Sunteți pe pagina 1din 8

Treatment of dementia

http://www.uptodate.com/contents/treatment-of-dementia?view=print

Official reprint from UpToDate www.uptodate.com 2011 UpToDate

Treatment of dementia
Authors Daniel Press, MD Michael Alexander, MD Disclosures Last literature review version 19.3: Setembro 2011 | This topic last updated: Outubro 17, 2011 INTRODUCTION Advances in the understanding of the pathophysiology of dementing illnesses has changed the management of patients with these disorders from a conservative, symptomatic approach to a more biologically and medically specific one. The mainstay of management is still symptomatic: treatment of behavioral disturbances, environmental manipulations to support function, and counseling with respect to safety issues. The future promises disease-specific and, hopefully, disease-modifying treatments. The first step in management is an accurate diagnosis of the type of dementia. (See "Evaluation of cognitive impairment and dementia".) In the past, a rudimentary, and nearly always negative, work-up was conducted to rule out a "reversible" cause of dementia, leaving "senile dementia" as a default diagnosis. When no diseasespecific treatments were available, that approach had a certain logic, but it is no longer adequate. A more precise diagnosis is required for effective management and accurate prognosis. As an example, a practitioner who misdiagnoses "senile dementia" in a patient with progressive memory problems and visual hallucinations, overlooking very mild parkinsonism, might initiate treatment of hallucinations with haloperidol. This apparently sensible symptomatic treatment exposes the patient, who most likely has dementia with Lewy bodies (DLB), to severe and even life-threatening deterioration [1]. Addressing the treatment behavioral problems is an important aspect of the care of patients with dementia. This topic is discussed separately. (See "Treatment of behavioral symptoms related to dementia".) The management of medical problems can be more complex in patients with dementia [2]. Patients with dementia have a decreased ability to make decisions, to adhere to treatment plans (including medication compliance), and to report adverse effects of therapy [3,4]. A close discussion with the patient's caregiver is essential in mitigating these factors. Finally, patients with advanced stages of dementia appear to have diminished survival when faced with acute illnesses [5]. Available options for therapy and the outlook for new options, based upon our understanding of the pathophysiology of dementia, are discussed here. Safety and societal issues in patients with dementia are discussed separately. (See "Safety and societal issues related to dementia".) Efforts at prevention of Alzheimer disease (AD) and vascular dementia (VaD) are discussed separately. (See "Prevention of dementia" and "Risk factors for dementia" and "Mild cognitive impairment: Epidemiology, pathology, and clinical assessment".) CHOLINESTERASE INHIBITORS Patients with Alzheimer disease (AD) have reduced cerebral production of choline acetyl transferase, which leads to a decrease in acetylcholine synthesis and impaired cortical cholinergic function. Cholinesterase inhibitors increase cholinergic transmission by inhibiting cholinesterase at the synaptic cleft. Four cholinesterase inhibitors, tacrine, donepezil, Section Editors Steven T DeKosky, MD, FAAN Kenneth E Schmader, MD Deputy Editor Janet L Wilterdink, MD

1 de 8

05-12-2011 22:21

Treatment of dementia

http://www.uptodate.com/contents/treatment-of-dementia?view=print

rivastigmine, and galantamine are currently approved for use in AD by the US Food and Drug Administration (FDA). These are discussed in more detail separately. (See "Cholinesterase inhibitors in the treatment of dementia".) MEMANTINE Memantine (Namenda; Axura in Europe) is an N-methyl-D-aspartate (NMDA) receptor antagonist. The mechanism of action of memantine is distinct from that of the cholinergic agents; it appears to be neuroprotective. Glutamate is the principal excitatory amino acid neurotransmitter in cortical and hippocampal neurons [6]. One of the receptors activated by glutamate is the NMDA receptor, which is involved in learning and memory [7]. Excessive NMDA stimulation can be induced by ischemia and lead to excitotoxicity, suggesting that agents that block pathologic stimulation of NMDA receptors may protect against further damage in patients with vascular dementia (VaD) [8]. In addition, the physiologic function of the remaining neurons could be restored, resulting in symptomatic improvement [9]. Memantine has been available internationally and was approved by the US Food and Drug Administration (FDA) in October 2003 for use in patients with moderate to severe AD. Memantine appears to be effective in patients with moderate to severe AD. A 28-week randomized trial in 252 patients with Mini Mental Status Examination (MMSE) scores of 3 to 14 (mean approximately 8) at study entry found that memantine significantly reduced deterioration on multiple scales of clinical efficacy [10]. Adverse event rates with memantine were similar to placebo, and more patients taking placebo than memantine discontinued the study medication. An open label extension to this study demonstrated benefits for patients previously taking placebo in all efficacy measures relative to their previous rate of decline, and also confirmed the favorable adverse event profile seen in the double blind study [11]. There is little, if any, evidence that patients with milder disease benefit from memantine. A systematic review reported the results of pooled data from three unpublished studies of memantine in mild to moderate AD [12]. Intention to treat analysis indicated a very small but statistically significant beneficial effect for memantine at six months on cognition (<1 point on the 70-point ADAS-Cog) but no effect on behavior or activities of daily living. Another study analyzed data on 431 patients with mild AD (MMSE 20 to 23) from three trials and found no substantial benefit with memantine [13]. Memantine also has some efficacy in patients with VaD. (See "Treatment and prevention of vascular dementia".) Memantine also appears to have fewer side effects than the cholinergic agents [12]. Dizziness is the most common side effect associated with memantine. Confusion and hallucinations are reported to occur at a low frequency, but we have noticed that memantine use seems to increase agitation and delusional behaviors in some patients with AD. Others have reported that worsening of delusions and hallucinations is particularly problematic in patients who have dementia with Lewy bodies (DLB) [14]. A number of questions about memantine remain to be answered: Will long-term treatment benefit those with mild to moderate AD? Is it truly neuroprotective? Will additional toxicities appear when it is used in larger numbers of people? In spite of these unanswered questions, the data look promising and alternative treatments, especially for those with advanced disease, are few. A 2008 systemic review concluded that memantine has been shown to improve cognition and global assessment of dementia, but with small effects that are not of clear clinical significance; improvement in quality of life and other domains are suggested but not proven [15]. As a result, treatment decisions should be individualized and include considerations of drug tolerability and cost [16]. Memantine plus cholinesterase inhibitors Memantine may also be beneficial when used in combination with cholinesterase inhibitors:

2 de 8

05-12-2011 22:21

Treatment of dementia

http://www.uptodate.com/contents/treatment-of-dementia?view=print

A 24-week trial studied the effects of either memantine or placebo in addition to donepezil in 322 patients with moderate to severe AD [17]. MMSE scores ranged from 5 to 14 (mean approximately 10) at study entry. Treatment with memantine plus donepezil resulted in significantly better outcomes than placebo plus donepezil on measures of cognition, activities of daily living (ADLs), global outcome, and behavior. Significantly more patients taking placebo than memantine discontinued the trial, and the rate of discontinuation due to adverse events was lower in the memantine-treated group than the placebo group. A second 24-week randomized trial compared memantine to placebo in 433 patients with mild to moderate AD who were on stable doses of a cholinesterase inhibitor (either donepezil, rivastigmine, or galantamine) [18]. There was no difference in outcome measures between the treatment groups. We use memantine in combination with a cholinesterase inhibitor in patients with advanced disease. Since it may be disease-modifying, we continue memantine even when there is no clinical improvement. OTHER MEDICATIONS Vitamin E and selegiline Alpha-tocopherol (vitamin E) and selegiline (a monoamine oxidase inhibitor) have been studied in AD because of their antioxidant properties. The largest and most influential, but controversial, trial examining disease progression in AD was the first Alzheimer's Disease Cooperative Study (ADCS) that compared selegiline, alpha-tocopherol, or both with placebo [19]. The primary outcome in the study was time to a combined endpoint of death, institutionalization, loss of the ability to perform ADLs, or progression to severe dementia on a Clinical Dementia Rating scale. There was a delayed progression to outcome in the ADCS treatment groups (placebo 440 days, selegiline 655 days, alpha-tocopherol 670 days, combined treatment 585 days) [19], but their analysis required statistical adjustment because the placebo group had higher MMSE scores at baseline. A number of cognitive tests that were measured as secondary endpoints (including the MMSE and the Alzheimer Disease Assessment Scale, cognitive subscale) failed to show any difference between the groups. A number of other smaller studies have also investigated the use of selegiline with varying results. A meta-analysis of 12 trials, including the one just discussed, found that eight of the studies suggested some beneficial effect of selegiline in the treatment of cognitive benefits and, in three trials, in the treatment of behavior and mood [20]. Three studies that were longer than one year reported significant delays in time to the primary outcome (death, institutionalization, loss of ability to perform ADLs, or severe dementia) [19,21,22]. However, the magnitude of the benefits in the meta-analysis was small and largely dependent on one study [19]. Thus, the clinical importance for the population at large is unclear. In spite of these caveats, these are the first studies to demonstrate a delay to a significant clinical endpoint in AD. Since alpha-tocopherol and selegiline did not differ in terms of efficacy in the largest study, and their combination was no better than either agent alone (and in fact was non-significantly worse), we generally suggest that patients with AD take alpha-tocopherol at a dose of 1000 IU twice daily. We see no advantage for the use of selegiline, which has more side effects and is more costly. A practice parameter from the American Academy of Neurology stated that vitamin E likely delays the time to clinical worsening [23]. There is growing concern regarding the risk of mortality associated with vitamin E supplementation (see "Vitamin supplementation in disease prevention"), and such supplementation is appropriate only for patients with AD or at high risk of developing AD (ie, those who have more than one family member with AD) who lack significant heart disease. We do not recommend vitamin E for the routine prevention of AD or other types of dementia. Estrogen replacement Studies of estrogen and AD in postmenopausal women have focused on

3 de 8

05-12-2011 22:21

Treatment of dementia

http://www.uptodate.com/contents/treatment-of-dementia?view=print

two areas: the role of estrogen in preventing the development of dementia; and the potential efficacy of estrogen in the treatment of dementia. These investigations are based upon a large body of preclinical evidence that estrogen enhances cerebral blood flow, prevents atrophy of cholinergic neurons, reduces oxidative stress, and modulates the effects of nerve growth factors [24]. However, large randomized trials have now shown that the use of hormone replacement therapy (HRT) with estrogen plus progestin or estrogen alone in women aged 65 and older who are free from dementia may increase the risk of developing dementia [25-27]. (See "Estrogen and cognitive function", section on 'Estrogen and dementia'.) Until recently, the majority of studies of estrogen therapy for the treatment of AD have been uncontrolled, unblinded, and of short duration [28]. Three randomized controlled trials of estrogen therapy for treatment of AD involving 42, 50, and 120 women had similar results: treatment with estrogen at varying doses and for a varying duration of time did not improve cognitive or functional outcomes compared with placebo [29-31]. A fourth trial reported different results: in 20 postmenopausal women with AD who were treated with a relatively high dose of 17 beta estradiol by skin patch (0.1 mg/day) or placebo, active treatment was associated with significant improvement in verbal memory, visual memory, and attention [32]. A meta-analysis found that women who had menopause symptoms had improvements in verbal memory, vigilance, reasoning, and motor speed with estrogen replacement, but no enhancement of other cognitive functions [33]. No benefits were observed in asymptomatic women. (See "Estrogen and cognitive function".) Estrogen does not appear to enhance the effects of cholinesterase inhibitors in patients with AD. A study of 117 women that looked at adding hormone replacement therapy (transdermal estradiol and oral progesterone) to treatment with rivastigmine found no additional benefit in the women randomized to receive hormone replacement therapy [34]. In summary, we see no current evidence for initiating ERT in patients with established dementia, and, given the data on HRT for primary prevention of dementia, ERT may actually be harmful. (See "Estrogen and cognitive function".) Antiinflammatory drugs A role for the use of antiinflammatory drugs in the treatment and prevention of AD continues to be investigated. Pathophysiological studies have demonstrated an amyloid-induced inflammatory reaction with microglial activation and cytokine release [35,36]. In addition, some epidemiologic studies have suggested that use of nonsteroidal antiinflammatory drugs (NSAIDs and other antiinflammatory medications) are associated with a reduced odds-ratio for developing AD [37,38]. (See "Prevention of dementia", section on 'NSAID therapy'.) However, clinical trials do not support this treatment: Except for one small clinical trial of indomethacin [39], randomized trials of antiinflammatory medications including, naproxen, hydroxychloroquine, diclofenac, rofecoxib, and aspirin have not found a benefit for these agents in slowing cognitive decline in patients with AD [40-44]. In addition, adverse events have been more common in treated patients compared with controls. In particular, long-term use of the COX-2 inhibitor rofecoxib has been associated with an increased risk of cardiovascular events, and this problem may be a drug class effect of COX-2 inhibitors. In addition, a placebo-controlled AD prevention trial comparing celecoxib to naproxen was suspended in December 2004; the suspension was due to the finding of an increased rate of cardiovascular events in patients receiving celecoxib in an unrelated colonic polyp prevention trial; however, it was announced that subjects receiving naproxen sodium had an increased rate of cardiovascular events. These issues are discussed in detail elsewhere. (See "COX-2 selective inhibitors: Adverse cardiovascular effects" and "Nonselective NSAIDs: Adverse cardiovascular effects".) Ginkgo biloba A systematic review of ginkgo for cognitive impairment and dementia concluded that ginkgo biloba, while safe, has inconsistent and unconvincing evidence of benefit [45]. We do not advocate use of ginkgo because of questionable efficacy and lack of regulation, including variability in the dosing and contents of herbal extracts [46]. The studies evaluating ginkgo biloba

4 de 8

05-12-2011 22:21

Treatment of dementia

http://www.uptodate.com/contents/treatment-of-dementia?view=print

for the prevention and treatment of dementia are presented elsewhere. (See "Clinical use of ginkgo biloba", section on 'Treatment of dementia' and "Prevention of dementia", section on 'Ginkgo biloba'.) Statins While there have been investigations in a potential role of statin therapy in the prevention and treatment of Alzheimer disease, there is as yet, no established role for statins for these indications. (See "Prevention of dementia", section on 'Statins'.) A pilot clinical trial demonstrated trends toward benefit for atorvastatin in a 63-patient trial of mild to moderate AD [47]. However, a randomized controlled trial of simvastatin (40mg per day for 18 months) in 406 patients with mild to moderate AD found no evidence of benefit of therapy on the progression of AD symptoms [48]. Dietary supplements Vitamin B Supplementation with B vitamins, in particular those that are involved in homocysteine metabolism, have been studied in patients with AD in hopes that they may demonstrate efficacy in preventing or slowing the progression of AD. An 18-month randomized trial of high dose vitamin B-complex supplementation (folate, B6, B12) in 340 patients with mild to moderate AD found no beneficial effect on cognitive measures [49]. A discussion of the rationale and clinical utility of vitamin B-complex supplementation in the prevention of AD is discussed separately. (See "Prevention of dementia", section on 'Vitamins B6, B12, and folate'.) Omega-3 fatty acids Observational studies have suggested a possible association between dietary intake of fish and omega-3 fatty acids and a lower risk of dementia. (See "Prevention of dementia" and "Prevention of dementia", section on 'Cholesterol and fatty acid'.) However, clinical trials have not supported a therapeutic role for omega-3 fatty acid supplementation in the treatment of AD: An 18-month trial of docosahexaenoic acid (DHA) supplementation in 295 patients with mild to moderate Alzheimer disease found no effect of active supplementation compared to placebo on the rate of cognitive and functional decline [50]. In a randomized, double-blind trial, 204 patients with mild to moderate AD received omega-3 fatty acid supplements (430 mg docosahexaenoic acid and 150 mg eicosapentaenoic acid, four times daily) or placebo [51]. No significant differences in cognitive decline in the two groups were observed at 12 months. MANAGEMENT ISSUES Behavioral disturbance Behavioral disturbance can profoundly affect patients with dementia as well as their families and caregivers. Recognition and treatment of delusions, hallucinations, depression, agitation, and aggression are important aspects of the care of patients with dementia. This topic is discussed separately. (See "Treatment of behavioral symptoms related to dementia".) Nutrition Inadequate nutrition is common in patients with AD and is associated with increased morbidity and mortality [52]. Interventions such as oral nutritional supplements may improve weight and fat-free mass [53]. A systematic review found that provision of high calorie supplements can help with weight gain in patients with dementia; however, the limited available data did not support a benefit in regard to functional and survival outcomes [54]. Other interventions (appetite stimulants, assisted feeding) were less clearly associated with weight gain. Tube feeding may be considered, but there is no evidence that this intervention is associated with prolonged or increased quality of life [55,56]. (See "Percutaneous endoscopic gastrostomy (PEG) tube placement: Justifying the intervention", section on 'Dementia' and "Medical care of the nursing home patient in the United States", section on 'Nutrition'.)

5 de 8

05-12-2011 22:21

Treatment of dementia

http://www.uptodate.com/contents/treatment-of-dementia?view=print

Rehabilitation Cognitive rehabilitation aims to help patients in the early stages of dementia to maintain memory and higher cognitive function and to devise strategies to compensate for declining function. Studies regarding the efficacy of this approach are limited by the lack of standardized techniques. A 2003 systematic review from the Cochrane database on cognitive rehabilitation concluded that the studies to date did not provide strong evidence for benefit with this approach, and that further research is required [57]. A subsequently published randomized study found that patients with dementia who received dual-task exercise training (eg, walking while performing calculations) improved their performance on these tasks compared to patients who did not receive this training [58]. This provides hope that cognitive remediation approaches are both feasible and of potential benefit in patients with dementia. However, it will be critical to show that improvements extend to other real life tasks before these interventions can be endorsed. Other rehabilitation approaches may offer specific benefits: Exercise programs A randomized trial in 153 community-dwelling patients with AD found that, compared with routine medical care, patients who were assigned to exercise (goal minimum of 30 minutes per day) and whose caregivers received training in managing behavioral problems had improved physical functioning and less depression [59]. In another study of 134 nursing home residents with dementia, those randomized to an individualized-exercise program demonstrated less severe decline in ADL performance over 12 months of follow-up, but had similar rates of falls, fracture, and death [60]. Occupational therapy In a randomized trial, 68 of 135 community-dwelling patients with mild to moderate dementia were assigned to receive 10 sessions of occupational therapy over five weeks [61]. Individualized therapy sessions focused on training patients and caregivers in the use of aids, coping behaviors, and other strategies to compensate for those functional deficits that were specifically problematic for the patient. Assessments of motor and process skills and activities of daily living were significantly improved compared with controls, both at six weeks and at three months, implying that the treatment has some durability. The intervention also appeared to be cost-effective, specifically reducing costs of informal care giving [62]. These multidisciplinary, nonpharmacologic approaches to management of dementia have significant advantages in having none of the side effects that significantly complicate drug treatment in this patient population. More research is needed to confirm benefits seen in these trials and to provide a standardized approach that can be applied in the general community. Patient referral Timing of referral to a specialist depends upon the comfort and knowledge base of the primary care provider in managing dementia and on the availability of specialty clinics where additional resources are available, such as social workers and neuropsychologists. Factors that would be important in considering patient referral are: uncertainty about the diagnosis of an early dementia (eg, when difficulty arises distinguishing dementia from normal aging, depression, or encephalopathy); when a non-Alzheimer dementia is likely (early and severe behavioral changes, languages problems, hallucinations or parkinsonism); when there is a young onset (<65-years-old); and when there is a strong family history. Risk factor control Aggressive identification and treatment of risk factors for stroke, cardiovascular disease, and dementia may represent an important strategy for decreasing the incidence of dementia and for slowing the progression of cognitive decline. An observational study compared the progression of Mini-Mental State Examination scores in 301 patients with AD (without cerebrovascular disease history) [63]. Patients whose vascular risk factors were treated had a slower decline in MMSE scores compared to those whose vascular risk factors were not treated. Patients with some but not all of their vascular risk factors treated had an intermediate rate of decline. However, strong support from randomized controlled clinical trials of vascular risk factor treatment in patients with dementia is lacking. A randomized study of patients with AD found that after two

6 de 8

05-12-2011 22:21

Treatment of dementia

http://www.uptodate.com/contents/treatment-of-dementia?view=print

years, progression of white matter lesions on MRI was less in those who were assigned to aggressive risk factor reduction, but clinical progression was not assessed [64]. A pilot "proof of concept" randomized clinical trial demonstrated trends toward benefit with statin treatment with atorvastatin in a 63-patient trial of mild to moderate AD [47]. However, a followup randomized clinical trial of 640 patients with mild to moderate AD found that 80 mg of atorvastatin per day did not influence cognitive endpoints after 72 weeks of treatment [65]. These topics as they relate to the incidence and prevention of dementia are discussed separately. (See "Risk factors for dementia" and "Prevention of dementia".) Survival Dementia shortens life expectancy, although actual survival estimates have varied in different reports. Length bias complicates the interpretation of many studies by failing to consider patients with rapidly progressive illness who died before they could be included in the study. In a study that adjusted for length bias, a random sample of 10,263 subjects ages 65 and older from the Canadian Study of Health and Aging were screened for dementia and followed for five years [66]. The adjusted median survival for patients with probable AD, possible AD, and vascular dementia (VaD) was 3.1, 3.5, and 3.3 years, respectively. A younger age at onset was associated with longer survival, a finding consistent with prospective follow-up of participants in the Baltimore Longitudinal Study of Aging who were age 55 years and older [67]. In this report, the median survival of patients with AD ranged from almost nine years for patients diagnosed at age 65 (an approximate 67 percent reduction in median lifespan) to approximately three years for those diagnosed at age 90 (a 39 percent reduction in median survival). These estimates will vary depending upon individual patient characteristics. While validated risk factors for reduced survival have not clearly been identified, one study suggested that the combination of wandering and falling and the presence of behavioral problems at the time of evaluation significantly adversely affected survival [68]. In contrast, comorbid conditions and disease duration did not affect survival. Where to get more information Caregivers of patients with AD can suffer significant stress, particularly as cognitive function declines. Respite care and support groups are available in most areas, often through the local agency on aging. Nationally, information can be obtained from the Alzheimer's Association at 1-800-272-3900, or on the internet (www.alz.org). Information on clinical trials in AD can be found online (www.clinicaltrials.gov); this site lists only government funded studies. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topics (see "Patient information: Dementia (including Alzheimer disease) (The Basics)") Beyond the Basics topics (see "Patient information: Dementia (including Alzheimer disease)") SUMMARY AND RECOMMENDATIONS The following recommendations are based upon our clinical practice given the existing evidence on therapies for dementia:

7 de 8

05-12-2011 22:21

Treatment of dementia

http://www.uptodate.com/contents/treatment-of-dementia?view=print

We suggest a treatment trial with a cholinesterase inhibitor for patients with mild to moderate dementia (MMSE 10-26) (Grade 2A). The choice between donepezil, rivastigmine, and galantamine can be based upon cost, individual patient tolerance, and physician experience, as efficacy appears to be similar. (See "Cholinesterase inhibitors in the treatment of dementia".) We suggest that patients with Alzheimer disease (AD) who have no significant heart disease take vitamin E (alpha-tocopherol) 1000 IU twice daily (Grade 2C). (See 'Vitamin E and selegiline' above.) In patients with moderate to advanced dementia (MMSE <17), we suggest adding memantine (10 mg twice daily) to a cholinesterase inhibitor, or using memantine alone in patients who do not tolerate or benefit from a cholinesterase inhibitor (Grade 2A). (See 'Memantine' above.) In patients with severe dementia (MMSE <10), cholinesterase inhibitors can be discontinued, but they should be restarted if the patient worsens without the medication. We recommend continuing memantine even in severe dementia, given the possibility that memantine may be disease-modifying. However, in some patients with advanced dementia it may make sense to discontinue administration of medications to maximize quality of life and patient comfort. Behavioral disturbances are common in individuals with dementia and may respond to symptomatic treatment. (See "Treatment of behavioral symptoms related to dementia".)

Use of UpToDate is subject to the Subscription and License Agreement.

2011 UpToDate, Inc. All rights reserved. | Subscription and License Agreement [ecapp0605p.utd.com-193.136.35.4-75A7B5EC0A-1426.14] Licensed to: Faculdade de Medicina da Universidade do

| Support Tag:

8 de 8

05-12-2011 22:21

S-ar putea să vă placă și