***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVES To investigate longitudinal associations between changes in brain structure and gait decline  . DESIGN Longitudinal . SETTING Population -based Tasmanian Study of Cognition and Gait . PARTICIPANTS Two hundred twenty-five individuals aged 60 to 86 ( mean age 71.4 ± 6.8 ) r and omly selected from the electoral roll with baseline and follow-up data . MEASUREMENTS Volumes of gray matter , white matter , hippocampi , and white matter lesions ( WML ) were estimated using automated segmentation from magnetic resonance imaging ( MRI ) .  Gait variables were measured using a computerized walkway . Linear regression was used to estimate the association between change in brain MRI measures and change in gait . Time between measurements , age , sex , BMI , education level , total intracranial volume , baseline infa rcts , and medical history were used as baseline covariates . RESULTS Mean follow-up was 30.6 months . White matter atrophy was associated with a decline in gait speed ( P = .001 ) , step length ( P = .005 ) , and cadence ( P = .001 ) . WML progression was associated with a decline in gait speed ( P = .04 ) , and its association with decline in step length was stronger with greater baseline age ( P for interaction = .04 ) . Hippocampal atrophy was associated with a decline in gait speed ( P = .006 ) and step length ( P = .001 ) . Total gray matter atrophy was associated with decline in cadence in those with cerebral infa rcts ( P for interaction = .02 ) . CONCLUSION These are the first longitudinal data demonstrating the relative contributions of brain atrophy and WML progression to gait decline in older people . Effect modification according to age and infa rcts suggests a contribution of reduced physiological and brain reserve . Interventions targeting brain health may be important in preventing mobility decline in older people Magnetic Resonance Imaging ( MRI ) provides a noninvasive method for investigating brain morphology . Within the medial temporal lobe , special attention has been paid to the hippocampus ( HC ) and amygdala ( AG ) because of their role in memory , depression , emotion , and learning . Volume changes in these areas have been observed in conjunction with certain disease states , e.g. Alzheimer 's disease , post-traumatic stress disorder , and depression . Aging has also been shown to result in gray matter volume loss of the overall brain , including the HC . With regard to gender specificity , results suggest a larger shrinkage for men of brain gray matter , with controversial observations being made for the HC . With recently refined MRI acquisition and segmentation protocol s , the HC and AG of 80 subjects in early adulthood ( 39 men and 41 women , age 18–42 years ) were investigated . Whereas the volume of the AG appeared to be independent of age and gender , a significant negative correlation with age for both left and right HC was found in men ( r = −0.47 and −0.44 , respectively ) but not in women ( r = 0.01 and 0.02 , respectively ) . The volume decline in men appeared to be linear , starting at the beginning of the third life decade and approximating 1.5 % per annum . Using voxel-based regressional analysis , it was shown that changes with age occurred mostly in the head and tail of the HC . This finding underscores the need to include sociodemographic variables in functional and anatomical MRI design Background and Purpose : Defining how brain structures differ in pre- clinical dementia is important to better underst and the pathological processes involved and to inform clinical practice . The aim of this study was to identify significant brain correlates ( volume and asymmetry in volume ) of mild cognitive disorders when compared to normal controls in a large community-based sample of young-old individuals who were assessed for cognitive impairment . Methods : Cortical and sub-cortical volumes were measured using a semi-automated method in 398 participants aged 64–70 years who were selected from a larger r and omly sample d cohort and who agreed to undergo an MRI scan .  Diagnoses were reached based on established protocol s for MCI and a more inclusive category of any Mild Cognitive Disorder ( any-MCD : which includes AAMI , AACD , OCD , MNC , CDR , MCI ) . Logistic regression analyses were used to assess the relationship between volume and asymmetry of theoretically relevant cerebral structures ( predictors ) and MCI or any-MCD while controlling for age , sex , and intra-cranial volume . Results : The main correlates of cognitive impairment assessed in multivariate analyses were hippocampal asymmetry ( more to left , MCI : OR 0.83 , 95%CI 0.71–0.96 , p = 0.013 ; MCD : OR 0.86 , 95%CI 0.77–0.97 , p = 0.011 ) , lateral ventricle asymmetry ( more to left , MCI : OR 0.95 , 95%CI 0.91–0.99 , p = 0.009 ; MCD : OR 0.95 , 95%CI 0.92–0.98 , p = 0.004 ) , and cerebellar cortex asymmetry ( more to right , MCI : OR 1.51 , 95%CI 1.13–2.01 , p = 0.005 ) . Conclusions : In this population -based cohort stronger associations were found between asymmetry measures , rather than raw volumes in cerebral structures , and mild cognitive disorders We detected and mapped a dynamically spreading wave of gray matter loss in the brains of patients with Alzheimer 's disease ( AD ) . The loss pattern was visualized in four dimensions as it spread over time from temporal and limbic cortices into frontal and occipital brain regions , sparing sensorimotor cortices . The shifting deficits were asymmetric ( left hemisphere > right hemisphere ) and correlated with progressively declining cognitive status ( p < 0.0006 ) . Novel brain mapping methods allowed us to visualize dynamic patterns of atrophy in 52 high-resolution magnetic resonance image scans of 12 patients with AD ( age 68.4 ± 1.9 years ) and 14 elderly matched controls ( age 71.4 ± 0.9 years ) scanned longitudinally ( two scans ; interscan interval 2.1 ± 0.4 years ) . A cortical pattern matching technique encoded changes in brain shape and tissue distribution across subjects and time . Cortical atrophy occurred in a well defined sequence as the disease progressed , mirroring the sequence of neurofibrillary tangle accumulation observed in cross sections at autopsy . Advancing deficits were visualized as dynamic maps that change over time . Frontal regions , spared early in the disease , showed pervasive deficits later ( > 15 % loss ) . The maps distinguished different phases of AD and differentiated AD from normal aging . Local gray matter loss rates ( 5.3 ± 2.3 % per year in AD v 0.9 ± 0.9 % per year in controls ) were faster in the left hemisphere ( p < 0.029 ) than the right . Transient barriers to disease progression appeared at limbic/frontal boundaries . This degenerative sequence , observed in vivo as it developed , provides the first quantitative , dynamic visualization of cortical atrophic rates in normal elderly population s and in those with dementia Background : Neuroimaging measures have potential as surrogate markers of disease through identification of consistent features that occur prior to clinical symptoms . Despite numerous investigations , especially in relation to the transition to clinical impairment , the regional pattern of brain changes in clinical ly normal older adults has not been established . We predict that the regions that show early pathologic changes in association with Alzheimer disease will show accelerated volume loss in mild cognitive impairment ( MCI ) compared to normal aging . Methods : Through the Baltimore Longitudinal Study of Aging , we prospect ively evaluated 138 nondemented individuals ( age 64–86 years ) annually for up to 10 consecutive years . Eighteen participants were diagnosed with MCI over the course of the study . Mixed-effects regression was used to compare regional brain volume trajectories of clinical ly normal individuals to those with MCI based on a total of 1,017 observations . Results : All investigated volumes declined with normal aging ( p < 0.05 ) . Accelerated change with age was observed for ventricular CSF ( vCSF ) , frontal gray matter , superior , middle , and medial frontal , and superior parietal regions ( p ≤ 0.04 ) . The MCI group showed accelerated changes compared to normal controls in whole brain volume , vCSF , temporal gray matter , and orbitofrontal and temporal association cortices , including the hippocampus ( p ≤ 0.04 ) . Conclusion : Although age-related regional volume loss is apparent and widespread in nondemented individuals , mild cognitive impairment is associated with a unique pattern of structural vulnerability reflected in differential volume loss in specific regions . Early identification of patterns of abnormality is of fundamental importance for detecting disease onset and tracking progression Experimental and human data suggest that progressive cerebral damage may result from the cumulative effect of brief recurrent seizures . Longitudinal studies addressing this fundamental question , however , are lacking . We have addressed this need with a large prospect i ve community-based observational study , which aims to rescan 154 patients with chronic active epilepsy and 90 patients with newly diagnosed seizures , after an interval of 3.5 years . Here , we describe the quantitative magnetic resonance methods used to identify subtle volume changes in hippocampal , cerebellar , and neocortical structures over time and report preliminary findings . Using this methodology , we have previously shown that we can reliably detect individual hippocampal volume ( HV ) and cerebellar volume ( CBV ) changes greater than 3.1 and 3.0 % , respectively ( Lemieux et al , 2000 ) . Analysis of the first 53 subjects ( 24 patients with chronic active epilepsy , 9 patients with newly diagnosed seizures , and 20 controls ) has demonstrated significant HV losses in 4 individuals . Automated and semiautomated calculation has detected significant reductions in CBV , total brain volume , and gray matter volume in 2 , 3 , and 1 subject , respectively . There were no significant white matter volume losses detected . Data collected from rescanning the entire cohorts will help to provide further information on the relationship between recurrent seizures and secondary brain damage Brain aging research relies mostly on cross-sectional studies , which infer true changes from age differences . We present longitudinal measures of five-year change in the regional brain volumes in healthy adults . Average and individual differences in volume changes and the effects of age , sex and hypertension were assessed with latent difference score modeling . The cau date , the cerebellum , the hippocampus and the association cortices shrunk substantially . There was minimal change in the entorhinal and none in the primary visual cortex . Longitudinal measures of shrinkage exceeded cross-sectional estimates . All regions except the inferior parietal lobule showed individual differences in change . Shrinkage of the cerebellum decreased from young to middle adulthood , and increased from middle adulthood to old age . Shrinkage of the hippocampus , the entorhinal cortices , the inferior temporal cortex and the prefrontal white matter increased with age . Moreover , shrinkage in the hippocampus and the cerebellum accelerated with age . In the hippocampus , both linear and quadratic trends in incremental age-related shrinkage were limited to the hypertensive participants . Individual differences in shrinkage correlated across some regions , suggesting common causes . No sex differences in age trends except for the cau date were observed . We found no evidence of neuroprotective effects of larger brain size or educational attainment OBJECTIVE To determine whether magnetic resonance imaging measurements observed in the Alzheimer Disease Neuroimaging Initiative ( ADNI ) convenience sample differ from those observed in the Mayo Clinic Study of Aging ( MCSA ) population -based sample . DESIGN Comparison of 2 sample s. SETTING Fifty-nine recruiting sites for the ADNI in the United States and Canada and the MCSA , a population -based cohort in Olmsted County , Minnesota . PATIENTS Cognitively normal subjects and amnestic subjects with mild cognitive impairment were selected from the ADNI convenience cohort and MCSA population -based cohort . A simple r and om sample of subjects from both cohorts in the same age range was selected , and a second sample applied matching for age , sex , educational level , apolipoprotein E genotype , and Mini-Mental State Examination score . MAIN OUTCOME MEASURES Baseline hippocampal volumes and annual percentage of decline in hippocampal volume . RESULTS In the population -based sample , MCSA subjects were older , had less education , performed worse on the Mini-Mental State Examination , and had a family history of Alzheimer disease less often than did ADNI subjects . Baseline hippocampal volumes were larger in ADNI compared with MCSA cognitively normal subjects in the r and om sample , although no differences were observed after matching . Rates of decline in hippocampal volume were greater in the ADNI compared with the MCSA for cognitively normal subjects and those with amnestic mild cognitive impairment , even after matching . CONCLUSIONS Rates of decline in hippocampal volume suggest that ADNI subjects have a more aggressive brain pathologic process than MCSA subjects and hence may not be representative of the general population . These findings have implication s for treatment trials that use ADNI-like recruitment mechanisms and for studies validating new diagnostic criteria for Alzheimer disease in its various stages OBJECTIVE According to the stress-toxicity hypothesis of depression , hippocampal volumes may diminish as the disease progresses . We sought to examine the changes in hippocampal and amygdala volumes at baseline and at 3 years after an acute depressive episode , and the impact 
    Output:
    
CONCLUSIONS Hippocampal atrophy rates increase with age with the largest increases occurring from midlife onwards .
Manual segmentation approaches result in higher measured atrophy rates