title: Neuropsychological predictors of rapidly progressive Alzheimer's disease.
abstract: OBJECTIVE
  Alzheimer's disease (AD), the most common cause of dementia, typically shows a slow clinical progression over time. 'Rapidly progressive' AD, a variant of the disease characterized by an aggressive course, exhibits distinct clinical, biological, and neuropathological features. Here, we investigate neuropsychological predictors of rapid decline in a group of mild patients with AD.
  
  
  METHODS
  One hundred fifty-three mild patients with AD admitted to a memory disorder clinic and followed for up to 3 years were included in this study. A comprehensive neuropsychological (NP) battery was performed at the time of enrollment. Patients were defined as 'rapidly progressive' if they exhibited a drop of 6 or more points on the Mini Mental State Examination (MMSE) between two consecutive annual visits. This event defined the main outcome in multiple analyses of variance and Cox proportional hazards models that investigated the impact of NP predictors. Categorical principal component analysis (CATPCA) was also employed in order to delineate clusters of NP tests and to test their effect on the outcome.
  
  
  RESULTS
  Of 153 subjects, thirty-seven (24%) were classified as 'rapidly progressive'; those subjects showed younger age of symptoms onset compared to slow decliners (68 vs 71.5 years old). Baseline lower performance on a neuropsychological test of naming predicted a rapid decline over the follow-up (P = 0.001). Three clusters of NP were defined by CATPCA: (i) executive/language, (ii) visuospatial memory, and (iii) verbal memory. The executive/language component predicted a rapid decline over the follow-up (P = 0.016).
  
  
  CONCLUSIONS
  Early executive/language impairment is highly predictive of a rapid progression of AD.
authors.affiliation: Memory Clinic, Department of Neurology and Psychiatry, 'La Sapienza' University, Rome, Italy.|Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: G
authors.initials: G
authors.lastname: Tosto
authors.affiliation: Memory Clinic, Department of Neurology and Psychiatry, 'La Sapienza' University, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Gasparini
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Brickman
authors.affiliation: Memory Clinic, Department of Neurology and Psychiatry, 'La Sapienza' University, Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Letteri
authors.affiliation: Memory Clinic, Department of Neurology and Psychiatry, 'La Sapienza' University, Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Renie'
authors.affiliation: Department of Cell Biology and Neuroscience, National Institute of Health, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Piscopo
authors.affiliation: Memory Clinic, Department of Neurology and Psychiatry, 'La Sapienza' University, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Talarico
authors.affiliation: Memory Clinic, Department of Neurology and Psychiatry, 'La Sapienza' University, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Canevelli
authors.affiliation: Department of Cell Biology and Neuroscience, National Institute of Health, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Confaloni
authors.affiliation: Memory Clinic, Department of Neurology and Psychiatry, 'La Sapienza' University, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bruno
mesh_terms: D017668:Age of Onset; D000368:Aged; D000375:Aging / Q000523:psychology; D000544:Alzheimer Disease / Q000523:psychology*; D018450:Disease Progression; D056344:Executive Function; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007802:Language; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000523:psychology; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D016019:Survival Analysis
keywords: categorical principal component analysis; executive functions; language functions; rapidly progressive Alzheimer's disease