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Cognitive abilities decline with age, but with considerable individual variation. The neurobiological correlate of this variation is not well described. Functional brain imaging studies have demonstrated reduced task-induced deactivation (TID) of the brain's default mode network (DMN) in a wide range of neurodegenerative diseases involving cognitive symptoms, in conditions with increased risk of Alzheimer's disease, and even in advanced but healthy aging. Here, we investigated brain activation and deactivation during a visual-motor task in 185 clinically healthy males from a Danish birth cohort, whose cognitive function was assessed in youth and midlife. Using each individual as his own control, we defined a group with a large degree of cognitive decline, and a control group. When correcting for effects of total cerebral blood flow and hemoglobin level, we found reduced TID in the posterior region of the DMN in the cognitive decline group compared to the control group. Furthermore, increased visual activation response was found in the cognitive decline group, indicating that the TID reduction was not exclusively due to overall impaired vascular reactivity. These results suggest a neurobiological basis for subclinical cognitive decline in late midlife, which includes TID alterations similar to the pattern seen in patients with AD and mild cognitive impairment. Hence, TID reduction might be suggested as an early marker for subtle cognitive decline in aging., (Copyright © 2014 Wiley Periodicals, Inc.)

Abstract: Human neuroimaging studies have well demonstrated the presence of a “default system” in the brain, which shows a “default mode of brain activity”, i.e., greater activity during the resting state than during an attention-demanding cognitive task. The default system consists mainly of the medial prefrontal and medial parietal areas. It has been proposed that this default activity is concerned with internal thought processes. Here, I first describe activities observed in the human default system measured by several methods, in relation task performance, development, aging and psychiatric disorder. I will then introduce recent nonhuman primate studies that indicate correlated low-frequency spontaneous brain activity within the default system, high metabolic levels in these medial brain areas during rest and task-induced suppression of neuronal activity in the medial parietal area. Furthermore, I will present our data in which we found task-induced deactivation in the monkey default system, and will examine similarities and differences in default activity between the human and nonhuman primate. Finally, I will discuss the functional significance of the default system and consider the possibility of internal thought processes in the monkey. [Copyright &y& Elsevier]

Alzheimer's disease (AD) is the most common form of dementia in old age, and is characterized by prominent impairment of episodic memory. Recent functional imaging studies in AD have demonstrated alterations in a distributed network of brain regions supporting memory function, including regions of the default mode network. Previous positron emission tomography studies of older individuals at risk for AD have revealed hypometabolism of association cortical regions similar to the metabolic abnormalities seen in AD patients. In recent functional magnetic resonance imaging (fMRI) studies of AD, corresponding brain default mode regions have also been found to demonstrate an abnormal fMRI task-induced deactivation response pattern. That is, the relative decreases in fMRI signal normally observed in the default mode regions in healthy subjects performing a cognitive task are not seen in AD patients, or may even be reversed to a paradoxical activation response. Our recent studies have revealed alterations in the pattern of deactivation also in elderly individuals at risk for AD by virtue of their APOE e4 genotype, or evidence of mild cognitive impairment (MCI). In agreement with recent reports from other groups, these studies demonstrate that the pattern of fMRI task-induced deactivation is progressively disrupted along the continuum from normal aging to MCI and to clinical AD and more impaired in e4 carriers compared to non-carriers. These findings will be discussed in the context of current literature regarding functional imaging of the default network in AD and at-risk populations. [ABSTRACT FROM AUTHOR]