184 Scopus citations


Background: To date, there have been no reports of individuals who have been characterized longitudinally using clinical and cognitive measures and who transitioned from cognitive normality to early symptomatic Alzheimer disease (AD) during a period when both cerebrospinal fluid (CSF) markers and Pittsburgh Compound B (PiB) amyloid imaging were obtained. Objective: To determine the temporal relationships of clinical, cognitive, CSF, and PiB amyloid imaging markers of AD. Design: Case report. Setting: Alzheimer disease research center. Participant: Longitudinally assessed 85-year-old man in a memory and aging study who was cognitively normal at his initial and next 3 annual assessments. Main Outcome Measures: Serial clinical and psychometric assessments over 6 years in addition to PiB imaging with positron emission tomography (PET) and CSF biomarker assays before autopsy. Results: Decline in measures of episodic memory and, to a lesser degree, working memory began at about age 88 years. PiB PET amyloid imaging was negative at age 88 1/2 years, but at age 89 1/2 years there was reduced amyloid β 42 and elevated levels of tau in the CSF. Beginning at age 89 years, very mild cognitive and functional decline reported by his collateral source resulted in a diagnosis of very mild dementia of the Alzheimer type. After death at age 91 years, the autopsy revealed foci of frequent neocortical diffuse amyloid β plaques sufficient to fulfill Khachaturian neuropathologic criteria for definite AD, but other neuropathologic criteria for AD were not met because only sparse neuritic plaques and neurofibrillary tangles were present. Postmortem biochemical analysis of the cerebral tissue confirmed that PiB PET binding was below the level needed for in vivo detection. Conclusion: Clinical, cognitive, and CSF markers consistent with AD may precede detection of cerebral amyloid β using amyloid imaging agents such as PiB that primarily label fibrillar amyloid β plaques.

Original languageEnglish
Pages (from-to)1557-1562
Number of pages6
JournalArchives of neurology
Issue number12
StatePublished - Dec 2009


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