Dementia study

The anxiety disorders are common and surprisingly disabling conditions. Studies on the health economics of generalized anxiety disorder, panic disorder, social anxiety disorders and obsessive compulsive disorder document the cost to the individual and to society. Attention has focused on the major psychiatric disorders such as depression, schizophrenia and the dementias. Studies suggest that many anxiety disorders are of early onset and too often chronic they are quite common and impose a heavy burden on society. More studies will be needed to discern the fine grain in the survey material and to identify more precisely the location and type of societal costs. These factors will vary from country to country, from district to district, between men and women and between various age groups. 

Van Dijk EJ, Breteler MM, Schmidt R, Berger K, Nilsson LG, Oudkerk M, Pajak A, Sans S, de Ridder M, Dufouil C, Fuhrer R, Giampaoli S, Launer LJ, Hofman A CASCADE Consortium (2004) The association between blood pressure, hypertension, and cerebral white matter lesions cardiovascular determinants of dementia study. Hypertension 44 625-630... 

Black S, Roman GC, Geldmacher DS, Salloway S, Hecker J, Burns A, Perdomo C, Kumar D, Pratt R Donepezil 307 Vascular Dementia Study Group. Efficacy and tolerability of donepezil in vascular dementia positive results of a 24-week, multicenter, international, randomized, placebo-con-trolled clinical trial. Stroke 2003 34(10) 2323-30. 

Acetyl-i-carnitine (4) is marketed in Italy for dementia as of this writing it is also in Phase III clinical trials in the United States and Europe. In a double-blind, placebo-controUed clinical trial over a one-year period involving 130 patients with clinically diagnosed AD, a slower rate of deterioration in 13 of the 14 outcome measures was observed in the dmg-treated group (28). Earfler smaller scale pilot studies in demented patients had also shown some improvement of various behavioral and cognitive functions (29). 

Other nootropic agents in some stage of clinical development include nebracetam (9), nefinacetam (10), and BMY 21502 (11). Nebracetam, an aminomethyl pyrrolidinone derivative, is expected to be approved in Japan in 1994 (73). In clinical studies involving patients having cerebrovascular or senile dementia of the Alzheimer s type, clinical symptoms such as spontaneous or emotional expression were enhanced in up to 71% of cases. Long-term treatment using nebracetam in patients with cerebral infarction also afforded marked improvement in most cases with few side effects (74). A review of this compound has beenpubUshed (75). 

There appear to be a number of clinical studies that support the efficacy of various nootropic agents in patients with some form or degree of dementia, but the results are not particularly convincing (50,51,57—59,63,74). 

The anainoacridines, tacrine (19) and its 1-hydroxy metaboUte, velnacrine (20), are reversible inhibitors of AChE. Tacrine was synthesi2ed in the 1940s and has been used clinically for the treatment of myasthenia gravis and tardive dyskinesia (115). Placebo-controUed studies have indicated modest efficacy of tacrine to treat AD dementia (122,123) and in 1993 the dmg was recommended for approval by the PDA under the trade name Cognex. Tacrine (19) has been shown to interact with sites other than AChE, such as potassium channels (124) and muscarinic receptors. However, these interactions are comparatively weak and are not thought to contribute to the biological activity of the dmg at therapeutic levels (115). 

For some mental health problems such as severe dementia, effectiveness might actually be achieved by slowing down a deteriorative trend or accelerating an upward trend. This makes effectiveness difficult to assess without a control or comparison group, or a set of norms, and emphasizes why naturalistic studies alone are rarely sufficient as an evidence base for clinical or policy decisions. 

A number of economic studies have been published that assess the economic impact of the introduction of anticholinesterase drugs on the care for people with dementia. Overall, they suggest that the introduction of the new drugs might be cost-neutral, while leading to modest improvements in the health-related quality of life of patients and carers. However, the reliability and robustness of the economic evidence need to be considered before concluding that any additional benefits of the new dmgs for dementia are indeed worth the cost. 

Economic studies should consider the costs of all the resources and services used in the process of care. In addition, the outcomes that are a consequence of the health or social care interventions evaluated need to be included. For dementia, these include the costs of hospital inpatient and out-patient care, primary and community-based health-care services, social welfare services, and care provided by voluntary agencies or by femily and friends. Ideally, a broad perspective reflecting the costs and outcomes to society should be adopted. As a minimum, the perspective of the analysis should include the costs and outcomes to key health and social care providers or funders and to patients and their families. 

One study used quality-adjusted life years to capture the range of health-related dimensions that may affect the quality of life of patients. This measure also provides an estimate of the value or preferences for changes in health status (Neumann et al, 1999). The study used the Health Utility Index Mark II in a sample of patients and carers, which is a generic measure of the value of health-related quality of life. However, it is clear that further research is needed to explore (a) the key determinants or dimensions of quality of life that are important to people with dementia and their carers (b) whether existing instmments to measure and value health-related quality of life are able to detect differences in quality of life that are important to people with cognitive disability and their carers and (c) whether the assessment and... 

Care for people with dementia is demanding of resources, while the outcomes of care are uncertain. To date, the economic analyses of care strategies have been limited to new drug therapies for people with Alzheimer s disease. Full economic evaluations to compare both the costs and consequences have only been conducted for one of these dmgs, donepezil. However, problems with the design and data used in these studies mean that they do not provide robust evidence to determine appropriate management strategies for dementia. 

Asare E, Dunn G, Glass J, McArthur J, Luthert P, Lantos P, EveraU I (1996) Neuronal pattern correlates with the severity of human immunodeficiency virus-associated dementia complex. Usefulness of spatial pattern analysis in clinicopathological studies. Am J Pathol 148(l) 31-38... 

McArthur JC (2004) HIV dementia an evolving disease. J Neuroimmunol 157(l-2) 3-10 McArthur JC, Hoover DR, BaceUar H, MUler EN, Cohen BA, Becker JT, Graham NM, McArthur JH, Seines OA, Jacobson LP et al (1993) Dementia in AIDS patients incidence and risk factors. Multicenter AIDS Cohort Study. Neurology 43(ll) 2245-2252 McManus CM, liu JS, Hahn MT, Hua LL, Brosnan CE, Berman JW, Lee SC (2000) Differential induction of chemokines in human microgUa by type I and II interferons. GUa 29(3) 273-280 McQuibban GA, Butler GS, Gong JH, BendaU L, Power C, Clark-Lewis I, OveraU CM (2001) Matrix metaUoproteinase activity inactivates the CXC chemokine stromal ceU-derived factor-1. J Biol Chem 276(47) 43503 3508... 

Rostasy K, Egles C, Chauhan A, Kneissl M, Bahrani P, Yiannoutsos C, Hunter DD, Nath A, Hedreen JC, Navia BA (2003) SDE-lalpha is expressed in astrocytes and neurons in the AIDS dementia complex an in vivo and in vitro study. J Neuropathol Exp Neurol 62(6) 617-626... 

Brengel-Pesce K, Innocenti-Francillard P, Morand P, Chanzy B, Seigneurin JM (1997) Transient infection of astrocytes with HIV-1 primary isolates derived from patients with and without AIDS dementia complex. J Neurovirol 3 449-454 Budka H, Costanzi G, Cristina S, Lechi A, Parravicini C, Trabattoni R, Vago L (1987) Brain pathology induced by infection with the human immunodeficiency virus (HIV). A histological, immunocytochemical, and electron microscopical study of 100 autopsy cases. Acta Neuropathol (Berl) 75 185-198... 

McArthur JC, Hoover DR, Bacellar H, Miller EN, Cohen BA, Becker JT, Graham NM, McArthur JH, Seines OA, Jacobson LP et al (1993) Dementia in AIDS patients incidence and risk factors. Multicenter AIDS Cohort Study. Neurology 43(ll) 2245-2252... 

Treatment of neurons with dualtropic X4R5 gpl20 has been shown to induce cytochrome c accumulation and caspase 9, 8, and 3 activation (Garden et al. 2002). Incidentally in the same studies, activated caspase 3 immunoreactivity was found in the brains of neuroAIDS patients. Furthermore, caspase 3 activation was found to be involved in the synaptic and dendritic injury (Garden et al. 2002). Chronic dendritic disrnption has been correlated with the severity of HIV-related dementia (as reviewed in Ellis et al. 2007). 

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