkner [13]. Therefore, 9526 community-dwelling women, with median age of 70 years, have been followed-up during 4 years. All over population, there was not relationship between vitamin D level and fall risk. On the other hand women with a vitamin D level in the highest quartile had a significant reduction of falls (p = 0.039) in relation to those of lowest quartile. Vitamin D (D3) and intact PTH concentrations were not associated to risk fall, likewise muscular functional parameters (handgrip, chair-stand time, walking speed and reaction time). So that, vitamin D deficiency and fall risk are associated in old subjects. The effect of vitamin D supplementation on fall risk remains to be specified. Ann Gérontol, vol. 1, n 1, octobre 2008 e17

2 G. Berrut Methods Strategy of literature research We searched for all published articles in English and French languages in Medline base (Ovid, PubMed) from 1991 till june Keywords used in this research (Medical subjects Headings): randomized case-control study, randomized allocation, doubleblind and simple-blind method; vitamin D: cholecalciferol, calcitriol, or ergocalciferol; fall and human. Studies eligibility We have included all randomized double-blind studies whatever the used vitamin D form. We have differentiated studies that have the fall occurrence a main or secondary criterion, provided that the method of fall research is noted in the text. Only studies that define falls as change of position leading to stay on the ground were included. Falls had to be looked for by a systematic examination with relatively short search s intervals (less than 6 months). Subjects had to be clinically stable. Subjects age had to be over 60 years. The place of residence had to be specified and distinguished: home (community-dwelling included) and institutions whatever their specific definition which varies according to countries. Criteria of non-eligibility Non randomized studies were not retained. Studies containing imprecise data about falls or their methods of detection were excluded. Inclusion and exclusion criteria of subjects had to be specified in the text. Congress abstracts and letters for editor were not retained. Main outcome for analysis The main outcome measure was the occurrence of at least one fall by subject receiving vitamin D supplementation; whatever is the fall s expression, compared with those without vitamin D supplementation. Results Excluded studies The research has selected 48 articles. After exclusion according to mentioned criteria, 18 studies have been retained. Some of them have not been considered. The study of Sato [14] comparing alfacalcidiol to placebo during 3 months shows a benefit after vitamin D supplementation in term of number of fall per subject. But all subjects had Parkinson s disease and numerous fall factors in parkinsonian patients make results interpretation difficult. The study of Faulkner [13] includes 9,526 patients and compares subjects receiving vitamin D at least once per week with an equivalent dose of 400 IU per day (multivitamins intake included) to those with no supplementation. In this study, there is no randomization between groups. The double-blind randomized study of Burleigh [15] compares in 205 patients the association of 800 IU of vitamin D3 and 1,200 mg of to intake only. But this study is conducted in acute care setting and does not consider events occurring during hospitalization. Finally, the study of Latham [16] compares the intake of single dose of 300,000 IU calciferol to placebo after randomization. The enrolled 243 subjects are hospitalized in acute care setting and the follow-up is done in the following 6 months. We considered that in this study patients are not clinically stable and diseases motivating hospital admission might severely interfere with fall occurrence. Dawson-Hughes et al. [17] report a double-blind randomized intention-to-treat analysis, comparing 700 IU of cholecalciferol associated to 500 mg of citrate to placebo for each. The main study criterion is the occurrence of non vertebral fractures. Falls are recorded by means of postal cards sent by subjects after fall occurrence, followed by a phone call by investigators. All over 3 years, 445 ambulatory subjects (71 ± 5 years) are followed-up, but results about falls, qualified as non significant are not reported in the text. Finally, the study of Triverdi [18] does not mention the randomization method and does not clearly determine the definition and the recording method of fall occurrence during the follow-up. Included studies Twelve studies fulfill the analysis conditions (tables 1 and 2). In 2000, Pfeifer et al. [19] compare randomly and in double-blind, the intake of 800 IU vitamin D3 associated with 1,200 mg of to intake only, in 148 home-dwelling subjects (74.8 ± 0.5 years). At inclusion, subjects had to have 25(OH)D concentrations less than 50 nmol/l. The initial observed concentration is ± nmol/l. The main outcome of the 1-year e18 Ann Gérontol, vol. 1, n 1, octobre 2008

3 Ann Gérontol, vol. 1, n 1, octobre 2008 e19 Table 1. Method of studies about contribution of vitamin D for the risk of fall. Authors Study method Intervention Controls n Follow-up period Chapuy, 2002 [21] Bischoff, 2001 [22] Bischoff, 2006 [23] Bischoff, 2006 [24] Law, 2006 [25] Pfeifer, 2000 [19] Broe, 2007 [26] Gallagher 2001 [20] Dukas, 2004 [27] Porthouse, 2005 [28] Prince, 2008 [29] Pfeifer, 2007 [30] R, DB, ITT 800 IU D3 + 1,200 mg R, DB, ITT 800 IU D3 + 1,200 mg R, DB 800 IU D3 + 1,200 mg R, DB 700 IU D mg maleate R, treatment allocation by care unit R,DB, 25(OH)D < 50 nmol/l at inclusion 2,5 mg/day each 3 months (equivalent to 1,100 IU per day) 800 IU D3 + 1,200 mg R, DB 4 arms: 200, 400, 600 et 800 D2 R 3 arms: HST; HST + vitamin D; vitamin D R, DB alphacalcidiol 1 μg/day R, opened, at inclusion presence fragility factor R, DB, inclusion 25(OH)D < 25 ng/ml R, inclusion 25(OH)D < 78 < nmol/l R: randomized; DB: double blind; ITT: intention-to-treat 800 IU D3 + 1,000 mg + advices 1,000 IU ergocalciferol + 1,000 mg 800 IU D3 + 1,000 mg Mean age (years) Place of residence Placebo years 84,9 Residential center 1,200 mg 1,200 mg Main outcome Fall Analysis of falls No information about methods of data collection months 85 Institution Fall Daily assessment by a nurse 64 4 months Institution Balance performance Daily assessment by a nurse Placebo years 71 Home Fall Systemic phone call + information posted by subjects, then follow-up visit Placebo 3, years 85 Institution Fracture Record of events occurring in care unit, completed by caregivers 1,200 mg 4 arms: 200, 400, 600 and 800 D year 74.8 Home Secondary hyperparathyroidism Questionnaires sent to subjects months 89 Institution Fall Computerized form of events occurring in care unit, completed by caregivers Placebo months 72 Home Bone loss Interview every 6 months Placebo months 75 Home Fall Regular interview (frequency not indicated) Advices 3, months > 70 Home Fracture Self notification of falls during first 6 months 1,000 mg 1,000 mg year 73 Home Fall Interview every 6 weeks months 77 Home Fall Record of falls completed by the subject Vitamin D and fall

4 G. Berrut Table 2. Results of studies about contribution of vitamin D for the risk of fall. Authors Initial vitamin D concentration Relative risk of fall Frequency of falls by group (%) Chapuy, 2002 [21] μg/l (a) NR 63.9 vs 62.1 (NS) Bischoff, 2001 [22] 12.3 ( ) ng/ml (b) 0.68 [ ] 22.6 vs 30 (NS) Bischoff, 2006 [23] ng/ml 0.40 [ ] 18 vs 67.7* Bischoff, 2006 [24] ng/ml Women: 0.54 [ ] Men: 0.93 [ ] Law, 2006 [25] 47 (35-102) nmol/l 1.09 [ ] 44 vs 43 (NS) Pfeifer, 2000 [19] nmol/l 16 vs 28* Broe, 2007 [26] 19.5 ng/ml 0.20 [ ] 200 IU: 58%; 400: 60%; 600: 60%; 800: 20%*; placebo: 44% Gallagher, 2001 [20] nmol/l NR HST: 56%; HST vit. D: 56; vit. D: 48%; Placebo: 63% Dukas, 2004 [27] pg/ml 0.69 [ ] If dietary intake > 512 mg/day: 0.46 [ ]* and if < 512 mg/day: 1.09 [ ] Porthouse, 2005 [28] NR 0.99 [ ] Prince, 2008 [29] ng/ml 0.61 [ ]* Pfeifer, 2007 [30] nmol/l 0.61 [ ]* a) mean + standard deviation; b) median (extreme values). RR [95% CI]. * p < 0.05; NR: not reported. Other results concerning risk of fall 28.0 vs 31.2* Post hoc subgroup of non active women 0.35 [ ] Comparison of subjects receiving vitamin D with all others: reduction of falls frequency (p = ) follow-up was the effect of the treatment on the parathyroid function, in spite of this, falls have been gathered by means of a systematic questionnaire. The vitamino-calcic supply is associated with a reduction in the number of faller subjects (16 vs 28%; p = 0.037). Gallagher [20] realizes a randomized 4-arm trial (Hormone Substitution Treatment (HST)/HST + calcitriol/ calcitriol/placebo) in 489 home-dwelling menopaused women (72 ± 3 years). The main outcome is bone loss on osteodensitometry, but falls are systematically searched for by means of a 6-week interview during a period of 3-year follow-up. The initial 25(OH)D concentration is 80.5 ± 27.4 nmol/l. The number of faller subjects is comparable in the 4 arms. On the other hand, the analysis of subjects receiving calcitriol shows a reduction in falls (p = ). Falls results by group are not reported. The comparison of 800 IU of vitamin D3 associated with 1,200 mg of to placebo is reported by Chapuy [21] in a large cohort of 610 homedwelling women (84.9 ± 6.6 years). The main outcome of the 2-year follow-up is fall occurrence, but the method used to gather events is not precisely reported. The initial 25(OH)D concentration is 8.5 ± 5.3 μg/l. There is no reduction in the number of fall while the number of hip fracture decreases (OR: 1.69 [95% CI: ]). Bischoff, in a first work [22] compares 800 IU of vitamin D3 and 1,200 mg of to 1,200 mg of only in a randomized double-blind intentionto-treat study, in 122 institutionalized subjects (85 ± 6 years). The fall is the main outcome, recorded daily by nurses in institutions. The initial 25(OH)D concentration is 12.3 [extreme values: ] nmol/l. After a 3-year follow-up, the number of faller subjects is comparable in the 2 groups (14/62 vs 18/60; RR: 0.68 [95% CI: ]). Muscular performances are improved in the group treated for knee extensor and flexor strength and grip strength (p = ). However, 30% of the initial sample size is lost to follow-up. In 2006, the team of Bischoff reports 2 studies. The first [23] includes 64 patients living in institution and aged 65 to 97 years. The same treatment is compared (800 IU vitamin D + 1,200 mg vs 1,200 mg ) after randomization and doubleblind administration. The follow-up is over 3 years according to the same modalities. The initial vitamin D concentration is 16.4 ± 9.9 ng/ml. The treated group develops less falls than the placebo group 6/33 vs 21/31; 0.40 [ ]). The second study [24] enrolls e20 Ann Gérontol, vol. 1, n 1, octobre 2008

5 Vitamin D and fall 445 home-dwelling subjects (71 ± 5 years) receiving either 700 IU of vitamin D3 and 500 mg of, or a placebo. The initial 25(OH)D concentration is 26.6 ± 12.7 ng/ml. After 3-year follow-up (card sent by the subject after a fall, at home interview, phone call), it is noted a reduction in the number of falls in women (0.54 [ ]) and not in men [0.93 [ ]). The benefit is more marked in less active women (0.35 [ ]). A large cohort of 3,717 subjects (mean age: 85 years) is included by Law [25] for comparison (randomized, double-blind) between 2.5 g ergocalciferol every 3 months (equivalent to 1,100 IU per day) and placebo. Institutionalized subjects are followed-up during 10 months with a systematic events collection (fracture and fall) by nurses in institutions. The initial 25(OH)D concentration is 59 [35-102] nmpl/l. There is no positive impact on falls (777/2,917 vs 833/3,728; 1.09 [ ]) or on the frequency of fractures. In order to determine the necessary dose of vitamin D, Broe [26] conducts a 5-arm randomized trial (200, 400, 600, 800 IU and placebo) in 124 subjects (89 ± 5 years) living in institution. The fall occurrence is the main outcome systematically gathered. The initial 25(OH)D concentration is 19 ng/ml. After 5 months, only the subjects receiving 800 IU of vitamin D3 have a reduction in the number of falls (58, 60, 60, 20, 44% respectively). The comparison between subjects receiving 800 IU and others shows a 72% reduction in the number of fallers (0.20 [ ]). The alfacacidiol (1 μg per day) is compared to placebo, by Dukas [27], in 378 home-dwelling subjects (75.0 ± 4.0 years). The initial 25(OH)D is 39.1 ± 10.9 pg/ ml. After a 9-month follow-up with systematic interviews about falls, a non-significant reduction in fallers number is observed in the treated group (0.69 [ ]). A post-hoc analysis assessing the level of supply shows that only patients who received more than 512 mg of per day had a significant reduction in the number of fall (0.46 [ ]). Porthouse [28], in a large randomized opened trial including 3,314 home-dwelling subjects aged over 75 years, compares 800 IU of vitamin D3 and 1,000 mg of to nutrition advices. After 2-year follow-up, falls collected by self-modification are not less frequent in the treated group (0.99 [ ]). In this study, the frequency of fractures, which was the main outcome is not reduced and there is no change in the quality of life. The study of Prince et al. [29] reports the comparison of 1,000 IU of ergocalciferol and 1,000 mg of to supply only (randomization, doubleblind), in 302 subjects (77.0 ± 4.2 years) living at home and having an initial level of 25(OH)D less than 24 ng/ml as an inclusion criterion. The fall, which is the main outcome is collected by means of a 6-week systematic interview. We observe a reduction in the number of falls (0.61 [ ]) by 40%. Recently, Pfeifer [30] makes the comparison between 800 IU of vitamin D3 associated with 1,000 mg of and a group treated only by, in 242 home-dwelling subjects having an initial 25(OH)D less than 78 nmpl/l. The main outcome is fall occurrence collected on a record. After 20-month follow-up, we also observe 40% reduction in the number of fallers (0.61 [ ]). In this study it is also reported a decrease in the time needed to perform the timed get up and go test as well as an improvement in the quadriceps strength. Discussion Vitamin D, placebo and Out of the 12 studies randomly comparing the effect of vitamin D supply to placebo or to only, 7 show a reduction in the fall risk [19, 23, 24, 26, 27, 29, 30]. The fall risk reduction varies from 40 to 60% in these studies, whatever the comparison is with placebo or supply, in institution or at home. The analysis of the 5 articles [20-22, 25, 28] not showing an efficacy of vitamin D supplementation highlights weaknesses in some methodological aspects of these studies: the initial concentration of vitamin D [20, 25], the type of vitamin and its dose [26], the frequency and mode of drug administration [16, 25], the mode of follow-up and fall occurrence [21, 28], the importance of lost to follow-up [22]. The initial level of vitamin D was often reported as an explanation for the negativity of the studies; this is why the inclusion criteria of more recent trials define a sufficient initial low vitamin D concentration. For example, in the study of Pfeifer [30] the initial level of vitamin D was less than 78 nmol/l. However, when we take in consideration vitamin D mean values, we observe no significant difference between positive and negative studies. The mean vitamin D level of all studies is of 48.7 nmol/l: 33 nmol/l for negative studies, and 54.6 nmol/l for positive ones. On the other hand, the ratio of standard deviation to mean values shows a variability coefficient about 60% in the negative study of Chapuy [21], while recent studies [29, 30] which exclude low values, have a variability coefficient of Ann Gérontol, vol. 1, n 1, octobre 2008 e21

6 G. Berrut 30%. This highly influences the number of subjects needed to be included and may participate in the negative results. Vitamins D2 and D3 Many authors have reported differences of efficacy between vitamins D2 (ergocalciferol) and D3 (cholecalciferol). In our analysis, this difference seems to be not so distinct. Four studies [19, 23, 24, 30] using the vitamin D3 are positive and 3 are negative [21, 22, 28]. For the ergocalciferol, 2 studies are positive [26, 29] and one is negative [25]. Dukas [27] is the only to use alfacalcidiol in his study with positive result. Some studies assessed the efficacy of vitamins D2 and D3 on the increase of 25-hydroxyvitamin D level. The vitamin D2 seems to be three time less effective than vitamin D3 [31, 32]. Harris et al. observed that vitamin D2 is less effective with age [33, 34]. However, other studies show that vitamin D2 is quite effective [35-37]. A recent study [31] comparing the respective efficacy of vitamins D2 and D3 shows that both vitamins lead to a comparable rise in the level of 25(OH)D after 3 days, but the level diminishes more rapidly with vitamin D2. This study highlights the importance to respect certain delay between administrations according to the type of vitamin D used. This could explain the negative result of Law s study [25] in which ergocalciferol every 3 months. Several authors pointed out the importance of daily dosages on the contrary of 3 or 6-month dosages that have a less or even negative effect. Hypotheses about lack of efficacy feature in the old subject a difficulty to maintain stores on the contrary of the adult subject. A study comparing intramuscular, intravenous and oral administrations of vitamin D, shows a slower raise of 25(OH)D levels with intramuscularly injected vitamin D. This animal model study in rats shows that half of the intramuscularly injected vitamin D, is destructed in situ [38]. Importance of the dosages of vitamin D The study of Broe [26] undermines the importance of the dosages because only those of 800 IU are superior to placebo and not those of 200, 400 and 600 IU. In a meta-analysis concerning the relationship between vitamin D and risk of hip fracture, the benefice is only observed at a daily dosages superior to 700 IU [39]. Size of studies We can note that studies with a large sample size have negative results [25, 28]. This is probably due to difficulties to ensure an exclusive follow-up of falls; on the contrary, the trained team-works with smaller sample size have more frequently positive results whether in institution [23] or in home [24]. The follow-up in institution is based on records of events or a formulary completed by caregivers. On the other hand, in case of home-living subjects the auto-notifications are not adapted because elderly people are often reluctant to admit the fall, considering it as a sign of loss of autonomy. Questionnaires and systematic interviews with sufficiently short delays seem to be adapted. Postal card sent to the investigation center after fall occurrence should be followed by an interview in order to assert the fall event. Longitudinal studies in elderly are confronted to problems of lost to follow-up. HA Bischoff-Ferrari puts forward this argument since in his study 30% of patients could not be followed-up. Similarly, Lyon [40] notes that the number of lost to follow-up is a part of major difficulties in conducting studies in elderly subjects, especially on the occasion of fall occurrence, since it is an event leading to a change in the place of residence. Some factors may influence results Other non-considered factors may influence results of these studies such as risk-taking, parathyroid myopathy or genetic factors. The increase of fracture risk at the time of vitamin D supplementation should evoke, beside a lack of luck or a recruitment bias, a side effect due to the improved muscular function. At the time of gait rehabilitation, it is common to notice that the confidence gain in walking is responsible for increasing in risk-taking and therefore in the frequency of falls. In the same manner, we can suspect with Smith et al. [41] that muscular function improvement under the effect of vitamin supplementation leads to increasing physical activity. Because of the delayed gain in the bone mass, this activity will lead to more risks of fall and fracture. The raised parathormone level due to vitamin D deficiency may result in a myopathy. In the study of Stein, cited before, the multiple regression analysis has shown that only parathormone has been independently associated with fall risk [11]. As it has been noted with parathyrodectomies for hyperparathyroidism, 6 to 12 months are needed between PTH levels normalization and the parathyroid myopathy disappearance. Polymorphisms of the gene coding for vitamin D receptor can also intervene; in the study of Onder et e22 Ann Gérontol, vol. 1, n 1, octobre 2008

7 Vitamin D and fall al. [42], the genotype BB of bsml polymorphism is associated with a higher fall risk (19.5% of subjects) than the genotype bb (5.9%). So, the genotype bb protects against falling (RR: 0.14 [95% CI: ]). In this study, the polymorphism fokl of the same gene has no influence on fall risk. How can vitamin D reduce the fall risk? The relationship between vitamin D and reduction of fall risk can involve many mechanisms of which a functional action on balance, muscle, cognitive functions and psyche. Balance In a post hoc analysis of Bischoff-Ferrari study [23], gait and balance performances in 64 elderly institutionalized women (65-97 years) have been assessed by means of an electronic device system recording the degree of trunk angular displacement and angular velocity during standing position eyes open and during changing of positions from sitting down to standing up. In this population, vitamin D supplementation reduces the risk of fall (RR: 0.40 [95% CI: ]). After the adjustment of the regression analysis results on the metrological parameters of posture, it was found that trunk angular displacement significantly influences the relationship between vitamin D and fall (22%) and after the adjustment for the dynamic parameters it was noted that angular velocity had the most influence on the result (14%). Similarly, Pfeifer et al. [30] observes that vitamin D supplementation improves the time needed to perform the timed get up and go test and increases the quadriceps strength, which means a direct action on the muscular function. Muscle Since the first descriptions of muscular weakness in rickets and ostomalacia, the importance of vitamin D for muscular function has been recognized [41, 43-45]. High serum levels of vitamin D are associated with a better muscular function and can explain the positive effect of vitamin D on fall in elderly subjects [46, 47]. For example, it was reported an improvement in the grip strength and the chair-stand [48] or in knee extensor strength [49]. C Anweiller et al. [50] confirm the relationship between a low level of vitamin D and the diminution in the grip strength, but they indicate the confounding factors altering the independency of this relation: age, basal metabolic index, physical training and number of co-morbidity. Nevertheless the fact remains that the vitamin D supplementation constantly shows an improvement in muscular performances in case of vitamin D deficiency with clinical expression of osteomalacia (25(OH)D < 7 nmol/l) [51] or in cases of defect in vitamin D (< 20 nmol/l) [52, 53]. Cognitive functions The relationship between vitamin D and cognitive functions deterioration has been investigated in preliminary works. A retrospective work including older adults consulting for memory problems [54] reports a statistical correlation between MMS score and serum vitamin D concentration. In a cohort of 225 patients with Alzheimer disease [55], the 25(OH)D3 concentration is associated with MMS score whereas there is no relation with vitamin B1, B6 and B12. Also, a transversal study [56] compares demented subjects (n = 20) to non demented controls (n = 40). Whereas, there is no difference in bone mineral density between both groups, the 25(OH)D is lower (61 ± 33 vs 90 ± 38 nmol/l; p < 0.01), and the PTH is higher (4.9 ± 2.1 vs 2.9 ± 1.7 pmol/l; p < 0.01) in demented patients. However, these transversal studies do not exclude the possibility of an indirect relation between cognitive deteriorations and a reduction in sun exposure secondary to gait disorders or dietary modification. Depression The relationship between depression and vitamin D deficiency has been investigated in 1,282 subjects, aged 65 to 95 years, from the Longitudinal Aging Study Amsterdam cohort [57]. The 25(OH)D concentration was diminished by 14% in the 169 subjects presenting minor depression, and by also 14% in the 26 subjects with an episode of major depression (p < 0.001). The PTH level was higher by 5 and 33% respectively (p < 0.003). A transversal study [58] including 80 patients (40 Alzheimer and 40 non demented controls) shows a relationship between vitamin D deficiency and a depressive episode (OR: [ ]; p =0.022). In practice All these possible actions on balance, strength, muscular performances, cognitive functions or mood Ann Gérontol, vol. 1, n 1, octobre 2008 e23

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