Melissa Lamar

Subjective Cognitive Complaints and Longitudinal Changes in Memory and Brain Function

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.

Quantitative Tract-Specific Measures of Uncinate and Cingulum in Major Depression Using Diffusion Tensor Imaging

Previous findings suggested the role of the prefrontal cortex, hippocampus, and cingulate gyrus in major depressive disorders (MDD), but the white matter microstructural abnormalities of the fibers connecting these brain structures are not known. The purpose of this study was to test the hypothesis that white matter abnormalities are present in association fibers of the uncinate fasciculus (UF) and cingulum bundle (CB) among MDD subjects. A total of 21 MDD subjects aged between 30 and 65 years and 21 age-matched healthy controls (HC) were recruited. All subjects were right-handed and without history of diabetes or other cardiac diseases. We extracted quantitative tract-specific measures based on diffusion tensor imaging tractography to examine both diffusivity and geometric properties of the UF and CB. Significantly decreased fractional anisotropy (FA) and increased radial diffusivity of the right UF were observed in MDD patients compared with HC (p<0.05), while their geometric characteristics remained relatively unchanged. Among MDD subjects, depression severity had a significant negative correlation with normalized number of fibers (NNF) in the right UF (r=−0.53, p=0.02). We also found significant age effect (old<young) in HC group and laterality effect (L>R) in both groups in the FA measure of the CB. Our study demonstrates novel findings of white matter microstructural abnormalities of the right UF in MDD. In the MDD group, the severity of depression is associated with reduced NNF in the right UF. These findings have implications for both clinical manifestations of depression as well as its pathophysiology.

Longitudinal changes in verbal memory in older adults: Distinguishing the effects of age from repeat testing

Objective: To characterize the relationship between age-related memory change and repeat testing using serial administrations of the California Verbal Learning Test (CVLT) in 385 nondemented Baltimore Longitudinal Study of Aging participants aged 55 and older with two or more memory assessments. Methods: The authors investigated longitudinal change and the effects of age, sex, education, and repeat testing on new learning and recall by analyzing measures of learning and interference, short- and long-delay free and cued recall, and recognition hits in separate mixed-effects regressions. Results: The authors found cross-sectional effects of age (p ≤ 0.001) and sex (p ≤ 0.05) on learning and interference, regardless of baseline performance. Younger adults outperformed older adults, and women outperformed men. Longitudinal age changes were documented across total learning and long-delay free and cued recall regardless of baseline scores (p ≤ 0.05). In addition, controlling for baseline scores enhanced the sensitivity for detection of longitudinal age changes on Trial 5, short-delay cued recall and recognition hits (p ≤ 0.05). The influence of repeated administrations changed with advancing baseline age for total learning and short- and long-delay recall such that younger baseline age was associated with improvement over time whereas older baseline age was associated with decline over time. Conclusion: Longitudinal declines in CVLT performance exist in normal aging and are influenced by baseline age. Furthermore, failure to account for the influence of repeat testing with aging may decrease sensitivity to detect pathologic decline.

Capacity to maintain mental set in dementia.

Two experiments investigating the capacity to sustain mental set in dementia were conducted. Experiment 1 analyzed performance of a non-demented control group (NC), participants with Alzheimers disease (AD) and participants with ischemic vascular dementia (IVD) on the Boston Revision of the Wechsler Memory Scale Mental Control subtest (MC). On simple tasks there were no between-group differences after controlling for time to completion. On complex tasks, NC participants outperformed both dementia groups and AD participants obtained higher accuracy indices than IVD participants. The IVD group produced a disproportionate number of commission errors regardless of task complexity. The AD group tended to produce more omission errors on more difficult measures of mental set. Individual task performance was divided into three sections-first, middle, and last. IVD participants made fewer and fewer correct responses over all three sections, whereas performance of AD participants leveled off by the middle section with no further decline. Experiment 2 compared letter fluency performance among NC, AD and IVD groups, and participants with dementia secondary to idiopathic Parkinsons disease (PD). For all letter cues, IVD and PD participants generated fewer responses than NC and AD participants. However, IVD and PD participants generated a larger proportion of words than AD and NC participants within the first 15 s. As the task progressed, the output of IVD and PD participants dropped precipitously. These findings indicate that failure to maintain mental set is not a diffuse or general cognitive disability. Rather, failure to maintain mental set in dementia may be best understood within the context of predictable and specific within-task time epochs.

Vulnerability of the Orbitofrontal Cortex to Age-Associated Structural and Functional Brain Changes

Abstract:  Cross‐sectional and longitudinal findings from the Baltimore Longitudinal Study of Aging (BLSA) neuroimaging study indicate that the orbitofrontal cortex (OFC) is among those regions vulnerable to age‐associated tissue loss in older adults without dementia. Neuropathologic and recent in vivo amyloid imaging studies indicate that the OFC is also among the earliest neocortical regions to show deposition of amyloid plaques in aging and Alzheimers disease. We performed behavioral and imaging studies to investigate age effects on specific aspects of OFC function. We compared performance in young (age 20–40) and old (age 60 and older) adults on cognitive tasks selected for differential sensitivity to OFC versus dorsolateral prefrontal cortex (DLPFC). Overall, greater age differences were seen in the OFC tasks compared to DLPFC tasks, with Delayed Match and Non‐Match to Sample tasks showing the greatest effect size among OFC tasks and Self‐Ordered Pointing Task showing the greatest effect size among DLPFC tasks. A functional magnetic resonance imaging study was conducted in parallel to probe the neural underpinnings of age differences in OFC function using the Delayed Match and Non‐Match to Sample paradigm. Young but not old adults showed the expected OFC activation. Older compared with young adults showed greater activation in association with successful performance for several posterior regions, perhaps indicating compensation in the face of OFC deficits. Together, these findings indicate a vulnerability of the OFC to age‐related decline in brain structure and function. Future studies using new in vivo imaging probes will help determine whether neuropathologic changes underlie the structural and functional changes.

Effect of type of cognitive task and walking speed on cognitive motor interference during dual-task walking

OBJECTIVE We aimed to determine the effect of distinctly different cognitive tasks and walking speed on cognitive-motor interference of dual-task walking. METHODS Fifteen healthy adults performed four cognitive tasks: visuomotor reaction time (VMRT) task, word list generation (WLG) task, serial subtraction (SS) task, and the Stroop (STR) task while sitting and during walking at preferred-speed (dual-task normal walking) and slow-speed (dual-task slow-speed walking). Gait speed was recorded to determine effect on walking. Motor and cognitive costs were measured. RESULTS Dual-task walking had a significant effect on motor and cognitive parameters. At preferred-speed, the motor cost was lowest for the VMRT task and highest for the STR task. In contrast, the cognitive cost was highest for the VMRT task and lowest for the STR task. Dual-task slow walking resulted in increased motor cost and decreased cognitive cost only for the STR task. CONCLUSIONS Results show that the motor and cognitive cost of dual-task walking depends heavily on the type and perceived complexity of the cognitive task being performed. Cognitive cost for the STR task was low irrespective of walking speed, suggesting that at preferred-speed individuals prioritize complex cognitive tasks requiring higher attentional and processing resources over walking. While performing VMRT task, individuals preferred to prioritize more complex walking task over VMRT task resulting in lesser motor cost and increased cognitive cost for VMRT task. Furthermore, slow walking can assist in diverting greater attention towards complex cognitive tasks, improving its performance while walking.

Age differences in orbitofrontal activation: an fMRI investigation of delayed match and nonmatch to sample.

Several investigations have suggested that the orbitofrontal cortex (OFC) may be particularly vulnerable to the effects of age-related changes. We recently reported behavioral data indicating greater age differences in orbitofrontal tasks when directly compared to tasks tapping dorsolateral prefrontal functions. The present study was designed to investigate the neural underpinnings of age differences in OFC functioning. Event-related functional magnetic resonance imaging (fMRI) was performed during delayed match and nonmatch to sample tasks, previously shown to differentially activate medial and lateral OFC in young adults. Sixteen healthy younger [age = 26.7(5.6)] and 16 healthy older individuals [age = 69.1 + 5.6] with similar levels of education and general cognitive functioning participated in the experiment. Participants chose the stimulus from a pair of stimuli matching a previously viewed target (match to sample) or chose the nontarget item (nonmatch to sample) depending upon a trial-specific instruction word. Consistent with previous studies, SPM99 analyses of the younger age group revealed activation for medial OFC regions during the match task compared to the nonmatch task and lateral OFC activation during the nonmatch task compared to the match task. In contrast, older adults showed prefrontal activation only during the match relative to the nonmatch task and posterior temporal and limbic involvement during the nonmatch relative to the match task. Between-group analyses confirmed within-group results suggesting differential age-related recruitment of prefrontal regions when performing match and nonmatch tasks. Results suggest that OFC recruitment during these cognitive tasks changes with age and should be evaluated within the context of other prefrontal subregions to further define differential age effects on frontal functions.

Verbal Serial List Learning in Mild Cognitive Impairment: A Profile Analysis of Interference, Forgetting, and Errors

Using cluster analysis Libon et al. (2010) found three verbal serial list-learning profiles involving delay memory test performance in patients with mild cognitive impairment (MCI). Amnesic MCI (aMCI) patients presented with low scores on delay free recall and recognition tests; mixed MCI (mxMCI) patients scored higher on recognition compared to delay free recall tests; and dysexecutive MCI (dMCI) patients generated relatively intact scores on both delay test conditions. The aim of the current research was to further characterize memory impairment in MCI by examining forgetting/savings, interference from a competing word list, intrusion errors/perseverations, intrusion word frequency, and recognition foils in these three statistically determined MCI groups compared to normal control (NC) participants. The aMCI patients exhibited little savings, generated more highly prototypic intrusion errors, and displayed indiscriminate responding to delayed recognition foils. The mxMCI patients exhibited higher saving scores, fewer and less prototypic intrusion errors, and selectively endorsed recognition foils from the interference list. dMCI patients also selectively endorsed recognition foils from the interference list but performed similarly compared to NC participants. These data suggest the existence of distinct memory impairments in MCI and caution against the routine use of a single memory test score to operationally define MCI.

Contribution of specific cognitive processes to executive functioning in an aging population

The current study investigated executive function measures emphasizing Alpha Span (ASp) to understand relationships among executive and nonexecutive tasks. Nondemented older participants (N = 417) received a comprehensive cognitive battery. Age and vocabulary adjusted correlations revealed associations among ASp, Wechsler Adult Intelligence Scale--Revised (D. Wechsler, 1981) Digit Span subtests, and fluency tasks. Principal-components analysis with varimax rotation revealed a 4 component solution (86.4% of the variance) with executive variables contributing to all loadings. Calculated component indices were submitted to a regression analysis predicting ASp performance. After accounting for age (6.3% of the variance), Component 3 reflecting brief attention-mental manipulation accounted for 13.4% of ASp variance; Component 1, verbal language ability, 11.5%; Component 2, sustained attention-mental tracking, 1.9%; and Component 4, visuoperceptual spatial organization-planning, 0.9%. Results stress the importance of considering executive and nonexecutive aspects of cognition when conceptualizing executive functioning.

Graph Theory Analysis of Cortical-Subcortical Networks in Late-Life Depression

OBJECTIVES Late-life major depression (LLD) is characterized by distinct epidemiologic and psychosocial factors, as well as medical comorbidities that are associated with specific neuroanatomical differences. The purpose of this study was to use interregional correlations of cortical and subcortical volumes to examine cortical-subcortical structural network properties in subjects with LLD compared with healthy comparison subjects. METHODS This was a cross-sectional neuroimaging study conducted in the general community. We recruited 73 healthy elderly comparison subjects and 53 subjects with LLD who volunteered in response to advertisements. Brain network connectivity measures were generated by correlating regional volumes after controlling for age, gender, and intracranial volume by using the Brain Connectivity Toolbox. RESULTS Results for overall network strength revealed that LLD networks showed a greater magnitude of associations for both positive and negative correlation weights compared with healthy elderly networks. LLD networks also demonstrated alterations in brain network structure compared with healthy comparison subjects. LLD networks were also more vulnerable to targeted attacks compared with healthy elderly comparison subjects, and this vulnerability was attenuated when controlling for white matter alterations. CONCLUSIONS Overall, this study demonstrates that cortical-subcortical network properties are altered in LLD and may reflect the underlying neuroanatomical vulnerabilities of the disorder.