Journal of Alzheimer's Disease - Volume 15, issue 2

Authors: Shafqat, Saad

Article Type: Research Article

Abstract: Although a majority of dementia patients live in middle-income and low-income countries, dementia represents an under-recognized public health burden in the developing world. Culturally and socially, it tends to be trivialized as an inevitable consequence of aging. Economic constraints are paramount, precluding the availability of institutionalized elder care and a state-sponsored health care system. Evidence-based practice for the management of dementia is also hampered by lack of a clear-cut expert consensus on the efficacy of anti-dementia drugs. Public health education, substantial health infrastructure development, and therapeutic advances are necessary for the developing world's looming dementia crisis to be adequately tackled.

Keywords: Constraints, cultural, economic, social

DOI: 10.3233/JAD-2008-15211

Citation: Journal of Alzheimer's Disease, vol. 15, no. 2, pp. 285-287, 2008

Authors: Vellas, Bruno | Coley, Nicola | Andrieu, Sandrine

Article Type: Research Article

Abstract: Disease modifying trials are becoming increasingly common in the field of Alzheimer's disease (AD) as the search for a treatment able to slow the progression of this disease continues. In this paper, we briefly discuss the methodological considerations for disease modifying trials that were addressed during three recent international task force meetings involving specialists in the field of AD trials. Topics covered included study design, the identification of appropriate outcomes, the use of biomarkers, and the identification of suitable study populations. We also provide an update on recent disease modifying trials which have enabled us to gain experience in the …use of biomarkers and have helped to define suitable outcomes, and consider how they can help us to shape future perspectives for disease modifying trials. Show more

Keywords: Alzheimer's disease, clinical trials, dementia, disease-modifying treatment, disease progression, drug evaluation, methodology, outcomes, prevention, research design

DOI: 10.3233/JAD-2008-15212

Citation: Journal of Alzheimer's Disease, vol. 15, no. 2, pp. 289-301, 2008

Authors: Becker, Robert E. | Greig, Nigel H. | Giacobini, Ezio

Article Type: Research Article

Abstract: Alzheimer's disease (AD) drug developments and clinical trials (CT) remain vulnerable to problems that undermine research validity. Investigations of CT methods reveal how numerous factors decrease active drug-placebo group differences and increase variance, thereby reducing power to reach statistical significance for outcome measure differences in AD CTs. Such factors include, amongst many, inaccuracy, imprecision, bias, failures to follow or lack of operational protocols for applying CT methods, inter-site variance, and lack of homogeneous sampling using disorder criteria. After a review of the literature and survey of a sample of AD and Mild Cognitive Impairment (MCI) CTs, the authors question whether …problems of human error preclude AD researchers from continuing their dependence on rated outcome measures for CTs. The authors propose that the realities of AD, especially a probable irreversible progression of neuropathology prior to onset of clinical symptoms or signs capable of differentiating persons at risk for AD from normal aged, require AD investigators and clinicians to privilege biomarkers and encourage their development as surrogate targets for preventive AD treatment developments, testing, and use in clinical practice. Show more

Keywords: Alzheimer's disease, bias, biomarkers, clinical trials, errors

DOI: 10.3233/JAD-2008-15213

Citation: Journal of Alzheimer's Disease, vol. 15, no. 2, pp. 303-325, 2008

Authors: Carlsson, Cynthia M.

Article Type: Research Article

Abstract: While advances have been made in understanding the neurobiological processes underlying Alzheimer's disease (AD), few treatment options currently exist. Numerous potential therapeutic and/or preventive agents have been tested in clinical trials, yet most have failed to show a clear therapeutic benefit. The lack of effective medical therapies coupled with the incipient projected dramatic increase in the number of persons with AD in the coming decades has put medical research in a crisis to urgently find effective treatment and prevention strategies. Researchers and funding agencies have been rethinking investigative approaches in order to accelerate scientific discovery in AD therapeutics, including methodological …issues in the design and implementation of clinical trials. This review discusses lessons learned from discontinued and failed clinical trials for the treatment and prevention of AD with an emphasis on future directions of AD clinical trials. In particular, attention is given to choice of study outcome measures, participant selection and retention, and clinical trial design. While there are few treatments available for AD currently, the potential for discovery over the next decade is promising. Show more

Keywords: Alzheimer's disease, biological markers, clinical trials, cognition, neuropsychological tests

DOI: 10.3233/JAD-2008-15214

Citation: Journal of Alzheimer's Disease, vol. 15, no. 2, pp. 327-338, 2008

Authors: Iqbal, Khalid | Chohan, M. Omar | Grundke-Iqbal, Inge

Article Type: Research Article

Abstract: Development of effective neuroprotective drugs for Alzheimer's disease (AD) is a formidable challenge because this disease is multifactorial and heterogeneous. Although AD is characterized histopathologically by the presence of numerous amyloid-β plaques and neurofibrillary degeneration of abnormally hyperphosphorylated tau in the brain, these two hallmark lesions do not exist in any fixed proportion in this disease. Furthermore, in the brains of some normal aged individuals, there are as many amyloid-β plaques seen as in typical cases of AD. On the other hand, extensive neurofibrillary degeneration of abnormally hyperphosphorylated tau and dementia but in the absence of amyloid-β plaques occur in …several related neurodegenerative disorders called tauopathies. More than one molecular mechanism has been described for the development of amyloid-β as well as neurofibrillary degeneration of abnormally hyperphosphorylated tau. Thus, AD apparently results from several different etiopathogenic mechanisms and offers numerous rational therapeutic targets. We have discovered that there are at least five different subgroups of AD, and future studies are likely to identify additional subgroups. The employment of these subgroups of AD in clinical trials can markedly increase the success in developing specific and potent therapeutic drugs. Show more

Keywords: Alzheimer's disease, Alzheimer's disease subgroups, amyloid-β, Lewy bodies, neurofibrillary pathology, tau, tauopathies, ubiquitin

DOI: 10.3233/JAD-2008-15215

Citation: Journal of Alzheimer's Disease, vol. 15, no. 2, pp. 339-345, 2008

Article Type: Correction

DOI: 10.3233/JAD-2008-15216

Citation: Journal of Alzheimer's Disease, vol. 15, no. 2, pp. 347-348, 2008

Article Type: Announcement

DOI: 10.3233/JAD-2008-15217

Citation: Journal of Alzheimer's Disease, vol. 15, no. 2, pp. 349-350, 2008