These data demonstrate the feasibility of differentiating underlying pathologic processes responsible for cognitive decline in the preclinical disease state and suggest that further refinement in diagnostic criteria may allow more accurate early detection of prodromal DLB and AD

These data demonstrate the feasibility of differentiating underlying pathologic processes responsible for cognitive decline in the preclinical disease state and suggest that further refinement in diagnostic criteria may allow more accurate early detection of prodromal DLB and AD. Keywords:Mild cognitive impairment, Alzheimers disease, Dementia with Lewy bodies == 1. disease, Dementia with Lewy bodies == 1. Introduction == The clinical phenotype of early, predementia, dementia with Lewy bodies (DLB) is unknown. Early clinical changes that predate the development of a symptom complex sufficient to meet DSM-IV criteria for dementia likely occur in all slowly progressive degenerative disease states, such as Alzheimers disease (AD) and ML-323 DLB (Busse et al., 2003,2006;Jicha and Petersen, 2007;Lambon Ralph et al., 2003;Panza et al., 2007;Petersen, 2007;Winblad et al., 2004). The early predementia clinical state of AD, characterized by amnestic difficulties, is embodied by the proposed diagnostic criteria of mild cognitive impairment (MCI-AD) (Jicha and Petersen, 2007;Petersen, 2007;Winblad et al., 2004). While there is much debate as to the usefulness and specific criteria for the diagnosis of MCI, the recognition that such a clinical entity exists has spurred research into the early predementia detection of AD. Such research endeavors have proved useful in the identification of individuals at risk for the development of AD (Bruscoli and Lovestone, 2004;Chong and Sahadevan, 2005;Griffith et al., 2006;Modrego, 2006;Petersen, 2007;Petersen et al., 1999,2001;Winblad et ML-323 al., 2004). These discoveries have allowed the development of the first wave of secondary prevention trials for AD (Petersen et al., 2005). Elucidation of the predementia, clinical Rabbit Polyclonal to GNA14 phenotype of DLB (MCI-DLB) may be similarly useful in the study of the clinical progression of disease, and allow early therapeutic intervention for persons with DLB. Lewy body pathology (LBP) is found in the postmortem brain of all individuals who have suffered from Parkinsons disease (PD) and DLB. LBP is also seen in some cases of AD (termed the Lewy body variant of AD, LBV), and in the brains of normal persons who have been autopsied (Del Tredici et al., 2002;Dickson, 2002;Lippa et al., 1994;McKeith et al., 2004;McKeith, 2006;Parkkinen et al., 2005). The latter observation suggests that the pathological features of DLB may predate clinical diagnosis in many cases. It further supports the rationale for ML-323 early, clinical, predementia detection of disease states related to the pathological development of LBP in the brains of affected individuals. The clinical phenotype of DLB is characterized by the presence of at least two of the three core clinical criteria: (1) Parkinsonism; (2) early hallucinations, delusions, and paranoia; and (3) severe fluctuations in cognitive state. The diagnosis of DLB is also supported by the findings of: (1) depression, (2) hypersensitivity to neuroleptics, and (3) REM sleep behavior disorder (RBD) (McKeith, 2006). While these features can also be seen in other pathological disease states such as AD, early manifestation of these symptoms raises the index of suspicion of DLB in the discerning clinician. A diagnosis of Parkinsons disease that predates the development of cognitive or psychiatric symptoms by more than 1 year shifts the diagnosis from DLB to PD dementia (PDD) (Lippa et al., 2007;McKeith, 2006). Although there remains some debate as to the validity of such distinction, diagnostic criteria seeking to establish uniformity between clinicians have supported this approach (Lippa et al., 2007;McKeith, 2006). The determination of the degree of Parkinsonism necessary to shift the clinical diagnosis is purely subjective (Lippa et al., 2007;Louis and Bennett, 2007). The clinical acuity, methods, and operational definition used to determine a diagnosis of Parkinsonism may differ significantly between clinicians and centers (Lippa et al., 2007). Likewise, early psychiatric features of DLB are often attributed to primary psychiatric conditions and fluctuations to medical illness. Mild Parkinsonism, psychiatric features, and hallucinations can be seen in many individuals that do not exhibit the hallmark pathological features of DLB at autopsy. It is unclear to what degree these clinical features are predictive of pathological DLB in the predementia disease state. The neuropsychological profile of clinical DLB is characterized by prominent involvement of frontal attentional/executive and parieto-occipital visuospatial pathways (Collerton et al., 2003;Crowell et al., 2007;Ferman and Boeve, 2007;Ferman et al., 2006;Guidi et al., 2006;Hanyu et al., 2006;McKeith, 2006;Metzler-Baddeley, 2007;Mondon et al., 2007;Preobrazhenskaya et al., 2006;Williams et al., 2007). The clinical profile of predementia DLB has not been elucidated, but is likely to involve these same neuroanatomic areas, albeit to a lesser degree. The present study uses prospectively collected clinical data to examine the clinical top features of neuropathologically proved DLB situations in the first, predementia scientific disease state. The results support the hypothesis that MCI-DLB could be differentiated and discovered from MCI-AD, years before scientific dementia is obvious..