Cortical gray matter atrophy in healthy aging cannot be explained by undetected incipient cognitive disorders: A comment on Burgmans et al. (2009).

Burgmans, van Boxtel, Vuurman, et al. (2009) published an interesting study titled “The Prevalence of Cortical Gray Matter Atrophy May Be Overestimated in the Healthy Aging Brain” on how subclinical cognitive disorders may affect correlations between age and cortical volume. Correlations between cortical gray matter volume and age were found in 30 elderly with cognitive decline after 6 years, but not in 28 elderly without cognitive decline. This study is important, and demonstrates that preclinical cognitive disorders may affect cortical brain volumes before being detectable by neuropsychological tests. However, we are not convinced by the conclusions: “… gray matter atrophy… is to a lesser extent associated with the healthy aging process, but more likely with brain processes underlying significant cognitive decline” (p. 547) and “… cortical gray matter atrophy in the aging brain may be overestimated in a large number of studies on healthy aging” (p. 547). We analyzed the cross-sectional MR data (n = 1,037) as well as longitudinal data from a sample of very well-screened elderly followed by cognitive testing for 2 years. In the cross-sectional data, the correlations between age and brain volumes were generally not much reduced when the upper age limit was lowered. This would not be expected if age-related incipient cognitive disorders caused the correlations given that the incidence of cognitive decline increased with age. Longitudinally, 1-year atrophy was identified in all tested regions. It is likely that cortical brain atrophy is manifested in cognitively normal elderly without subclinical cognitive disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aging does not affect gray matter asymmetry.

Previous research has shown that asymmetry of brain activity is decreased in older adults. This study investigates whether cortical gray matter asymmetry also shows age-related differences, and whether gray matter asymmetry differs between cognitively stable persons and persons who have shown profound age-related declines in cognitive functioning. In addition, we have examined whether prodromal dementia affects the study outcome. The gray matter volumes of seven prefrontal and temporal regions of interest were delineated on T1-weighted MRI scans in 70 adults aged between 52 and 84 years. Statistical analyses were conducted with and without participants who developed dementia within 6 years after the MRI scan session. It was found that asymmetry did not differ over the age range of 52–84 years of age. This result did not change when data from participants who were diagnosed with dementia within 6 years after MRI assessment were excluded from the analysis. In addition, no gray matter asymmetry differences were found between cognitively stable participants and participants who showed cognitive decline. We conclude that alterations in gray matter asymmetry may not be part of the healthy aging process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The prevalence of cortical gray matter atrophy may be overestimated in the healthy aging brain.

Prevailing opinion holds that normal brain aging is characterized by substantial atrophy of cortical gray matter. However, this conclusion is based on earlier studies whose findings may be influenced by the inclusion of subjects with subclinical cognitive disorders like preclinical dementia. The present magnetic resonance imaging study tested this hypothesis. Cognitively healthy subjects (mean age 72 years, range 52–82) who remained cognitively stable over a 3-year period were compared to subjects with significant cognitive decline. Subjects who developed dementia within 6 years after the scan session were excluded. The gray matter volumes of seven cortical regions were delineated on T1-weighted magnetic resonance imaging scans. Participants without cognitive decline did not exhibit an age effect on the gray matter volume. Conversely, participants with cognitive decline exhibited a significant age effect in all the seven areas. These results suggest that cortical gray matter atrophy may have been overestimated in studies on healthy aging, since most studies were unable to exclude participants with a substantial atypical cognitive decline or preclinical dementia. Our results underscore the importance of establishing stringent inclusion criteria for future studies on normal aging. (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)     

Preserved neuron number in the hippocampus of aged rats with spatial learning deficits

Hippocampal neuron loss is widely viewed as a hallmark of normal aging. Moreover, neuronal degeneration is thought to contribute directly to age-related deficits in learning and memory supported by the hippocampus. By taking advantage of improved methods for quantifying neuron number, the present study reports evidence challenging these long-standing concepts. The status of hippocampal-dependent spatial learning was evaluated in young and aged Long-Evans rats using the Morris water maze, and the total number of neurons in the principal cell layers of the dentate gyrus and hippocampus was quantified according to the optical fractionator technique. For each of the hippocampal fields, neuron number was preserved in the aged subjects as a group and in aged individuals with documented learning and memory deficits indicative of hippocampal dysfunction. The findings demonstrate that hippocampal neuronal degeneration is not an inevitable consequence of normal aging and that a loss of principal neurons in the hippocampus fails to account for age-related learning and memory impairment. The observed preservation of neuron number represents an essential foundation for identifying the neurobiological effects of hippocampal aging that account for cognitive decline.     

Selective cortical and hippocampal volume correlates of Mattis Dementia Rating Scale in Alzheimer disease

OBJECTIVE: To examine whether each of the 5 Mattis Dementia Rating Scale (DRS) scores related to magnetic resonance imaging-derived volumes of specific cortical or limbic brain regions in patients with Alzheimer disease (AD). DESIGN: Relations between DRS measures and regional brain volume measures were tested with bivariate and multivariate regression analyses. SETTING: The Aging Clinical Research Center of the Stanford (Calif) University Department of Psychiatry and Behavioral Science and the Geriatric Psychiatry Rehabilitation Unit of the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif. PATIENTS AND OTHER PARTICIPANTS: Fifty patients with possible or probable AD. Magnetic resonance imaging data from 136 healthy control participants, age 20 to 84 years, were used to correct brain volumes for normal variation arising from intracranial volume and age. MAIN OUTCOME MEASURES: The DRS scores and volumes of regional cortical gray matter and of the hippocampus. RESULTS: Memory scores of the patients with AD were selectively related to hippocampal volumes. Attention and construction scores were related to several anterior brain volume measures, with attention showing a significantly greater association to right than left hemisphere measures. Initiation/perseveration scores were not significantly correlated with any measure of regional gray matter volume, but performance was related to prefrontal sulcal widening, with a greater association with the left than right sulcal volume. CONCLUSIONS: Certain DRS subtests are predictably correlated with selective regional brain volumes in AD. The specific relation between memory and hippocampal volumes and the nonsignificant relations between memory and regional cortical volumes suggest a dissociation between cortical and hippocampal contributions to explicit memory performance.     

The Stimulation Program Health Research. X. Evaluation of the program section 'Psychogeriatrics'

In the programme section 'Psychogeriatrics' of the SGO Health Research Promotion Programme a longitudinal study was carried out in Amsterdam from 1989 until 1994, concerning the course of mild cognitive decline in elderly people (the AMSTEL project). The scientific aims were the development of diagnostical instruments for the early diagnosis of dementia, the development of criteria which predict the course of mild cognitive impairment and the expansion of knowledge on the relationship between somatic and psychiatric pathology and dementia. The programme also had aims regarding medical education and patient care. The results include the following: in order to diagnose dementia in general practice questions regarding orientation and short-term memory are helpful. Risk factors for cognitive deterioration in elderly people include hippocampal atrophy on the MRI scan, a low level of education and subjective complaints regarding memory. Subjective complaints regarding memory are not primarily caused by a depressive mood, as is often thought, but are important as correct self-observations of cognitive deterioration, and go with an increased risk of developing dementia. Besides the AMSTEL project a feasibility study was carried out concerning a psychogeriatric case register in Amsterdam.     

Studying Individual Aging in an Interindividual Context: Typical Paths of Age-Related, Dementia-Related, and Mortality-Related Cognitive Development in Old Age.

This study has 2 objectives: (a) to explore typical paths of cognitive development associated with aging, terminal decline, and dementia and (b) to promote and illustrate an individual-oriented approach to the study of cognitive aging based on longitudinal panel data from a population-based sample (N = 500; age rangeT1= 60-80, where T refers to time) tested at 3 occasions 5 years apart. Results document interindividual differences in multivariate patterns of change. Although cognitive changes generally covary, the present study indicates that subgroups of individuals develop along different paths characterized by selective changes in subsets of cognitive functions. Typical progression of dementia followed a developmental cascade from low declarative memory, via low functioning across all observed cognitive measures, to dementia diagnosis, and finally, death. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

MRI signal hyperintensities in geriatric depression

OBJECTIVE: The authors rated periventricular and subcortical signal hyperintensities on magnetic resonance imaging (MRI) scans in elderly patients with depression and in normal subjects with similar demographic features to examine whether such changes discriminate patients with depression from normal subjects and whether they are associated with any clinical variables. METHOD: Two established hyperintensity rating systems were used to compare the MRI brain scans of 48 elderly patients with depression diagnosed according to DSM-III-R with the scans of 39 normal elderly subjects. RESULTS: Elderly depressed patients manifested significantly more severe hyperintensity ratings in the subcortical gray matter than age-matched comparison subjects. Significant differences were not identified between patients with similar current ages and cerebrovascular disease risk who had early-onset or late-onset depression. CONCLUSIONS: These findings support those of neuroimaging studies implicating the basal ganglia in depression and geriatric depression. The data suggest that the relationship observed in some reports between late-onset depression and MRI hyperintensities is most likely a function of cerebrovascular disease risk and age.     

Apolipoprotein E and Prospective Memory in Normally Aging Adults.

The ε4 allele of apolipoprotein E (APOE) is an established risk factor for Alzheimer's disease, despite uncertainty as to its effect on cognitive function in normal aging. Some evidence suggests poor episodic memory and executive functioning in ε4 allele carriers. Prospective memory has been overlooked in investigations of the relationship between APOE and cognition. The authors used a laboratory paradigm to examine the relationship between prospective memory and APOE status in healthy elderly adults, and they varied the association (high vs. low) between a target word and a response word. The authors found a significant deficit in prospective memory for ε4 allele carriers but no effect of association in either group. The results suggest the deficit was due to failure of the prospective component of the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dysfunctional uterine bleeding

Alzheimer's disease (AD) is characterized by progressive dementia and distinct neuropathology at autopsy. In order to test the relationship between dementia severity and loss of brain volumes, we prospectively documented the neurological/medical health of 26 male and 26 female controls and AD cases, and evaluated a subset of controls and AD cases using the Mini Mental State Examination (MMSE). At autopsy, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria confirmed diagnoses in 33 AD cases and 19 controls, and using unbiased stereology we quantified total volumes of cortical gray matter, subcortical grey matter including white matter, and forebrain. For ages of death between 50 to 100 years, controls showed minor cortical atrophy in the absence of cognitive decline. Cortical atrophy in AD cases was 20 to 25% greater than that in controls; AD patients dying at older ages showed less severe cortical atrophy than those dying at younger ages. Across all AD cases there was a strong correlation between cognitive performance on the Mini Mental State Examination and cortical volume loss. These findings confirm fundamental differences in the temporal patterns of cortical volume loss in aging and AD, and support cortical degeneration as the primary basis for cognitive decline in AD.     

Management of primary chest wall tuberculosis

The elderly are persons over age 65, now comprising 12% of our population. The normal elderly function normally both in their self care, and also in their social activities of daily living, which we tabulate. The current terms for the normally functioning elderly who show only mild psychological deficits are age-associated memory impairment and age-related cognitive decline, which we define, criticize and tabulate. The psychological deficits of the elderly consist of mild generalized slowing and inaccuracies compared to normal young persons. These deficits are measured by objective psychological tests which mimic real daily living situations--the name-face test, fire alarm test, two delayed recall tests, misplaced objects test, shopping list test, and digit symbol test, which we describe. A longer early formal education is preventive of mental dulling during normal aging. Treating using overlearning, by cognitive training, is significantly beneficial.     

Heterogeneity of cognitive trajectories in diverse older persons.

This study examined trajectories of cognitive change in psychometrically matched measures of episodic memory, semantic memory, and executive function in an ethnically, demographically, and cognitively diverse sample of older persons. Individual rates of change showed considerable heterogeneity in each domain. Baseline clinical diagnosis predicted differential change in semantic memory and executive function, dementia > mild cognitive impairment (MCI) > normal, but average decline in verbal episodic memory was similar across all 3 diagnostic groups. There was substantial overlap of distributions of cognitive change across baseline diagnostic groups for all 3 measures. Cognitive change was strongly related to change in clinical diagnosis. Rapid and similar change was present for all 3 cognitive measures in patients with dementia and in those with normal cognition and those with MCI who progressed clinically. In cognitively normal patients, verbal episodic memory change was greater than change in the other two domains. Global status, measured by the Clinical Dementia Rating scale (Morris, 1993), predicted change in semantic memory and executive function, whereas APOE genotype predicted change in verbal episodic memory, and age had no effect on rates of change in any domain independent of global status and APOE. Results show important limitations in using cross-sectional diagnosis to predict prognosis and suggest that research to identify robust predictors of cognitive change across the full spectrum from normal to dementia is needed for better early identification of diseases that cause progressive decline. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of New York''s bypass surgery provider profiling on access to care and patient outcomes in the elderly

OBJECTIVES: To determine the annual rates of volumetric change of the hippocampus and temporal horn in cognitively normal elderly control subjects and individually matched patients with AD, and to test the hypothesis that these rates were different. BACKGROUND: Cross-sectional studies consistently reveal cerebral atrophy in elderly nondemented subjects compared with healthy young adults, and greater atrophy in patients with AD relative to elderly control subjects. However, rates of atrophy are estimated most accurately by performing serial measurements in the same individuals. METHODS: MRI-based volumetric measurements of the hippocampi and temporal horns were performed in 24 cognitively normal subjects aged 70 to 89 years who were individually matched with respect to gender and age with 24 patients with AD. Each subject underwent an MRI protocol twice, separated by 12 months or more. RESULTS: The mean annual rate of hippocampal volume loss among control subjects was -1.55+/-1.38% and the temporal horns increased in volume by 6.15+/-7.69% per year. These rates were significantly greater among AD patients: hippocampus, -3.98+/-1.92% per year, p < 0.001; temporal horn, 14.16+/-8.47% per year, p = 0.002. CONCLUSION: A statistically significant yearly decline in hippocampal volume and an increase in temporal horn volume was identified in elderly control subjects who represent typical aging individuals. These rates were approximately 2.5 times greater in patients with AD than in individually age- and gender-matched control subjects.     

Stem-cell-associated structural and functional plasticity in the aging hippocampus.

Aging frequently leads to a functional decline across multiple cognitive domains, often resulting in a severe reduction in life quality and also causing substantial care-related costs. Understanding age-associated structural and functional changes of neural circuitries within the brain is required to improve successful aging. In this review, the authors focus on age-dependent alterations of the hippocampus and the decline of hippocampal function, which are critically involved in processes underlying certain forms of learning and memory. Despite the dramatic reductions in hippocampus-dependent function that accompany advancing age, there is also striking evidence that even the aged brain retains a high level of plasticity. Thus, one promising avenue to reach the goal of successful aging might be to boost and recruit this plasticity, which is the interplay between neural structure, function, and experience, to prevent age-related cognitive decline and age-associated comorbidities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in the relationship between visual memory and MRI hippocampal volumes.

This study investigated sex differences in the relationships between visual memory and MRI-determined hippocampal volume data before and after right and left temporal lobectomy (TL). Preoperative visual memory and postoperative visual memory change were evaluated by the Wechsler Memory Scale-Revised, and MRI hippocampal volumes were obtained in 54 right (28 men and 26 women) and 75 left (33 men, 42 women) TL patients. Preoperative visual memory and postoperative visual memory change were significantly related to the difference between hippocampal volumes (DHV) in right TL women but not right TL men. That is, extirpation of a large right hippocampus was significantly associated with a visual memory decline, but only in women. These findings support the presence of sexually dimorphic brain function and suggest that visual memory ability in women may be less plastic after a developmentally early right mesial temporal insult. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Longitudinal deficits to attention, executive, and working memory in subtypes of mild cognitive impairment.

Objective: Mild cognitive impairment (MCI) has emerged as a classification for a prodromal phase of cognitive decline that may precede the emergence of Alzheimer's disease (AD). Recent research suggests that attention, executive, and working memory deficits may appear much earlier in the progression of AD than traditionally conceptualized, and may be more consistently associated with the later development of AD than memory processing deficits. The present study longitudinally tracked attention, executive and working memory functions in subtypes of MCI. Method: In a longitudinal study, 52 amnestic MCI (a-MCI), 29 nonamnestic MCI (na-MCI), and 25 age- and education-matched controls undertook neuropsychological assessment of visual and verbal memory, attentional processing, executive functioning, working memory capacity, and semantic language at 10 month intervals. Results: Analysis by repeated measures ANOVA indicate that the a-MCI and na-MCI groups displayed a decline in simple sustained attention (ηp2 = .054) with a significant decline on a task of divided attention (ηp2 = .053) being evident in the a-MCI group. Stable deficits were found on other measures of attention, working memory and executive function in the a-MCI and na-MCI groups. The a-MCI group displayed stable impairments to visual and verbal memory. Conclusions: The results indicate that a-MCI and na-MCI display a stable pattern of deficits to attention, working memory, and executive function. The decline in simple sustained attention in a-MCI and n-MCI groups and to divided attention in a-MCI may be early indicators of possible transition to dementia from MCI. However, further research is required to determine this. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Partial hippocampal inactivation: Effects on spatial memory performance in aged and young rats.

Changes in anatomical or functional connectivity during normal aging are thought to contribute to cognitive alterations over the lifespan. Neural network theories predict that synaptic loss in an aging brain could place the organism near the point of dysfunction in the nonlinear curve defining neural compromise versus performance. The present experiments examined whether aged rats are closer to this point of behavioral dysfunction by reversibly inactivating one or both hippocampal hemispheres. As expected, bilateral tetracaine inactivation of the hippocampus disrupted spatial memory in both age groups. Unilateral left hippocampal inactivation significantly increased errors only in aged rats; however, unilateral inactivation of the right hippocampus had no effect. The present outcome could reflect more extensive synaptic dysfunction in the aged right hippocampus or a greater involvement of the left hippocampus in spatial working memory problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive estimation impairment in Alzheimer disease and mild cognitive impairment.

Intact executive functioning is believed to be required for performance on tasks requiring cognitive estimations. This study used a revised version of a cognitive estimations test (CET) to investigate whether patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) were impaired on the CET compared with normal elderly controls (NECs). Neuropsychological tests were administered to determine the relationship between CET performance and other cognitive domains. AD patients displayed impaired CET performance when compared with NECs but MCI patients did not. Negative correlations between tests of working memory (WM) and semantic memory and the CET were found in NECs and AD patients, indicating that these cognitive domains were important for CET performance. Regression analysis suggests that AD patients were unable to maintain semantic information in WM to perform the task. The authors conclude that AD patients display deficits in working memory, semantic memory, and executive function, which are required for adequate CET performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aging, episodic memory feeling-of-knowing, and frontal functioning.

Groups of normal old and young adults made episodic memory feeling-of-knowing (FOK) judgments and took 2 types of episodic memory tests (cued recall and recognition). Neuropsychological tests of executive and memory functions thought to respectively involve the frontal and medial temporal structures were also administered. Age differences were observed on the episodic memory measures and on all neuropsychological tests. Compared with young adults, older adults performed at chance level on FOK accuracy judgments. Partial correlations indicated that a composite measure of frontal functioning and FOK accuracy were closely related. Hierarchical regression analyses showed that the composite frontal functioning score accounted for a large proportion of the age-related variance in FOK accuracy. This finding supports the idea that the age-related decline in episodic memory FOK accuracy is mainly the result of executive or frontal limitations associated with aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)