Neuropsychological and neurobiological markers of the preclinical stage of Alzheimer's disease

ABSTRACT

Dementia, especially Alzheimer's disease, has a high prevalence in the elderly population. Therefore, identifying individuals who are at a high risk for early diagnosis is crucial to allow both pharmacological and behavioral therapeutic interventions, which in some cases can delay the progression of dementia. This paper describes neuropsychological and neurobiological markers for the early diagnosis of Alzheimer's disease and presents the main risk factors, including neuropathological, neuroanatomical, neurofunctional, genetic, and neuropsychological. The literature shows that the combination of these markers is the best method for predicting Alzheimer's disease, years before its clinical manifestation. The most prevalent neurobiological and neuropsychological risk factors include (1) senile plaques and neurofibrillary tangles in the medial temporal lobe and cortical regions, (2) low concentrations of Aâ1-42 peptide and high concentrations of total tau protein and phosphorylated tau protein in cerebrospinal fluid, (3) reduced global cerebral volume, increased ventricular volume, and atrophy in the hippocampal formation and entorhinal cortex, (4) global reductions in cerebral metabolism and perfusion in the temporoparietal junction, temporal, parietal, and frontal lobes, hippocampal formation, and posterior cingulate cortex, (5) the presence of the apolipoprotein E å4 allele, and (6) verbal anterograde episodic long-term memory impairment and executive dysfunction. The present review discusses the evidence for markers that identify individuals who are at a high risk of developing Alzheimer's disease and the importance of longitudinal studies in this context.