VALUTAZIONE DELL'ACCURATEZZA DIAGNOSTICA DI TRE TEST PER LA MALATTIA DI ALZHEIMER: MEMORY BINDING, FREE AND CUED SELECTIVE REMINDING E DUAL TASK

UNIVERSITÀ DEGLI STUDI DI MILANO Facoltà di Medicina e Chirurgia Dipartimento di Scienze Cliniche “Luigi Sacco” SCUOLA DI DOTTORATO Scienze fisiopatologiche, neuropsicologiche e assistenziali del ciclo di vita-Ciclo XXVII Tesi di Dottorato di Ricerca: Valutazione dell’accuratezza diagnostica di tre test per la Malattia di Alzheimer: Memory Binding, Free and Cued Selective Reminding Test e Dual Task Settore Scientifico Disciplinare Med – 26 Dottorando: Dr.ssa Elena SARTORIO Matricola: R09555 Tutor: Chiar.mo Prof. Claudio MARIANI Coordinatore: Chiar.mo Prof. Roberto L. WEINSTEIN Anno Accademco 2013/2014 Background and hyphothesis The main focus of current Alzheimer’s Disease (AD) research is on early diagnosis. This emphasis has led to the proposal of new research diagnostic criteria, which stress the potential role of biomarkers[Dubois B, 2014; Jack C.R. Jr, 2011 ] in diagnosing the disease in a prodromal, or even in a preclinical stage. While a considerable amount of effort is now dedicated to crucial issues about the use of biomarkers, including the standardization of CSF analysis[Molinuevo J.L, 2014] and of neuroimaging techniques [Cure F, 2014], studies on the cognitive markers are relatively scant. This is surprising, considering that the only clinical criterion supporting the use of biomarkers in subjects with cognitive complaints is the presence of an objective cognitive dysfunction, as assessed by neuropsychological tests. Of paramount importance is the assessment of memory, as the impairment in episodic memory is most commonly seen in subjects with Mild Cognitive Impairment (MCI) who subsequently progress to a diagnosis of AD dementia[Albert M.S, 2011]. Notwithstanding the obvious relevance of this point for any validation of the proposed biomarkers, it is unfortunate that no "gold standard" is available for memory testing of AD. There is clearly the need for tests that are specific for the memory dysfunction of prodromal and early AD, and that are predictive of progression to dementia. We have identified from the literature and from our own preliminary work three tests, which appear to be promising candidates to become "gold standards" for the cognitive assessment of AD. Two tests, Short Term Memory Binding Task (STMBT) and Dual Task (DT) were developed by Human Cognitive Neuroscience, Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, UK. The first is the STMBT. The impairment of the mechanisms responsible for holding integrated objects in verbal short-term memory was shown to be selectively impaired in mild and moderate AD, in comparison to healthy ageing [Brockmole, J.R., 2008] and chronic depression in the elderly [Parra MA, 2010]. The second is the DT [Baddeley A, 1986; Baddeley A, 1991, Della Sala S, 2010]. Performance on the DT has been shown to effectively discriminate AD from healthy aging and depression [Kaschel R]. Task performance appears to be preserved in subjects with a diagnosis of MCI, suggesting that the test is suitable to map disease progression, rather than for early diagnosis [Foley J.A, 2011]. The third test is the FCSRT [Grober E,1988]. This traditional memory test has been proposed to have high predictive value for the progression of isolated disorders of memory towards AD. In particular, Dubois and colleagues [Dubois B, 2007] have claimed that episodic memory loss of the hippocampal type (characterised by a free recall deficit on testing not normalised with cueing) may be the defining feature of prodromal AD. This hypothesis is supported by a study, which indicated the predictive role of defective performance on the FCSRT on progression to dementia in subjects fulfilling the criteria for MCI [Sarazin M., 2007]. Metodolo