Predictive Biomarkers of Cognitive Decline

Dear Colleagues, 

Alzheimer’s disease (AD) is the most common neurodegenerative disease among the elderly with a progressive decline in cognitive function significantly affecting quality of life. Both the prevalence and emotional and financial burdens of AD on patients, their families, and society are predicted to grow significantly in the near future, due to a prolongation of the average human lifespan. Several lines of evidence suggest that modifications of risk-enhancing lifestyles and initiation of pharmacological and non-pharmacological treatments in the early stage of disease, although not able to modify its course, help to maintain personal autonomy in daily activities and significantly reduce the total costs of disease management. Moreover, many clinical trials with potentially disease-modifying drugs are devoted to the prodromal stages of AD. Thus, the identification of markers of conversion from the prodromal form to clinical AD may be crucial for developing strategies of early interventions. PET amyloid imaging has initially been considered as the main tool to investigate the beginning of the AD process in cognitively intact individuals. The percentage of PET-amyloid-positive controls is of 6% at age 60 but reaches 50% at age 90 in community-based samples, pointing to the fact that amyloid deposition (as amyloid plaque formation) is closely related to the aging process. Compared with amyloid-negative, amyloid-positive controls showed moderate decline in verbal and visual episodic memory over 36 months but no changes in non-memory functions. Most importantly, the absence of amyloid in MCI cases is associated with cognitive stability at 36 months. Increased amyloid binding is associated with brain atrophy, cortical thinning, but also decreased cortical metabolism, aberrant functional connectivity at rest and decreased task-related deactivation of the default mode network. Altogether, these data suggest that, in contrast to CSF Aß and tau changes that signal a biological diathesis to neurodegeneration, amyloid positivity in the human brain is present as a part of the aging process, representing a critical step preceding the installation of AD pathophysiology. However, not all cases with elevated amyloid bindings evolve to AD and several cases develop dementia not necessarily related to amyloid aggregation. Age, education, APOE4, vascular burden score, but also baseline cognitive performances and hippocampal volume have all been used as predictive variables in AD progression models that primarily include amyloid and tau uptake at baseline and, in some cases, amyloid and tau slope over time. The relative weight of these additional parameters in the progression of asymptomatic at-risk and preclinical AD cases is still a matter of debate. In recent years, several lines of evidence have supported the idea that psychological and lifestyle factors such as personality, nutrition, and level of physical exercise in middle age may have significant neuroprotective benefits. The objective of this proposed Special Issue on “Predictive Biomarkers of Cognitive Decline” is to publish updated and cutting-edge scientific findings as well as systematic reviews and meta-analyses on the proposed predictive biomarkers of cognitive decline in healthy controls and persons with initial cognitive decrement, including imaging, plasma and CSF candidates but also psychological and lifestyle modifiers.

Prof. Dr. Panteleimon Giannakopoulos
Guest Editor

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• Alzheimer’s disease (AD)
• cognitive decline
• biomarkers
• PET amyloid imaging
• predictive variables
• imaging