Objective: Increased variability in cognition with age has been argued as an indication of pathological processes. Focusing on early detection of neurodegenerative disorders, we investigated variability in cognition in healthy middle-aged adults. In order to understand possible determinants of this variability, we also investigated associations with cognitive reserve, neuroimaging markers, subjective memory complaints, depressive symptomatology, and gender. Method: Thirty-one 50±2 years old individuals were investigated as target group and deviation was studied in comparison to a reference younger group of thirty individuals 40±2 years old. Comprehensive neuropsychological and structural imaging protocols were collected. Brain regional volumes and cortical thickness were calculated with FreeSurfer, white matter hyperintensities with CASCADE, and mean diffusivity with FSL. Results: Across-individuals variability showed greater dispersion in lexical access, processing speed, executive functions, and memory. Variability in global cognition correlated with, reduced cortical thickness in the right parietal-temporal-occipital association cortex, and increased mean diffusivity in the cingulum bundle and right inferior fronto-occipital fasciculus. A trend was also observed for the correlation between global cognition and hippocampal volume and female gender. All these associations were influenced by cognitive reserve. No correlations were found with subjective memory complaints, white matter hyperintensities and depressive symptomatology. Across-domains and across-tasks variability was greater in several executive components and cognitive processing speed. Conclusions: Variability in cognition during middle-age is associated with neurodegeneration in the parietal-temporal-occipital association cortex and white matter tracts connecting this to the prefrontal dorsolateral cortex and the hippocampus. Moreover, this effect is influenced by cognitive reserve. Studying variability offers valuable information showing that differences do not occur in the same magnitude and direction across individuals, cognitive domains and tasks. These findings may have important implications for early detection of subtle cognitive impairment and clinical interpretation of deviation from normality.

To define the profile of age-related differences in cognition in healthy middle-aged adults in order to identify the most sensitive measures of early cognitive decline. To study whether these differences precede cognitive decline in the elderly. 141 cognitively normal participants (101 middle-aged adults with age 40-50±2; and 40 elderly individuals with age 65±2) were assessed with a comprehensive neuropsychological protocol covering processing speed, attention, executive functions, verbal and visual episodic memory, procedural memory, visuoconstructive, visuoperceptive and visuospatial functions, and language. Age-related differences were detected before the age of 50 in cognitive reaction time, executive control, initial learning in verbal episodic memory, complex visuoconstructive and visuospatial functions, and lexical access. These differences preceded more extensive cognitive decline present at the age of 65. Our findings suggest subtle executive dysfunction before the age of 50, together with slowing in processing speed later on in the transition to old age. This profile could be explained by changes in the frontal lobe and its connections, starting at middle-age. These findings, together with future research, may be important for the diagnosis, prognosis, and prevention of pathological aging at a very early level.

Educational influence on cognitive performance has been extensively agreed in Neuropsychology. Nonetheless, recent studies highlighted the need of better measurements to assess benefit from the schooling experience in order to further understand schooling influence on cognition. The WAIS-III Information subtest is proposed here to measure this influence at old age. Ninety-five older adults were divided according to their educational attainment and their Information subtest score, and completed extensive neuropsychological assessment. Performance on the Information subtest had a significant effect on all same cognitive functions as educational attainment, but also on additional domains. Moreover, cognitive performance on several tasks can be classified in three levels as a function of Information score. The WAIS-III Information subtest could be of special interest as a measurement of the benefit from educational experience not only to study cognition in Spanish older populations but also heterogeneous samples in terms of educational experiences and environments.