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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Introduction of a normal retinoblastoma (Rb) gene into Rb-deficient lymphoblastoid cells delays tumorigenicity in immunodefective mice

BACKGROUND: We report on structural brain changes during a 5-year period in healthy control and alcoholic men. METHODS: Alcoholic patients (n = 16), from an initial group of 58 who underwent brain magnetic resonance imaging scanning while in treatment, were rescanned with the same acquisition sequence approximately 5 years later. Control subjects (n = 28) spanning the same age range also were scanned twice at a comparable interval. Changes in brain volume were corrected for error due to differences in head placement between scans and expressed as slopes (cubic centimeters per year), percentage of change over baseline for the control subjects, and standardized change for the alcoholic patients. The alcoholic patients varied considerably in the percentage of time that symptoms of alcohol dependence were present and in the amount of alcohol consumed during follow-up. RESULTS: The cortical gray matter diminished in volume over time in the control subjects, most prominently in the prefrontal cortex, while the lateral and third ventricles enlarged. The alcoholic patients showed similar age-related changes with a greater rate of gray matter volume loss than the control subjects in the anterior superior temporal lobe. The amount of alcohol consumed during follow-up predicted the rate of cortical gray matter volume loss, as well as sulcal expansion. The rate of ventricular enlargement in alcoholic patients who maintained virtual sobriety was comparable to that in the control subjects. CONCLUSIONS: During a 5-year period, brain volume shrinkage is exaggerated in the prefrontal cortex in normal aging with additional loss in the anterior superior temporal cortex in alcoholism. The association of cortical gray matter volume reduction with alcohol consumption over time suggests that continued alcohol abuse results in progressive brain tissue volume shrinkage.     

Longitudinal MRI and cognitive change in healthy elderly.

Cross-sectional studies of normal aging indicate an association between memory and hippocampal volume, and between executive functioning and subcortical-frontal circuits. Much less is known, however, about the relationship between longitudinal MRI changes and cognitive decline. The authors hypothesized that longitudinal change in memory would be best predicted by change in hippocampal volumes, whereas change in executive functioning would be best predicted by cortical atrophy and progression of MRI markers of cerebrovascular disease. For this study, 50 healthy elderly subjects underwent structural MRI and cognitive testing at baseline and again at follow-up, with a mean follow-up interval of 45 months. Volumetric MRI measures were hippocampus, cortical gray matter, white matter signal hyperintensity (WMSH), and lacunae. Neuropsychological measures were psychometrically robust composite scores of episodic memory (MEM) and executive functioning (EXEC). Hierarchical multiple regression indicated that a decrease in hippocampus was associated with a decline in MEM, whereas decreased cortical gray matter and increased WMSH were independently associated with a decline in EXEC. Results suggest that in normal aging, cognitive functioning declines as cortical gray matter and hippocampus decrease, and WMSH increases. The association between WMSH and EXEC further highlights the cognitive sequealae associated with cerebrovascular disease in normal elderly. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

News of cognitive cure for age-related brain shrinkage is premature: A comment on Burgmans et al. (2009).

The extant longitudinal literature consistently supports the notion of age-related declines in human brain volume. In a report on a longitudinal cognitive follow-up with cross-sectional brain measurements, Burgmans and colleagues (2009) claim that the extant studies overestimate brain volume declines, presumably due to inclusion of participants with preclinical cognitive pathology. Moreover, the authors of the article assert that such declines are absent among optimally healthy adults who maintain cognitive stability for several years. In this comment accompanied by reanalysis of previously published data, we argue that these claims are incorrect on logical, methodological, and empirical grounds. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationships among aging, IQ, and intracranial volume in alcoholics and control subjects.

The current article examined the relationships among aging, intelligence, intracranial volume, and brain shrinkage in alcoholics and nonalcoholic controls. Magnetic resonance imaging was used to measure intracranial and cerebral volumes in 146 subjects with alcohol use disorders and 42 comparison subjects who were not alcoholic. The authors' findings show that performance on Block Design decreases as alcoholics age, and this decrease is predicted by brain shrinkage. This is consistent with a process of cumulative brain damage related to alcohol use. However, the authors' data also show that vocabulary does not decrease with age and is correlated with premorbid brain size as measured by intracranial volume, suggesting that lower verbal ability precedes heavy alcohol use and may be a risk factor for alcoholism. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible?

Accumulating evidence suggests alterations in brain structure, especially in the prefrontal and temporal cortex, in schizophrenia. Previous studies examining the progression of brain structural alterations in schizophrenia have led to conflicting results. Morphometric studies of the superior temporal gyrus (STG) volumes were conducted in a series of neuroleptic-naive first-episode schizophrenic patients, non-schizophrenic first-episode psychotic patients, and matched healthy controls. Three-dimensional MRI scans were carried out in these subjects before and after one year of treatment. Volume reductions were seen at baseline in the left superior temporal gyrus (adjusted for intracranial volume) in both of the patient groups. Pretreatment illness duration was inversely related to the volume of the left superior temporal gyrus; this relation was confined to males. One-year follow-up MRI investigations in a smaller subset of patients suggested that the STG volume reductions may be reversible. No significant changes were noted in the STG volumes in matched healthy controls who were also scanned at baseline as well as at one-year follow-up. These findings have implications for understanding the nature of the neuropathological processes in early schizophrenia, as well as the potential impact of early treatment.     

Aging, vascular risk, and cognition: Blood glucose, pulse pressure, and cognitive performance in healthy adults.

Advanced age is associated with decline in many areas of cognition as well as increased frequency of vascular disease. Well-described risk factors for vascular disease, such as diabetes and arterial hypertension, have been linked to cognitive deficits beyond those associated with aging. To examine whether vascular health indices such as fasting blood glucose levels and arterial pulse pressure can predict subtle deficits in age-sensitive abilities, the authors studied 104 healthy adults (ages 18 to 78) without diagnoses of diabetes or hypertension. Whereas results revealed a classic pattern of age-related differences in cognition, preprandial blood glucose level and pulse pressure independently and differentially affected cognitive performance. High-normal blood glucose levels were associated with decreased delayed associative memory, reduced accuracy of working memory processing among women, and slower working memory processing among men. Elevated pulse pressure was associated with slower perceptual–motor processing. Results suggest that blood glucose levels and pulse pressure may be sensitive indicators of cognitive status in healthy adults; however, longitudinal research is needed to determine whether such relatively mild elevations in this select group predict age-related cognitive declines. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuroanatomical and cognitive mediators of age-related differences in episodic memory.

Aging is associated with declines in episodic memory. In this study, the authors used a path analysis framework to explore the mediating role of differences in brain structure, executive functions, and processing speed in age-related differences in episodic memory. Measures of regional brain volume (prefrontal gray and white matter, caudate, hippocampus, visual cortex), executive functions (working memory, inhibitory control, task switching, temporal processing), processing speed, and episodic memory were obtained in a sample of young and older adults. As expected, age was linked to reduction in regional brain volumes and cognitive performance. Moreover, neural and cognitive factors completely mediated age differences in episodic memory. Whereas hippocampal shrinkage directly affected episodic memory, prefrontal volumetric reductions influenced episodic memory via limitations in working memory and inhibitory control. Age-related slowing predicted reduced efficiency in temporal processing, working memory, and inhibitory control. Lastly, poorer temporal processing directly affected episodic memory. No direct effects of age on episodic memory remained once these factors were taken into account. These analyses highlight the value of a multivariate approach with the understanding of complex relationships in cognitive and brain aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Executive function and MRI prefrontal volumes among healthy older adults.

Brain atrophy and decline in executive functioning have been reported during late life, but the relationship between the 2 phenomena is not clear. To examine associations between executive tasks and morphometry, MRIs of the prefrontal cortex from 23 healthy elders were manually masked and automatically segmented. Total brain matter of the bilateral orbitofrontal, anterior cingulate, gyrus rectus, precentral gyrus, and middle frontal gyrus were computed as ratios of intracranial volume. A neuropsychological battery of five clinical tests of executive function was administered. Better performance on a response inhibition task was associated with larger volume in anterior cingulate, and performance on a nonverbal inductive reasoning task was associated with larger gyrus rectus volumes. In contrast, larger orbitofrontal volumes were associated with lower verbal and nonverbal generative output. An aggregated error index from 4 executive tests correlated negatively with a regional composite brain index. In conclusion, some executive abilities correlate with volumes of specific prefrontal subregions despite a robust neural interconnectedness between the subregions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparing prefrontal gray and white matter contributions to intelligence and decision making in schizophrenia and healthy controls.

The authors examined the relationship between neuropsychological performance and MRI of the orbital frontal cortex (OFC) and diffusion tensor imaging (DTI) of the cingulum bundle (CB) within groups of patients with schizophrenia and healthy subjects. The authors analyzed data from subjects, who had participated in prior MRI, DTI, and neuropsychological studies (Nakamura et al., 2008; Nestor et al., 2008). In comparison to healthy subjects, patients showed the expected reductions across CB fractional anisotropy (white matter) and OFC gray matter volume as well as lower neuropsychological scores. In addition, in comparison to healthy subjects, patients showed a very different pattern of functional-anatomical correlates. For patients, CB white matter but not OFC gray matter correlated with various aspects of intelligence, including general abilities and working memory. For controls, OFC gray matter but not CB white matter correlated with scores on tests of intelligence and decision making. These results point to the potentially important role of CB white matter in the neuropsychological disturbance in schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age-associated losses of brain volume predict longitudinal cognitive declines over 8 to 20 years.

Absolute differences in global brain volume predict differences in cognitive ability among healthy older adults. However, absolute differences confound lifelong differences in brain size with amounts of age-related shrinkage. Measurements of cerebrospinal fluid (CSF) volume were made to estimate age-related shrinkage in 93 healthy volunteers aged 63 to 86 years. Their current levels of brain shrinkage predicted their amounts of decline over the previous 8 to 20 years on repeated assessments during a longitudinal study on the Cattell "Culture Fair" Intelligence Test, on two tests of information processing speed, and marginally on the Wechsler Adult Intelligence Scale (D. Wechsler, 1981), but not on three memory tests. Loss of brain volume is an effective marker both for current cognitive status and for amounts and rates of previous age-related cognitive losses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibitory control following perinatal brain injury.

Evidence from developmental, lesion, and neuroimaging studies indicates that the prefrontal cortex plays a major role in executive abilities, including inhibitory control. Proficient executive performance, however, relies not only on the integrity of the prefrontal cortex but also on its interactions with other brain regions. In the current study, the authors focused on the effect that early damage to the white matter tracts interconnecting prefrontal and other brain regions has on inhibitory control. Data were collected from 13 children with bilateral spastic cerebral palsy and from a control group of 20 children with no history of neurologic compromise. Converging evidence from 3 separate paradigms is presented that strongly suggests these children experience impairments in inhibitory control. Findings are discussed within the context of current cognitive and neuroanatomical models of inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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 prefrontal 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 risks 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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain Lesion Volume and Neuropsychological Function Predict Efficacy of Treatment for Depression in Multiple Sclerosis.

This study examined the effects of brain lesions and neuropsychological impairment on the efficacy of treatment for depression in patients with comorbid diagnoses of multiple sclerosis (MS) and major depressive disorder (MDD). Thirty patients meeting criteria for MS and MDD received 1 of 3 16-week treatments for depression and were followed for 6 months following treatment cessation. T2-weighted magnetic resonance imaging and neuropsychological evaluations were also obtained. End-of-treatment Beck Depression Inventory (BDI; A. T. Beck, C. H. Ward, M. Mendelson, J. Mock, & J. Erbaugh, 1961) results residualized for baseline BDI were related to right temporal periventricular lesion volume (R2=.32, p=.002) and left temporal grey-white junction lesion volume (R2=.19, p=.02) but were not statistically related to lesion volume in any other brain region or to neuropsychological function. BDI results at 6-month follow-up, residualized for end-of-treatment BDI, were predicted by total lesion volume (R2=.22, p=.005), lesion volume in many discrete areas, and neuropsychological functioning (R2=.29, p=.0009). The effect of total lesion volume on 6-month follow-up BDI results was fully mediated by neuropsychological function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationship of age, age at onset, and sex to depression in older adults

The authors investigated the relationships among factors of age, age at onset, and sex in depressed older adults. A group of 96 outpatients (mean age, 60) diagnosed with late-(LOD) and early-onset (EOD) major depression were assessed for severity of depression and underwent magnetic resonance imaging (MRI). The MRI scans were rated for severity of white-matter hyperintensities (WMH) and ventricle-to-brain ratio (VBR). LOD was associated with increased amounts of WMH, larger VBR, and history of hypertension. Men were more severely depressed than women, with higher rates of neurovegetative signs and history of smoking. Age correlated with increased VBR and WMH, history of hypertension, history of percipitants for the current episode, and lack of social support. Results suggest that a subgroup of men may be more at risk for LOD associated with WMH and that sex and age at onset need to be considered in future studies.     

Cognitive predictors of medical decision-making capacity in traumatic brain injury.

Objective: To identify cognitive predictors of medical decision-making capacity (MDC) in participants with moderate to severe traumatic brain injury (TBI). Participants: At baseline, participants were 34 adults with TBI and 20 healthy adults. At 6-month follow-up, participants were 24 adults with TBI and 20 healthy adults. Main Outcome Measures: Participants were administered the Capacity to Consent to Treatment Instrument (CCTI) and neuropsychological test measures. Multivariate cognitive predictor models were developed for CCTI consent abilities/standards (S) of understanding (S5); reasoning (S4); and appreciation (S3). Results: At baseline, short-term verbal memory and semantic fluency predicted TBI group performance on understanding (S5); short-term verbal memory and attention predicted performance on reasoning (S4); and working memory predicted performance on appreciation (S3). At 6 month follow-up, executive function, verbal processing speed, and working memory predicted TBI performance on understanding (S5); working memory and short-term memory predicted reasoning (S4); and basic executive functioning predicted appreciation (S3). Conclusions: Multiple cognitive functions are associated with acute impairment and partial recovery of MDC in patients with TBI. Short-term verbal memory predicted consent capacity of TBI participants at the time of acute inpatient hospitalization, while executive functioning and working memory predicted improved capacity at six-month follow-up. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive functioning and neuroanatomic volume measures in schizophrenia.

Magnetic resonance imaging (MRI) and neuropsychological tests were administered to 68 patients with schizophrenia and 68 healthy controls. MRIs were analyzed with a partially automated segmentation method that quantifies the volume of each cerebral hemisphere and its cerebrospinal fluid (CSF). Whereas patients had higher ventricular-brain ratio (VBR), ventricular CSF (vCSF) volume was equivalent to controls. Brain volume was lower. Cognitive function did not correlate with VBR or vCSF volume in either group, but cognitive function did correlate with brain volume. Divided as deficit (DF) and nondeficit (NDF), only DF patients had lower brain volume than controls. Whereas NDF patients showed little correlation between anatomy and cognitive function, there were more correlations between brain volume and cognition in DF patients. Changes in DF/NDF subtype with time and treatment reduced the significance of these findings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The structure of depression among elderly institution residents: affective and somatic correlates of physical frailty

BACKGROUND: Confounding of depression with somatic illness and anxiety, a problem in any age group, may be especially troublesome in frail older persons. This paper examined this problem in a factor analytic study of the structure of depressive symptomatology, identifying affective and somatic symptom clusters and relating those clusters to health and functional variables cross-sectionally and prospectively over a 1-year interval. METHODS: The factor structure of a DSM-IV symptom checklist was examined among 1,245 elderly long-term care residents. Regression analyses examined the association of resulting factors with cognition, functional disability, self- and physician-rated health, and pain at baseline and a year later. One-year mortality was also examined. RESULTS: Factor analysis revealed three unique symptom clusters: depressed mood, somatic symptoms, and psychic anxiety. Depressed mood and somatic symptoms were associated cross-sectionally with all functional health variables, but psychic anxiety was associated only with pain. Longitudinally, depressed mood was the only independent predictor of decline in cognition, functional ability, physician-rated health, and mortality; the last effect, however, did not withstand control for baseline health and functioning. Somatic symptoms at baseline predicted decrement in self-rated health a year later. Effects varied as a function of cognitive status. CONCLUSIONS: These data suggest that concerns about the confounding role of somatic symptoms in the association of depression with physical health are unfounded. Although somatic symptoms of depression and anxiety were associated with health and functional status cross-sectionally, depressed mood was by far the stronger predictor of health declines over time.     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)