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Background: Chronic inflammation has been linked to memory and other cognitive impairments, as well as Alzheimer's disease. Here, we investigate the association between inflammatory markers and changes in brain activity measured by regional cerebral blood flow (rCBF) to assess the relationship between inflammation and brain function in older individuals., Methods: Annual 15O water resting-state positron emission tomography (PET) scans collected over a 5-year period were assessed in 138 cognitively normal older participants (77 males; mean age at baseline = 71.3; mean scans per participant = 3.5) in the Baltimore Longitudinal Study of Aging. Voxel-wise linear mixed models were used to investigate associations between rCBF and C-reactive protein (CRP) and interleukin-6 (IL-6) at the time of scanning. We examined relationships between baseline CRP and IL-6 levels and baseline rCBF, and relationships between baseline and mean inflammatory levels over time and longitudinal rCBF changes., Results: Higher baseline CRP and IL-6 were each associated with lower baseline rCBF primarily in frontal and occipital regions, with only the lingual gyrus surviving atrophy correction. Higher baseline and mean CRP were also associated with greater rCBF declines over time in anterior cingulate and hippocampal regions, whereas higher baseline and mean IL-6 levels were associated with greater rCBF declines in orbitofrontal and hippocampal regions., Conclusions: Higher levels of inflammation are associated with longitudinal changes in brain function in regions important for cognition. These results, along with previous studies, suggest that chronic inflammation in older adults may contribute to age-associated declines in cognitive function.

To develop targeted intervention strategies for the treatment of Alzheimer's disease, we first need to identify early markers of brain changes that occur before the onset of cognitive impairment. Here, we examine changes in resting-state brain function in humans from the Baltimore Longitudinal Study of Aging. We compared longitudinal changes in regional cerebral blood flow (rCBF), assessed by (15)O-water PET, over a mean 7 year period between participants who eventually developed cognitive impairment (n = 22) and those who remained cognitively normal (n = 99). Annual PET assessments began an average of 11 years before the onset of cognitive impairment in the subsequently impaired group, so all participants were cognitively normal during the scanning interval. A voxel-based mixed model analysis was used to compare groups with and without subsequent impairment. Participants with subsequent impairment showed significantly greater longitudinal rCBF increases in orbitofrontal, medial frontal, and anterior cingulate regions, and greater longitudinal decreases in parietal, temporal, and thalamic regions compared with those who maintained cognitive health. These changes were linear in nature and were not influenced by longitudinal changes in regional tissue volume. Although all participants were cognitively normal during the scanning interval, most of the accelerated rCBF changes seen in the subsequently impaired group occurred within regions thought to be critical for the maintenance of cognitive function. These changes also occurred within regions that show early accumulation of pathology in Alzheimer's disease, suggesting that there may be a connection between early pathologic change and early changes in brain function.

This article investigates longitudinal imaging characteristics of early cognitive decline during normal aging, leveraging on high-dimensional imaging pattern classification methods for the development of early biomarkers of cognitive decline. By combining magnetic resonance imaging (MRI) and resting positron emission tomography (PET) cerebral blood flow (CBF) images, an individualized score is generated using high-dimensional pattern classification, which predicts subsequent cognitive decline in cognitively normal older adults of the Baltimore Longitudinal Study of Aging. The resulting score, termed SPARE-CD (Spatial Pattern of Abnormality for Recognition of Early Cognitive Decline), analyzed longitudinally for 143 cognitively normal subjects over 8 years, shows functional and structural changes well before (2.3-2.9 years) changes in neurocognitive testing (California Verbal Learning Test [CVLT] scores) can be measured. Additionally, this score is found to be correlated to the [(11)C] Pittsburgh compound B (PiB) PET mean distribution volume ratio at a later time. This work indicates that MRI and PET images, combined with advanced pattern recognition methods, may be useful for very early detection of cognitive decline., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Subjective cognitive complaints are often used in the diagnosis of memory and other cognitive impairment. This study examined whether cognitive complaints are associated with longitudinal changes in cognition and cross-sectional differences in regional brain function during memory performance in 98 participants with a mean age of 75., Method: The Cognitive Failures Questionnaire (CFQ) assessed cognitive complaints and mixed effects regression models were used to determine whether mean CFQ scores predicted rates of change in cognitive function over a period of 11.5 years., Results: Higher CFQ scores, reflecting increased subjective complaints, were associated with steeper rates of decline in immediate and delayed recall on the California Verbal Learning Test. Voxel-based regression analysis was used to determine the cross-sectional relationship between CFQ scores and regional cerebral blood flow measured by PET during a resting condition and during verbal and figural memory tasks. Higher levels of cognitive complaints were associated with increased activity in insular, lingual and cerebellar areas during memory tasks., Conclusions: These findings offer some support for the validity of subjective cognitive complaints as markers of age related changes in memory and brain activity., ((c) 2010 APA, all rights reserved.)