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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.

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 ϭ 22) and those who remained cognitively normal (n ϭ 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.

Background and Purpose-Changes in patterns of regional cerebral blood flow (rCBF) were assessed over a period of 6 years in 14 treated hypertensive participants (HTNs) and 14 age-matched healthy older participants (healthy controls [HCs]) in the Baltimore Longitudinal Study of Aging. Methods-Resting-state PET scans collected at years 1, 3, 5, and 7 were used to determine differences in longitudinal patterns of rCBF change in HTNs relative to HCs. Pulse pressure, arterial pressure, systolic/diastolic blood pressure, and hypertension duration were also correlated with patterns of rCBF change in the HTN group. Results-Relative to HCs, the HTN group shows greater rCBF decreases in prefrontal, anterior cingulate, and occipital areas over time, suggesting that these regions are more susceptible to hypertension-related dysfunction with advancing age. The HTN group also fails to show preservation of function over time in motor regions and in the temporal cortex and hippocampus as observed in HC. Although pulse pressure, mean arterial pressure, and systolic and diastolic pressure all correlate similarly with longitudinal rCBF changes, increased duration of hypertension is associated with decreased rCBF in prefrontal and anterior cingulate areas of functional vulnerability observed in the HTN group. Conclusions-These results show that hypertension significantly affects resting brain function in older individuals and suggest that duration of hypertension contributes significantly to the patterns of change over time.

Background-Statin use and serum cholesterol reduction have been proposed as preventions for dementia and mild cognitive impairment (MCI).

Disentangling the heterogeneity of brain aging in cognitively normal older adults is challenging, as multiple co-occurring pathologic processes result in diverse functional and structural changes. Capitalizing on machine learning methods applied to magnetic resonance imaging data from 400 participants aged 50 to 96 years in the Baltimore Longitudinal Study of Aging, we constructed normative cross-sectional brain aging trajectories of structural and functional changes. Deviations from typical trajectories identified individuals with resilient brain aging and multiple subtypes of advanced brain aging. We identified 5 distinct phenotypes of advanced brain aging. One group included individuals with relatively extensive structural and functional loss and high white matter hyperintensity burden. Another subgroup showed focal hippocampal atrophy and lower posterior-cingulate functional coherence, low white matter hyperintensity burden, and higher medial-temporal connectivity, potentially reflecting high brain tissue reserve counterbalancing brain loss that is consistent with early stages of Alzheimer's disease. Other subgroups displayed distinct patterns. These results indicate that brain changes should not be measured seeking a single signature of brain aging but rather via methods capturing heterogeneity and subtypes of brain aging. Our findings inform future studies aiming to better understand the neurobiological underpinnings of brain aging imaging patterns.

Background We examined the effect of the novel Alzheimer's disease (AD) risk variant rs11136000 single nucleotide polymorphism (SNP) in the clusterin gene (CLU) on longitudinal changes in resting state regional cerebral blood flow (rCBF) during normal aging and investigated its influence on cognitive decline in pre-symptomatic stages of disease progression. Methods Subjects were participants in the Baltimore Longitudinal Study of Aging. A subset of 88 cognitively normal older individuals had longitudinal 15O-water PET measurements of rCBF at baseline and up to 8 annual follow-up visits. We also analyzed trajectories of cognitive decline among CLU risk carriers and non-carriers both in individuals who remained cognitively normal (N=599) as well as in those who subsequently converted to mild cognitive impairment (MCI) or AD (N=95). Results Cognitively normal carriers of the CLU risk allele show significant and dose-dependent longitudinal increases in resting state rCBF in brain regions intrinsic to memory processes. There were no differences in trajectories of memory performance between CLU risk carriers and non-carriers who remained cognitively normal. However, in cognitively normal individuals who eventually convert to MCI or AD, CLU risk carriers show faster rates of decline in memory performance relative to non-carriers in the pre-symptomatic stages of disease progression. Conclusions The AD risk variant CLU influences longitudinal changes in brain function in asymptomatic individuals and is associated with faster cognitive decline in pre-symptomatic stages of disease progression. These results suggest mechanisms underlying the role of CLU in AD and may be important in monitoring disease progression in at-risk elderly.