Methodological Issues in Primary Prevention Trials for Neurodegenerative Dementia
Authors: Andrieu, Sandrine | Coley, Nicola | Aisen, Paul | Carrillo, Maria C. | DeKosky, Steven | Durga, Jane | Fillit, Howard | Frisoni, Giovanni B. | Froelich, Lutz | Gauthier, Serge | Jones, Roy | Jönsson, Linus | Khachaturian, Zaven | Morris, John C. | Orgogozo, Jean-Marc | Ousset, Pierre-Jean | Robert, Philippe | Salmon, Eric | Sampaio, Cristina | Verhey, Frans | Wilcock, Gordon | Vellas, Bruno
Article Type: Review Article
Abstract: The prevention of neurodegenerative dementias, such as Alzheimer's disease, is a public health priority. Due to the large numbers of affected patients, even interventions bringing about a relatively small delay in disease onset could have large public health effects. Randomized controlled trials (RCTs) are required to demonstrate the effectiveness of preventive interventions, but such trials raise specific methodological questions because they are new in the field of neurodegenerative diseases, and require large numbers of elderly subjects and lengthy follow-up periods. We performed a literature search to identify primary prevention RCTs for neurodegenerative dementia. The methodology of the trials was summarized …and discussed during two expert meetings. Overall, 39 trials were identified that assessed dementia incidence or cognitive decline as a primary or secondary study outcome. Age was the most common selection criteria for target populations. Follow-up periods ranged from one month to nine years and were longest in studies measuring dementia incidence as an outcome. Results of RCTs have so far been generally negative and conflicting with those of observational studies, perhaps due to methodological issues. Future trials must therefore carefully consider the target population, outcomes and duration of follow-up to be used, and should assess the problem of attrition. Show more
Keywords: Alzheimer's disease, clinical trials, clinical trials methodology, cognitive aging, cognitive decline, dementia, prevention trials, study design
DOI: 10.3233/JAD-2009-0971
Citation: Journal of Alzheimer's Disease, vol. 16, no. 2, pp. 235-270, 2009
Evolving Evidence for the Value of Neuroimaging Methods and Biological Markers in Subjects Categorized with Subjective Cognitive Decline
Authors: Lista, Simone | Molinuevo, Jose L. | Cavedo, Enrica | Rami, Lorena | Amouyel, Philippe | Teipel, Stefan J. | Garaci, Francesco | Toschi, Nicola | Habert, Marie-Odile | Blennow, Kaj | Zetterberg, Henrik | O’Bryant, Sid E. | Johnson, Leigh | Galluzzi, Samantha | Bokde, Arun L.W. | Broich, Karl | Herholz, Karl | Bakardjian, Hovagim | Dubois, Bruno | Jessen, Frank | Carrillo, Maria C. | Aisen, Paul S. | Hampel, Harald
Article Type: Review Article
Abstract: There is evolving evidence that individuals categorized with subjective cognitive decline (SCD) are potentially at higher risk for developing objective and progressive cognitive impairment compared to cognitively healthy individuals without apparent subjective complaints. Interestingly, SCD, during advancing preclinical Alzheimer’s disease (AD), may denote very early, subtle cognitive decline that cannot be identified using established standardized tests of cognitive performance. The substantial heterogeneity of existing SCD-related research data has led the Subjective Cognitive Decline Initiative (SCD-I) to accomplish an international consensus on the definition of a conceptual research framework on SCD in preclinical AD. In the area of biological markers, the …cerebrospinal fluid signature of AD has been reported to be more prevalent in subjects with SCD compared to healthy controls; moreover, there is a pronounced atrophy, as demonstrated by magnetic resonance imaging, and an increased hypometabolism, as revealed by positron emission tomography, in characteristic brain regions affected by AD. In addition, SCD individuals carrying an apolipoprotein ɛ 4 allele are more likely to display AD-phenotypic alterations. The urgent requirement to detect and diagnose AD as early as possible has led to the critical examination of the diagnostic power of biological markers, neurophysiology, and neuroimaging methods for AD-related risk and clinical progression in individuals defined with SCD. Observational studies on the predictive value of SCD for developing AD may potentially be of practical value, and an evidence-based, validated, qualified, and fully operationalized concept may inform clinical diagnostic practice and guide earlier designs in future therapy trials. Show more
Keywords: Alzheimer’s disease, biological markers, blood-based biomarkers, cerebrospinal fluid biomarkers, clinical trials, functional MRI markers, molecular imaging markers, preclinical Alzheimer’s disease, structural MRI markers, subjective cognitive decline
DOI: 10.3233/JAD-150202
Citation: Journal of Alzheimer's Disease, vol. 48, no. s1, pp. S171-S191, 2015