Amyloid positron emission tomography and cognitive reserve

Abstract

Alzheimer's disease (AD) is characterized by a non-linear progressive course and several aspects influence the relationship between cerebral amount of AD pathology and the clinical expression of the disease. Brain cognitive reserve (CR) refers to the hypothesized capacity of an adult brain to cope with brain damage in order to minimize symptomatology. CR phenomenon contributed to explain the disjunction between the degree of neurodegeneration and the clinical phenotype of AD. The possibility to track brain amyloidosis (Aβ) in vivo has huge relevance for AD diagnosis and new therapeutic approaches. The clinical repercussions of positron emission tomography (PET)-assessed Aβ load are certainly mediated by CR thus potentially hampering the prognostic meaning of amyloid PET in selected groups of patients. Similarly, amyloid PET and cerebrospinal fluid amyloidosis biomarkers have recently provided new evidence for CR. The present review discusses the concept of CR in the framework of available neuroimaging studies and specifically deals with the reciprocal influences between amyloid PET and CR in AD patients and with the potential consequent interventional strategies for AD.

Keywords: Alzheimer disease; Amyloid positron emission tomography; Brain; Cognitive reserve; Mild cognitive impairment.

Figures

Figure 1

Schematic representation of the possible mechanisms mediating the effect of cognitive reserve on the onset of Alzheimer’s dementia and corresponding expected results on 18F-FDG and amyloid positron emission tomography. According to hypothesis (A) cognitive reserve (CR) would simply delay the clinical expression of the disease. In fact despite amyloid positron emission tomography (PET) and FDG PET marked positivity patients are able to delay symptoms thanks to compensative functional networks and/or structural features such as larger temporal lobe volume[14,51]. Hypothesis (B) admits an opposite scenario in which, CR would prevent/delay amyloid deposition and Alzheimer’s dementia (AD) pathology and thus neuronal damage and dementia onset[17]. Finally hypothesis (C) could coexist with either of the first two and would explain the effect of CR as a sort of brain resilience despite AD pathology thus allowing a relatively preserved 18F-FDG PET scan for a longer period of time[59]. Amy-PET: Amyloid PET; ++: Markedly positive scan; +: Positive scan; -: Negative/relatively preserved scan.