Longitudinal Magnetic Resonance Imaging Studies of Older Adults: A Shrinking Brain

Abstract

Age-related loss of brain tissue has been inferred from cross-sectional neuroimaging studies, but direct measurements of gray and white matter changes from longitudinal studies are lacking. We quantified longitudinal magnetic resonance imaging (MRI) scans of 92 nondemented older adults (age 59-85 years at baseline) in the Baltimore Longitudinal Study of Aging to determine the rates and regional distribution of gray and white matter tissue loss in older adults. Using images from baseline, 2 year, and 4 year follow-up, we found significant age changes in gray (p < 0.001) and white (p < 0.001) volumes even in a subgroup of 24 very healthy elderly. Annual rates of tissue loss were 5.4 +/- 0.3, 2.4 +/- 0.4, and 3.1 +/- 0.4 cm3 per year for total brain, gray, and white volumes, respectively, and ventricles increased by 1.4 +/- 0.1 cm3 per year (3.7, 1.3, 2.4, and 1.2 cm3, respectively, in very healthy). Frontal and parietal, compared with temporal and occipital, lobar regions showed greater decline. Gray matter loss was most pronounced for orbital and inferior frontal, cingulate, insular, inferior parietal, and to a lesser extent mesial temporal regions, whereas white matter changes were widespread. In this first study of gray and white matter volume changes, we demonstrate significant longitudinal tissue loss for both gray and white matter even in very healthy older adults. These data provide essential information on the rate and regional pattern of age-associated changes against which pathology can be evaluated and suggest slower rates of brain atrophy in individuals who remain medically and cognitively healthy.

Sex hormones and brain volumes in a longitudinal study of middle‐aged men in the CARDIA study

“…However, volumes of other regions in the brain also show sex differences. Some imaging studies have reported age‐differences in the function of the parietal cortex and an increased sensitivity of the parietal lobe to the aging‐driven brain atrophy (Jacobs et al., 2011; Resnick, Pham, Kraut, Zonderman, & Davatzikos, 2003). Thus, parietal GM may be a brain region where the involvement of SHBG in both sex hormone and metabolic pathways converge in men.…”

Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

“…The Baltimore Longitudinal Study reported age-related changes in MRIderived signal intensity, which was believed to reflect demyelination and changes in water, protein, and mineral content in the old (Davatzikos and Resnick 2002). Results from the same study also reported that while WM volume was stable after 1 year in old subjects (Resnick et al 2000), it decreased regionally and globally after 4 years (Resnick et al 2003), suggestive that a critical age threshold was achieved. Functionally, longitudinal studies have shown WM atrophy in the CC of elderly men is associated with cognitive dysfunction (Sullivan et al 2002).…”

Individual patient diagnosis of AD and FTD via high-dimensional pattern classification of MRI

“…Voxel-based morphometry has also been used to evaluate voxel-by-voxel brain changes in healthy aging (Resnick, Pham et al 2003), AD (Ashburner, Csernansky et al 2003), and FTD (Rosen, Gorno-Tempini et al 2002;Grossman, McMillan et al 2004;Whitewell, Josephs et al 2005). These studies have confirmed patterns of atrophy that predominantly involve medial temporal lobe structures in subjects with mild cognitive impairment and patients with AD, and frontal and temporal regions in patients with FTD or AD, albeit the fronto-temporal atrophy in AD is part of a more widespread pattern of atrophy.…”

“…Structural MRI has the potential to both aid diagnosis and provide objective surrogate markers of effects of pharmacological interventions designed to slow or halt the neurodegenerative process. Advanced image analysis methodologies have also been described in the literature, aiming to quantify structural characteristics of healthy individuals and patients with AD or FTD (Thompson, Mega et al 2001;Resnick, Pham et al 2003;Fox and Schott 2004;Grossman, McMillan et al 2004;Chang, Lomen-Hoerth et al 2005;Likeman, Anderson et al 2005;Short, Broderick et al 2005;Barnes, Whitwell et al 2006).…”