James D. Acker

Aging, sexual dimorphism, and hemispheric asymmetry of the cerebral cortex: replicability of regional differences in volume.

We examined age-, sex-, and hemisphere-related differences in the cerebral cortex. Volumes of the cerebral hemispheres and 13 regions of interest (ROIs) were measured on magnetic resonance images of 200 healthy adults. The strength of association between age and volume differed across ROIs. The lateral prefrontal cortex exhibited the greatest age-related differences, whereas significantly weaker associations were observed in the prefrontal white matter, sensory-motor, and visual association regions. The hippocampal shrinkage was significant in people in their mid-fifties. The primary visual, anterior cingulate, the inferior parietal cortices, and the parietal white matter showed no age-related differences. The pattern of age-related regional differences replicated the findings previously obtained on an independent sample drawn from the same population. Men evidenced larger volumes in all ROIs except the inferior parietal lobule, even after sexual dimorphism in body size was statistically controlled. In some regions (hippocampus and fusiform gyrus) men exhibited steeper negative age-related trends than women. Although a typical pattern of global hemispheric asymmetry was observed, the direction and magnitude of regional volumetric asymmetry was as inconsistent as in the previous reports. Thus, a pattern of age-related shrinkage suggesting increased vulnerability of the lateral prefrontal cortex to aging appears stable and replicable, whereas little consistency exists in sex-related and hemispheric differences in regional cortical volumes.

Neuroanatomical correlates of cognitive aging: Evidence from structural magnetic resonance imaging.

To examine putative brain substrates of cognitive functions differentially affected by age the authors measured the volume of cortical regions and performance on tests of executive functions, working memory, explicit memory, and priming in healthy adults (18-77 years old). The results indicate that shrinkage of the prefrontal cortex mediates age-related increases in perseveration. The volume of visual processing areas predicted performance on nonverbal working memory tasks. Contrary to the hypotheses, in the examined age range, the volume of limbic structures was unrelated to any of the cognitive functions; verbal working memory, verbal explicit memory, and verbal priming were independent of cortical volumes. Nevertheless, among the participants aged above 60, reduction in the volume of limbic structures predicted declines in explicit memory. Chronological age adversely influenced all cognitive indices, although its effects on priming were only indirect, mediated by declines in verbal working memory.

Differential aging of the medial temporal lobe A study of a five-year change

Objective: To test the hypothesis that entorhinal cortex (EC) volume decreases at a slower rate than the hippocampal (HC) volume in healthy adults, and to examine whether the rate of shrinkage increases with age. Methods: Volumes of the HC and EC were measured twice on MRI scans of 54 healthy adults (aged 26 to 82 years), with an average interval of 5 years. Results: Markedly different age trends were noted in the examined regions. The EC showed no age-related differences on both occasions and only minimal age-related change (0.33%/y). By contrast, the HC exhibited significant age-related differences at baseline and at follow-up evaluation and decreased at a faster pace of 0.86%/y. Older participants (aged ≥50 years) showed increased annual shrinkage of the HC (1.18%) and EC shrinkage (0.53%/y). The rate of HC volume loss significantly exceeded that of the EC. No EC shrinkage and modest HC volume reduction were observed in people aged <50 years. Conclusions: Age-related shrinkage occurs in the medial temporal lobes of healthy adults, with significant hippocampal decline and minimal entorhinal changes. In both regions, the rate of decline accelerates with age, although the role of pathologic factors in age-related increase of volume loss merits further investigation.

Hypertension and the brain: vulnerability of the prefrontal regions and executive functions.

Untreated hypertension negatively affects brain anatomy and cognitive functions, but the effects of medically treated hypertension are unclear. The authors compared 40 middle-age and older adults diagnosed with essential hypertension to demographically matched normotensive peers. Volumes of 7 brain regions and deep and periventricular white-matter hyperintensities (WMH) were measured on magnetic resonance imaging scans. Performance in 4 cognitive domains (perseveration, working memory, fluid reasoning, and vocabulary knowledge) was evaluated. Persons with hypertension had smaller prefrontal cortex and underlying white matter volumes and increased frontal WMH. No group differences were found in other examined brain regions. Among examined cognitive variables, hypertensive patients committed significantly more perseverative errors. Thus, even controlled hypertension may be associated with deficits in brain structure and cognition, warranting further study.

Selective neuroanatornic abnormalities in Down's syndrome and their cognitive correlates Evidence from MRI morphometry

Article abstract—We examined the pattern of neuroanatomic abnormalities in adults with Downs syndrome (DS) and the cognitive correlates of these abnormalities. Specifically, we compared this pattern with what would be predicted by the hypotheses attributing DS pathology to either premature aging or Alzheimers disease. We measured a number of brain regions on MRIs of 25 subjects: 13 persons with the DS phenotype and 12 age- and sex-matched healthy volunteers. Study participants had no history of cardiovascular disease, diabetes, thyroid dysfunction, or seizure disorder. After statistical adjustment for differences in body size, we found that, in comparison with controls, DS subjects had substantially smaller cerebral and cerebellar hemispheres, ventral pons, mammillary bodies, and hip-pocampal formations. In the cerebellar vermis of DS subjects, we observed smaller lobules VI to VIII without appreciable differences in other regions. In addition, we noted trends for shrinkage of the dorsolateral prefrontal cortex, anterior cingulate gyrus, inferior temporal and parietal cortices, parietal white matter, and pericalcarine cortex in DS subjects compared with normal controls. The parahippocampal gyrus was larger in DS subjects. We found no significant group differences in the volumes of the prefiontal white matter, the orbitofiontal cortex, the pre- and postcentral gyri, or the basal ganglia. We conclude that the pattern of selective cerebral damage in DS does not clearly fit the predictions of the premature aging or Alzheimers disease hypotheses. To examine the relationship between brain abnormalities and cognitive deficits observed in DS, we correlated the size of brain regions that were significantly reduced in DS with performance on tests of intelligence and language. The correlational analysis suggested age-related decline in the DS subjects in general intelligence and basic linguistic skills. General intelligence and mastery of linguistic concepts correlated negatively with the volume of the parahippocampal gyrus. There was no relationship between total brain size and the cognitive variables.

Vascular health and longitudinal changes in brain and cognition in middle-aged and older adults.

The impact of vascular health on the relations between structural brain changes and cognition was assessed in a longitudinal study of 46 adults, 23 of whom remained healthy for 5 years and 23 of whom had hypertension at baseline or acquired vascular problems during follow-up. At both measurement occasions, the volume of white matter hyperintensities (WMH) and regional brain volumes correlated with age. In 5 years, WMH volume more than doubled in the vascular risk group but did not increase in healthy participants. The frontal lobes had the highest WMH load at baseline and follow-up; the parietal WMH showed the greatest rate of expansion. In the vascular risk group, systolic blood pressure at follow-up correlated with posterior WMH volume. The fastest cortical shrinkage was observed in the prefrontal cortex and the hippocampus. Fluid intelligence correlated with WMH burden and declined along with faster WMH progression. In the vascular risk group, WMH progression and shrinkage of the fusiform cortex correlated with decline in working memory. Thus, poor vascular health contributes to age-related declines in brain and cognition, and some of the age-related declines may be limited to persons with elevated vascular risk.

Age-related differences in regional brain volumes: A comparison of optimized voxel-based morphometry to manual volumetry

Regional manual volumetry is the gold standard of in vivo neuroanatomy, but is labor-intensive, can be imperfectly reliable, and allows for measuring limited number of regions. Voxel-based morphometry (VBM) has perfect repeatability and assesses local structure across the whole brain. However, its anatomic validity is unclear, and with its increasing popularity, a systematic comparison of VBM to manual volumetry is necessary. The few existing comparison studies are limited by small samples, qualitative comparisons, and limited selection and modest reliability of manual measures. Our goal was to overcome those limitations by quantitatively comparing optimized VBM findings with highly reliable multiple regional measures in a large sample (N=200) across a wide agespan (18-81). We report a complex pattern of similarities and differences. Peak values of VBM volume estimates (modulated density) produced stronger age differences and a different spatial distribution from manual measures. However, when we aggregated VBM-derived information across voxels contained in specific anatomically defined regions (masks), the patterns of age differences became more similar, although important discrepancies emerged. Notably, VBM revealed stronger age differences in the regions bordering CSF and white matter areas prone to leukoaraiosis, and VBM was more likely to report nonlinearities in age-volume relationships. In the white matter regions, manual measures showed stronger negative associations with age than the corresponding VBM-based masks. We conclude that VBM provides realistic estimates of age differences in the regional gray matter only when applied to anatomically defined regions, but overestimates effects when individual peaks are interpreted. It may be beneficial to use VBM as a first-pass strategy, followed by manual measurement of anatomically defined regions.

Neuroanatomical and cognitive correlates of adult age differences in acquisition of a perceptual-motor skill

The objective of this study was to examine age differences in procedural learning and performance in conjunction with differential aging of central nervous system (CNS) structures. Sixty‐eight healthy volunteers (age 22–80) performed a pursuit rotor task (four blocks of 20 15‐second trials each). Volumes of the cerebellar hemispheres, neostriatum, prefrontal cortex, and hippocampus were measured from Magnetic Resonance (MR) images. Improvement in pursuit rotor performance was indexed by increase in time on target (TOT). A general improvement trend was evident across the blocks of trials. Overall, younger participants showed significantly longer TOT. The rate of improvement was age‐invariant during the initial stages of skill acquisition but became greater in middle‐aged participants as the practice progressed. When the influences of regional brain volumes were taken into account, the direct age effect on mean TOT measured during the first day of practice disappeared. Instead, reduced volumes of the cerebellar hemispheres and the putamen and poorer performance on nonverbal working memory tasks predicted shorter TOT. In contrast, neither the volume of the caudate and the hippocampus, nor verbal working memory showed association with motor performance. Pursuit rotor performance at the later stages of practice was unrelated to the reduction in putamen volume and was affected directly by age, cerebellar volume, and nonverbal working memory proficiency. We conclude that in a healthy population showing no clinical signs of extrapyramidal disease, age‐related declines in procedural learning are associated with reduced volume of the cerebellar hemispheres and lower nonverbal working memory scores. During initial stages of skill acquisition, reduced volume of the putamen is also predictive of poorer performance. Microsc. Res. Tech. 51:85–93, 2000.

Age-related differences in the course of cognitive skill acquisition: the role of regional cortical shrinkage and cognitive resources.

This study examined the impact of age-related differences in regional cerebral volumes and cognitive resources on acquisition of a cognitive skill. Volumes of brain regions were measured on magnetic resonance images of healthy adults (aged 22-80). At the early stage of learning to solve the Tower of Hanoi puzzle, speed and efficiency were associated with age, prefrontal cortex volume, and working memory. A similar pattern of brain-behavior associations was observed with perseveration measured on the Wisconsin Card Sorting Test. None of the examined structural brain variables were important at the later stages of skill acquisition. When hypertensive participants were excluded, the effect of prefrontal shrinkage on executive aspects of performance was no longer significant, but the effect of working memory remained.

Age-related deficits in generation and manipulation of mental images: II. The role of dorsolateral prefrontal cortex

The authors investigated neural substrates of age-related declines in mental imagery. Healthy adult participants (ages 19 to 77) performed a series of visual-spatial mental imagery tasks that varied in apparent difficulty and involved stimuli of varying graphic complexity. The volumes of the dorsolateral frontal cortex (DLPFC) and posterior visual processing areas were estimated from magnetic resonance imaging scans. The volume of the DLPFC and the fusiform cortex, working-memory capacity, and performance on the tasks involving image generation and manipulation were significantly reduced with age. Further analyses suggested that age-related deficits in performance on mental imagery tasks may stem in part from age-related shrinkage of the prefrontal cortex and age-related declines in working memory but not from age-related slowing of sensorimotor reaction time. The volume of cortical regions associated with modality-specific visual information processing did not show a consistent relationship with specific mental imagery processes.