Volume In Older Adults Research Articles

Elevated brain lesion volumes in older adults who use calcium supplements: a cross-sectional clinical observational study

Elevated brain lesion volumes in older adults who use calcium supplements: a cross-sectional clinical observational study

Heritability of brain volumes in older adults: the Older Australian Twins Study

The relative contributions of genetic and environmental factors to brain structure change throughout the lifespan. Brain structures have been reported to be highly heritable in middle-aged individuals and younger; however, the influence of genes on brain structure is less studied in older adults. We performed a magnetic resonance imaging study of 236 older twins, with a mean age of 71.4 ± 5.7 years, to examine the heritability of 53 brain global and lobar volumetric measures. Total brain volume (63%) and other volumetric measures were moderately to highly heritable in late life, and these genetic influences tended to decrease with age, suggesting a greater influence of environmental factors as age advanced. Genetic influences were higher in men and on the left hemisphere compared with the right. In multivariate models, common genetic factors were observed for global and lobar total and gray matter volumes. This study examined the genetic contribution to 53 brain global and lobar volumetric measures in older twins for the first time, and the influence of age, sex, and laterality on these genetic contributions, which are useful information for a better understanding of the process of brain aging and helping individuals to have a healthy aging.

Depressive Symptoms, Symptom Dimensions, and White Matter Lesion Volume in Older Adults: A Longitudinal Study

White matter lesions (WMLs) are associated with depressive symptoms in older adults. However, it is not clear whether different symptom dimensions of depression have distinct associations with WMLs. The authors assessed the longitudinal relationships of the Center for Epidemiologic Studies Depression Scale (CES-D) total score and subscale scores with WML volume in the Baltimore Longitudinal Study of Aging. Using a prospective observational design, the authors examined WML volume and depressive symptoms at 1- to 2-year intervals for up to 9 years in 116 dementia-free participants (mean age: 68.78 ± 7.68). At each visit, depressive symptoms were measured with the CES-D and WML volumes were quantified from structural magnetic resonance imaging scans. Higher CES-D full-scale scores were associated with greater WML volume and with a faster rate of volume increases over time in women, especially at older ages. Higher depressed mood and somatic symptoms subscale scores were associated with greater increases in WML volume over time at older ages. In men, depressed mood and somatic symptoms were associated with larger WML volume at baseline. Findings confirm an association between WMLs and depressive symptoms and suggest that depressed mood and somatic symptoms may be stronger predictors of depression-related brain changes than lack of well-being. Age and sex may moderate the relationships between depressive symptoms and WMLs. Understanding particular symptom dimensions of depressive symptoms has implications for treatment and may lead to targeted interventions and more precise knowledge of mechanisms underlying depression.

Six-Minute Walking Distance Correlated with Memory and Brain Volume in Older Adults with Mild Cognitive Impairment: A Voxel-Based Morphometry Study

Background/Aims: High fitness levels play an important role in maintaining memory function and delaying the progression of structural brain changes in older people at risk of developing dementia. However, it is unclear which specific regions of the brain volume are associated with exercise capacity. We investigated whether exercise capacity, determined by a 6-min walking distance (6MWD), is associated with measures of logical and visual memory and where gray matter regions correlate with exercise capacity in older adults with mild cognitive impairment (MCI). Methods: Ninety-one community-dwelling older adults with MCI completed a 6-min walking test, structural magnetic resonance imaging scanning, and memory tests. The Wechsler Memory Scale-Revised Logical Memory and Rey-Osterrieth Complex Figure Tests were used to assess logical and visual memory, respectively. Results: The logical and visual memory tests were positively correlated with the 6MWD (p < 0.01). Poor performance in the 6MWD was correlated with a reduced cerebral gray matter volume in the left middle temporal gyrus, middle occipital gyrus, and hippocampus in older adults with MCI. Conclusions: These results suggest that a better 6MWD performance may be related to better memory function and the maintenance of gray matter volume in older adults with MCI.

Serum Ionized Calcium May Be Related to White Matter Lesion Volumes in Older Adults: A Pilot Study

White matter lesions have detrimental effects upon older adults, while serum calcium levels have been associated with elevated vascular risk and may be associated with these lesions. Depression, a serious mental disorder characterized by disturbances in calcium metabolism, may be an important contributor to any calcium-lesion relationship. This cross-sectional pilot study examined the association between serum ionized calcium (the physiologically active form of calcium) and white matter lesion volumes in a sample of depressed and non-depressed older adults (N = 42; 60 years and older). Serum ionized calcium was determined using an ion-selective electrode technique, while lesion volumes were estimated from magnetic resonance imaging using an automated expectation-maximization segmentation. A linear regression model, controlling for age and group (depression vs. comparison), showed a trend for a positive relationship between serum ionized calcium and white matter lesion volume (β = 4.34, SE = 2.27, t = 1.91, p = 0.063). Subsample analyses with depressed participants showed a significant positive relationship between higher ionic calcium and greater lesion volume (β = 6.41, SE = 2.53, t = 2.53, p = 0.018), but no association was found for non-depressed participants. Sex-specific subsample analyses showed a significant positive relationship between higher calcium and greater lesion volume in men only (β = 7.49, SE = 3.42, t = 2.19, p = 0.041). These preliminary results indicate that serum ionized calcium may be associated with white matter lesions in older adults, particularly among men and individuals with depression. Larger studies are needed to confirm these findings.

Negative life stress and longitudinal hippocampal volume changes in older adults with and without depression

Major depressive disorder is associated with smaller hippocampal volumes but the mechanisms underlying this relationship are unclear. To examine the effect of environmental influences, we examined the relationship between self-reported stressors and two-year change in hippocampal volume. Seventy elderly nondepressed subjects and eighty-nine elderly depressed subjects were followed for two years. The number of negative stressful life events (nSLE), perceived stress levels, and cranial MRI were obtained at baseline and at the two-year assessment. For secondary analyses, subjects provided blood for 5-HTTLPR polymorphism genotyping. After controlling for covariates including presence or absence of depression, greater numbers of baseline nSLEs were significantly associated with greater baseline hippocampal volumes bilaterally. Greater numbers of baseline nSLEs were also associated with reduction in hippocampal volume over two years in the right but not the left hemisphere. Neither perceived stress levels nor changes in stress measures were significantly associated with hippocampal volume measures. However, in secondary analyses, we found that increases in perceived stress over time was associated with volume reduction of the left hippocampus, but only in 5-HTTLPR L/L homozygotes. Our findings suggest different short- and long-term effects of negative life stressors on hippocampal volumes in older adults. These effects appear independent on the presence or absence of depression. Furthermore, these effects may be moderated by genetic polymorphisms in key neurotransmitter systems. These novel findings have important implications for understanding environmental influences on brain aging.

Serum Ionized Calcium May Be Related to White Matter Lesion Volumes in Older Adults: A Pilot Study

Serum Ionized Calcium May Be Related to White Matter Lesion Volumes in Older Adults: A Pilot Study

Vitamin D concentration and lateral cerebral ventricle volume in older adults

Vitamin D deficiency is associated with an enlargement of the lateral cerebral ventricles in rodents. The effect of low serum 25-hydroxyvitamin D (25OHD) on lateral cerebral ventricle volume has not been studied yet in humans. The purpose of this cross-sectional study was to determine whether vitamin D deficiency was associated with greater lateral cerebral ventricle volume in older adults. Ninety-two Caucasian community-dwellers with no clinical hydrocephalus (mean, 72.2 ± 6.2 years; 46.7% female) were divided into two groups according to serum 25OHD concentration (deficiency ≤ 50 nmol/L; normal > 50 nmol/L). Cerebral ventricular volume was quantified using semi-automated software from three-dimensional T1-weighted MRI. Age, gender, body mass index, blood pressure, education level, Mini-Mental State Examination, white matter lesions, and serum calcium concentrations were used as covariates. There was an inverse linear association between 25OHD concentration and ventricular volume (p = 0.049). Compared to individuals with normal 25OHD, those with 25OHD deficiency (n = 33) had 28% larger lateral ventricles (46.9 ± 26.8 mL versus 36.6 ± 16.4 mL, p = 0.026). Vitamin D deficiency was associated with an increase in ventricular volume (adjustedβ = 16.55, p = 0.023). The ventricular enlargement involved ventricle bodies (p = 0.025) but not temporal horns (p = 0.112). Serum 25OHD deficiency was associated with larger lateral cerebral ventricles. These findings provide a scientific base for vitamin D replacement trials.

Activity Preserves Brain Volume in Older Adults

Activity Preserves Brain Volume in Older Adults

The Relationship Between Brain Volume and Walking Outcomes in Older Adults With and Without Diabetic Peripheral Neuropathy

OBJECTIVEDiabetic peripheral neuropathy (DPN) alters walking. Yet, the compensatory role of central locomotor circuits remains unclear. We hypothesized that walking outcomes would be more closely related to regional gray matter volumes in older adults with DPN as compared with nonneuropathic diabetic patients and nondiabetic control subjects.RESEARCH DESIGN AND METHODSClinically important outcomes of walking (i.e., speed, stride duration variability, and double support time) were measured in 29 patients with DPN (type 2 diabetes with foot-sole somatosensory impairment), 68 diabetic (DM) patients (type 2 diabetes with intact foot-sole sensation), and 89 control subjects. Global and regional gray matter volumes were calculated from 3 Tesla magnetic resonance imaging.RESULTSDPN subjects walked more slowly (P = 0.005) with greater stride duration variability (P < 0.001) and longer double support (P < 0.001) as compared with DM and control subjects. Diabetes was associated with less cerebellar gray matter volume (P < 0.001), but global gray matter volume was similar between groups. DPN subjects with lower gray matter volume globally (P < 0.004) and regionally (i.e., cerebellum, right-hemisphere dorsolateral prefrontal cortex, basal ganglia, P < 0.005) walked more slowly with greater stride duration variability and/or longer double support. Each relationship was stronger in DPN than DM subjects. In control subjects, brain volumes did not relate to walking patterns.CONCLUSIONSStrong relationships between brain volumes and walking outcomes were observed in the DPN group and to a lesser extent the DM group, but not in control subjects. Individuals with DPN may be more dependent upon supraspinal elements of the motor control system to regulate several walking outcomes linked to poor health in elderly adults.

Cognitive and Neural Correlates of Aerobic Fitness in Obese Older Adults

Background/Study Context: Aerobic fitness is associated with preserved cognition and brain volume in older adulthood. The current study investigated whether the benefits of aerobic fitness extend to obese older adults, a segment of the population that is rapidly growing and who exhibit compromised cognition and brain structure relative to their nonobese counterparts. Methods: Measures of obesity, aerobic fitness, cognition (processing speed, executive function, spatial ability, memory), and regional brain volumes (prefrontal gray, prefrontal white, hippocampus) were obtained from 19 obese older adults aged 65 to 75. Hierarchical linear regression analyses were conducted to examine the proportion of unique variance in cognitive and volumetric measures accounted for by aerobic fitness after controlling for covariates (age, gender, and waist circumference). Results: Aerobic fitness accounted for a significant amount of unique variance in processing speed (adjusted R 2 = .44), executive function (adjusted R 2 = .34), and hippocampal volume (adjusted R 2 = .27). Conclusion: This novel pattern of results suggests that obesity does not preclude the benefits of fitness for cognition and brain volume in older adults. Fitness appears to be a beneficial factor for maintenance of processing speed, executive function, and hippocampal volume, which are vulnerable to age- and/or obesity-related decline.

The Association Between Decline in Physical Functioning and Atrophy of Medial Temporal Areas in Community-Dwelling Older Adults With Amnestic and Nonamnestic Mild Cognitive Impairment

Makizako H, Shimada H, Doi T, Yoshida D, Ito K, Kato T, Shimokata H, Washimi Y, Endo H, Suzuki T. The association between decline in physical functioning and atrophy of medial temporal areas in community-dwelling older adults with amnestic and nonamnestic mild cognitive impairment. Objective To examine whether declining performance in aspects of physical functioning, including lower extremity muscle strength, 1-legged balance, walking speed, and exercise capacity, is associated with atrophy of medial temporal areas in community-dwelling older adults with mild cognitive impairment (MCI). Design Cross-sectional study. Setting General community in Japan. Participants Community-dwelling older adults 65 years and older with a Clinical Dementia Rating of 0.5 or memory complaints were enrolled in this study. This study examined 34 participants with amnestic MCI (aMCI) and 58 nonamnestic MCI (non-aMCI) participants. Interventions Not applicable. Main Outcome Measures The following physical performance tests were conducted: muscle strength of knee extension, 1-legged standing time, 5-m walking test, and 6-minute walk test (6MWT). The z scores of the voxel-based specific regional analysis system for Alzheimer's disease were determined to assess the degree of atrophy in the bilateral medial temporal areas including the entorhinal cortex (MTA-ERC). Results In the aMCI group, 6MWT performance was associated with MTA-ERC atrophy ( β=–.462, P=.014) after controlling for age. In the stepwise multiple regression analyses, 6MWT and body mass index were found to be significant determinants of MTA-ERC atrophy in all participants ( R 2=.275), as well as the aMCI and non-aMCI groups when analyzed separately ( R 2=.418 and R 2=.216, respectively). Conclusions A decline in exercise capacity was found to be more closely associated with atrophy of the MTA-ERC compared with other aspects of physical functioning in older adults with MCI, especially the amnestic type. These findings suggest that it is important for future studies to investigate the effects of increased aerobic activity and improved fitness on brain volume in older adults at risk of developing dementia.

C-reactive protein is related to memory and medial temporal brain volume in older adults

Recent research suggests a central role for inflammatory mechanisms in cognitive decline that may occur prior to evidence of neurodegeneration. Limited information exists, however, regarding the relationship between low-grade inflammation and cognitive function in healthy older adults. This study examined the relation between inflammation, verbal memory consolidation, and medial temporal lobe volumes in a cohort of older community-dwelling subjects. Subjects included 141 functionally intact, community-dwelling older adults with detectable (n=76) and undetectable (n=65) levels of C-reactive protein. A verbal episodic memory measure was administered to all subjects, and measures of delayed recall and recognition memory were assessed. A semiautomated parcellation program was used to analyze structural MRI scans. On the episodic memory task, analysis of covariance revealed a significant CRP group by memory recall interaction, such that participants with detectable levels of CRP evidenced worse performance after a delay compared to those with undetectable levels of CRP. Individuals with detectable CRP also demonstrated lower performance on a measure of recognition memory. Imaging data demonstrated smaller left medial temporal lobe volumes in the detectable CRP group as compared with the undetectable CRP group. These findings underscore a potential role for inflammation in cognitive aging as a modifiable risk factor.

Entorhinal cortex volume in older adults: Reliability and validity considerations for three published measurement protocols

Measuring the entorhinal cortex (ERC) is challenging due to lateral border discrimination from the perirhinal cortex. From a sample of 39 nondemented older adults who completed volumetric image scans and verbal memory indices, we examined reliability and validity concerns for three ERC protocols with different lateral boundary guidelines (i.e., Goncharova, Dickerson, Stoub, & deToledo-Morrell, 2001; Honeycutt et al., 1998; Insausti et al., 1998). We used three novice raters to assess inter-rater reliability on a subset of scans (216 total ERCs), with the entire dataset measured by one rater with strong intra-rater reliability on each technique (234 total ERCs). We found moderate to strong inter-rater reliability for two techniques with consistent ERC lateral boundary endpoints (Goncharova, Honeycutt), with negligible to moderate reliability for the technique requiring consideration of collateral sulcal depth (Insausti). Left ERC and story memory associations were moderate and positive for two techniques designed to exclude the perirhinal cortex (Insausti, Goncharova), with the Insausti technique continuing to explain 10% of memory score variance after additionally controlling for depression symptom severity. Right ERC-story memory associations were nonexistent after excluding an outlier. Researchers are encouraged to consider challenges of rater training for ERC techniques and how lateral boundary endpoints may impact structure-function associations.

Gray and white matter brain volumes in older adults with bipolar disorder

Structural magnetic resonance imaging (MRI) studies have been inconsistent in demonstrating volumetric differences in subjects with bipolar disorder. Most studies have not found difference in total gray or white matter in bipolar patients compared with controls, but there have been several studies suggesting that regional abnormalities are present. These have predominately been located in the frontal and temporal lobes. Since age has been inversely correlated with total gray matter in patients, analyses of gray matter changes in older adults or in studies that have included older subjects have been difficult. This study assessed the presence of gray matter volume, and the potential for regional volumetric differences in older adults with bipolar disorder. Fifty-six older adults with DSM-IV bipolar disorder (mean age 60.5) and 43 non-psychiatrically ill controls (mean age 58.1) had structured interviews and MRI scanning on a 1.5T GE Scanner. Image parcellation divided the cerebrum into 16 units. Volumetric differences were examined using the multivariate linear regression models with alpha = 0.05. Relative to controls, the older adults with bipolar disorder had significantly smaller gray matter volumes bilaterally in the inferior frontal areas. White matter volume was also reduced in these same areas but did not reach statistical significance when controlled for gender and age. No significant difference was noted in total gray or white matter volumes. Older adults with bipolar disorder showed gray matter volumetric deficits in inferior frontal lobe regions which include structures identified as contributing to the anterior limbic network.

The relation of worry to prefrontal cortex volume in older adults with and without generalized anxiety disorder

Despite the widespread prevalence of generalized anxiety disorder (GAD) in later life, almost nothing is known about the neural aspects of worry in adults over the age of 60. Given the ongoing rapid increase in the older adult population, the relatively poor response rates to current interventions for late life GAD, and the effects of age-related changes to the brain, additional research on worry neurobiology is needed. The study group comprised 15 older GAD patients and 15 matched controls who were compared on clinical measures and brain volumes. It was expected that prefrontal cortex (PFC) volumes [medial orbital cortex (mOFC), dorsolateral cortex (DLPFC)] would show positive relations to worry scores, and weaker relations to more general measures of anxiety and depression. Negative relations were expected between amygdala volumes and worry scores. As expected, mOFC volumes were positively related to worry scores; however, DLPFC and amygdala volumes were not. The mOFC is involved in emotional decision-making under uncertain conditions and has the ability to suppress the amygdala, both of which are hypothesized functions of worry. Results are partly consistent with GAD theory and suggest that worry may involve neural areas that are also involved in the successful control of anxiety.

Posterior Cingulate and Lateral Parietal Gray Matter Volume in Older Adults with Depressive Symptoms

Depressive symptoms occurring late in life are an important risk factor for Alzheimer’s disease (AD). The latest research finds that onset of depressive symptoms in late life may herald the development of AD, not only for amnestic Mild Cognitive Impairment (aMCI) patients, but also for cognitively-normal older adults. Neuroimaging of brain structure, blood flow, and glucose metabolism indicates that depressive symptoms in late life are accompanied by structural and functional changes in limbic brain regions vulnerable to AD. The present cross-sectional study was guided by the hypothesis that compared to their non-depressed counterparts, older adults with mild to moderate depressive symptoms have less volume in limbic structures vulnerable to changes in AD—specifically, cortical midline structures such as anterior cingulate and posterior cingulate cortex as well as mesial temporal regions such as bilateral hippocampi and amygdalae. Consistent with our hypothesis, results of a voxel-based morphometry analysis revealed smaller retrosplenial, posterior cingulate, and precuneus gray matter volumes in depressed individuals relative to healthy controls. Right lateral parietal cortex—another region vulnerable to change in AD—was also smaller in the group with depressive symptoms. Contrary to our hypothesis, no volumetric differences were found in the anterior cingulate cortex or mesial temporal lobe. Results of this study show a relationship between geriatric depressive symptoms and brain volume in regions vulnerable to AD. Follow-up of participants over time will tell if brain changes detected here predict development of AD.

Hippocampal volume is as variable in young as in older adults: Implications for the notion of hippocampal atrophy in humans

Previous studies in humans have shown the presence of an age-related reduction of hippocampal (HC) volume, as well as the presence of reduced HC volume in psychiatric populations suffering from schizophrenia, depression or post-traumatic stress disorder. Altogether, these data suggested that aging or psychiatric disease can have neurotoxic effects on the hippocampus, and lead to HC atrophy. However, these two sets of findings imply that HC volume in young healthy adults should present less variability than HC volume in older adults and psychiatric populations. In the present study, we assessed HC volume in 177 healthy men and women aged from 18 to 85 years of age. We show that the dispersion around the mean of HC volume is not different in young and older adults, so that 25% of young healthy adults present HC volume as small as the average participants aged 60 to 75 years. This shows that HC volume is as variable in young as in older adults and suggests that smaller HC volume attributed to the aging process in previous studies could in fact represent HC volume determined early in life. We also report that within similar age groups, the percentage of difference in HC volume between the individuals with the smallest HC volume (smallest quartile) and the group average is greater than the percentage of difference reported to exist between psychiatric populations and normal control in recent meta-analyses. Taken together, these results confront the notion of hippocampal atrophy in humans and raise the possibility that pre-determined inter-individual differences in HC volume in humans may determine the vulnerability for age-related cognitive impairments or psychopathology throughout the lifetime.

Resistance training volume in older adults: effect of a short-term program on muscle strength

Resistance training volume in older adults: effect of a short-term program on muscle strength

One-year age changes in MRI brain volumes in older adults.

Longitudinal studies indicate that declines in cognition and memory accelerate after age 70 years. The neuroanatomic and neurophysiologic underpinnings of cognitive change are unclear, as there is little information on longitudinal brain changes. We are conducting a longitudinal neuroimaging study of nondemented older participants in the Baltimore Longitudinal Study of Aging. This report focuses on age and sex differences in brain structure measured by magnetic resonance imaging during the first two annual evaluations. Cross-sectional results from 116 participants aged 59-85 years reveal significantly larger ventricular volumes and smaller gray and white matter volumes in older compared with younger participants and in men compared with women. Regional brain volumes show that the effects of age and sex are not uniform across brain regions. Age differences are greatest for the parietal region. Sex differences tend to be larger for frontal and temporal than parietal and occipital regions. Longitudinal analysis demonstrates an increase of 1526 mm(3) in ventricular volume over 1 year, but no detectable change in total or regional brain volumes. Definition of the pattern and rate of longitudinal brain changes will facilitate the detection of pathological brain changes, which may be predictors of dementia.