Left anterior temporal lobe sustains naming in Alzheimer's dementia and mild cognitive impairment

Cognitive decline in degenerative dementia is paralleled by progressive brain atrophy, with the localization of atrophy reflecting specific cognitive impairment. Confrontation naming deficits are frequently observed in dementia across etiologies. In this study we aimed to identify the brain regions underlying this deficit. In patients with clinically diagnosed dementia or mild cognitive impairment (MCI) we investigated the relationship between gray matter volume (GMV) and performance on a standardized confrontation naming test. 268 patients with one of three probable etiologies were included: Alzheimer's Dementia (AD), AD with signs of cerebrovascular pathology, and frontotemporal dementia. Applying voxel-based morphometry using a diffeomorphic registration algorithm we contrasted GMV of patients performing within the normal range with those of patients with pathological performance. Further, differential effects of gray matter atrophy on impaired performance in AD versus MCI of AD type were investigated. Results revealed significantly reduced GMV in the left anterior temporal lobe (ATL) in pathological performers compared to normal performers. The subgroup analysis confined to MCI of AD type and AD patients confirmed this relationship. While left ATL atrophy is known to be implicated in naming deficits in semantic dementia, our data confirm the same in AD and MCI of AD type.     

Volumetric MRI predicts rate of cognitive decline related to AD and cerebrovascular disease

OBJECTIVE: To examine volumetric MRI correlates of longitudinal cognitive decline in normal aging, AD, and subcortical cerebrovascular brain injury (SCVBI). BACKGROUND: Previous cross-sectional studies examining the relationship between cognitive impairment and dementia have shown that hippocampal and cortical gray matter atrophy are the most important predictors of cognitive impairment, even in cases with SCVBI. The authors hypothesized that hippocampal and cortical gray matter volume also would best predict rate of cognitive decline in cases with and without SCVBI. METHODS: Subjects were recruited for a multicenter study of contributions to dementia of AD and SCVBI. The sample (n = 120) included cognitively normal, cognitively impaired, and demented cases with and without lacunes identified by MRI. Cases with cortical strokes were excluded. Average length of follow-up was 3.0 years. Measures of hippocampal volume, volume of cortical gray matter, presence of subcortical lacunes, and volume of white matter hyperintensity were derived from MRI. Random effects modeling of longitudinal data was used to assess effects of baseline MRI variables on longitudinal change in a measure of global cognitive ability. RESULTS: Cortical gray matter atrophy predicted cognitive decline regardless of whether lacunes were present. Hippocampal atrophy predicted decline only in those without lacunes. Neither lacunes nor white matter hyperintensity independently predicted decline. CONCLUSIONS: Results suggest that cortical atrophy is an index of disease severity in both AD and subcortical cerebrovascular brain injury and consequently predicts faster progression. Hippocampal volume may index disease severity and predict progression in AD. The absence of this effect in cases with lacunes suggests that this group is etiologically heterogeneous and is not composed simply of cases of AD with incidental stroke.     

Hippocampal size may contribute to prospective diagnosis of age-related dementia

Background: The hippocampus is a center of cognitive function and therefore hippocampal atrophy is the major factor in cognitive decline. Analysis of hippocampal size may make it possible to predict progression in cognitive impairment. To address this point, the present study investigated the relationship between hippocampal atrophy and dementia using magnetic resonance (MR) images and the Hasegawa Dementia Scale‐Revised (HDS‐R). Methods: The present study was performed on 274 subjects (14–97 years old; average, 66 years; 106 male and 168 female) who had no focal neurological deficit. Hippocampal area and whole brain area were measured in three series of coronal MR images taken from a 5‐mm slice rostrally along dorsal edge of the pons, and hippocampal size normalized by calculating summated hippocampal areas as percentages of summated whole brain areas. Dementia was screened for using HDS‐R. Results: Hippocampal size decreased and HDS‐R reduced with age. Hippocampal atrophy was highly correlated with cognitive deterioration; a critical normalized hippocampal size for HDS‐R of less than 20, which corresponds with mild cognitive impairment and dementia, was found in 65% of over 60‐years old subjects and 98% of subjects with HDS‐R of less than 20 were over 60 years old. Conclusion: There is a high probability that over 60‐year‐old people with a normalized hippocampal size of less than 1.0 would develop dementia in the future, even though their HDS‐R might presently be over 20. Measurement of hippocampal size with coronal MR imaging may therefore contribute to prospective diagnoses of age‐related dementia.     

Rates of cognitive decline in Alzheimer's disease and dementia with Lewy bodies

Increased interest in types of dementia has developed as more cases are identified in aging populations. Here we compare the rates of cognitive decline over time in three groups with dementia from the University of Western Ontario Dementia Study: Alzheimer's disease (AD), dementia with Lewy bodies and a group with both AD and Lewy bodies. All diagnoses were verified by autopsy using standard diagnostic methods. Cognitive impairment was measured with the Extended Scale for Dementia (ESD). Members of each group with dementia were age and sex matched with individuals without dementia as controls. The 15 cases of AD, 7 cases with Lewy bodies and 8 cases with both conditions were all free of significant vascular disease. Linear regression was used to determine the rate of changes in ESD scores over time in months. All three control groups showed no change in cognitive status over time. As expected, all groups with dementia showed progressive cognitive impairment. Analysis of the slope parameter showed that all groups deteriorated at the same rate of approximately 2 ESD points per month. Quadratic models fit better than simple linear models in all groups. Results suggest that the final rate of cognitive decline in dementia may not necessarily reflect the underlying cause.     

CASCADE: a European collaborative study on vascular determinants of brain lesions. Study design and objectives

Dementia is a highly prevalent disease that may have a cardiovascular component. White matter lesions and brain atrophy (brain abnormalities) are prevalent in dementia cases and might form part of the anatomical basis for the disease. We designed a multi-centre study, CASCADE (Cardiovascular Determinants of Dementia), to examine long-term (10-20 years) and short-term (5 years) cardiovascular risk factors for, and the cognitive consequence of, brain abnormalities. White matter lesions and atrophy are measured with magnetic resonance imaging. Cognitive function is measured with nine tests of memory and executive function. The studies included in CASCADE were ongoing and geographically spread throughout Europe to capture the cardiovascular risk gradient. In each study, a random sample of at least 100 subjects aged 65-75 years was selected who participated in the previous research examinations conducted by the respective centres. The objectives and design of the CASCADE project are described.     

Multiple sclerosis

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that commonly leads to inflammatory and atrophic brain pathology, often causing cognitive impairment. MS-associated cognitive impairment was first described over a century ago. However, with the advent of standardized neuropsychological testing and quantitative brain imaging, the frequency, quality, and correlates of cognitive impairment are better understood. Dementia is rare in MS, although it is known to occur in 10 to 25% of patients. Our data suggest a frequency of 22% among clinic attendees. In addition to the cognitive impairments evident in MS dementia, changes in personality and social behavior also occur. For example, some patients develop euphoria sclerotica and marked deficiency in social empathy, conditions that in combination with executive dysfunction cause considerable hardship for patients and caregivers. These neuropsychiatric manifestations of MS dementia are correlated with magnetic resonance imaging indicators of brain atrophy, including ventricle enlargement, neocortical volume, and normalized whole brain volume. Recent developments in pharmacological treatment for disease progression and management of cognitive symptoms hold promise for patients suffering from the degenerative aspects of MS.     

Clinical determinants of dementia and mild cognitive impairment following ischaemic stroke: the Sydney Stroke Study

BACKGROUND: Dementia following stroke is common but its determinants are still incompletely understood. METHODS: In the Sydney Stroke Study, we performed detailed neuropsychological and medical-psychiatric assessments on 169 patients aged 50-85 years, 3-6 months after a stroke, and 103 controls with a majority of both groups undergoing MRI brain scans. Stroke subjects were diagnosed as having vascular mild cognitive impairment (VaMCI) or vascular dementia (VaD) or no cognitive impairment by consensus. Demographic, functional, cerebrovascular risk factors and neuroimaging parameters were examined as determinants of dementia using planned logistic regression. RESULTS: 21.3% of subjects were diagnosed with VaD, with one case in those aged 50-59 years, 24% in those aged 60-69 years and 23% in those 70-79 years. There was no difference by sex. The prevalence of VaMCI was 36.7%. VaD subjects had lower premorbid intellectual functioning and had 0.9 years less education than controls. The VaD and VaMCI groups did not differ from the no cognitive impairment group on any specific cerebrovascular risk factor, however overall those with impairment had a greater number of risk factors. They did not differ consistently on depression severity, homocysteine levels and neuroimaging parameters (atrophy, infarct volume and number of infarcts) except for an excess of white matter lesions on MRI and greater number of infarcts in the VaD and VaMCI groups. On a series of logistic regression analyses, stroke volume and premorbid function were significant determinants of cognitive impairment in stroke patients. CONCLUSION: Post-stroke dementia and MCI are common, especially in older individuals. Cerebrovascular risk factors are not independent risk factors for VaD, but stroke volume is a significant determinant of dementia. Premorbid functioning is a determinant of post- stroke impairment.     

Cerebral white matter changes and rate of progression of dementia during cholinesterase inhibitor treatment: a retrospective cohort study

BACKGROUND: Cerebral white matter changes (WMC) represent cerebrovascular disease (CVD) and are common in dementia. Cholinesterase inhibitors (ChEIs) are effective in Alzheimer's Disease (AD) with or without CVD, and in Dementia with Lewy Bodies (DLB). Predictors of treatment response are controversial. OBJECTIVE: To investigate the effect of WMC severity on rate of progression of dementia during treatment with ChEIs. METHODS: CT or MRI brain scans were rated for WMC severity in 243 patients taking ChEIs for dementia. Raters were blind to patients' clinical risk factors, dementia subtype and course of illness. Effects of WMC severity on rates of decline in cognition, function and behaviour were analysed for 140 patients treated for 9 months or longer. Analysis was performed for this group as a whole and within diagnostic subgroups AD and DLB. The main outcome measure was rate of change in Mini Mental State Examination (MMSE) score. Secondary measures were rates of change in scores on the Cambridge Cognitive Examination (CAMCOG), Instrumental Activities of Daily Living (IADL) and Clifton Assessment Procedures for the Elderly - Behaviour Rating Scale (CAPE-BRS). RESULTS: There was no significant association between severity of WMC and any specified outcome variable for the cohort as a whole or for patients with AD. In patients with DLB, higher WMC scores were associated with more rapid cognitive decline. CONCLUSIONS: Increased WMC severity does not influence clinical response to ChEI treatment in AD, but may hasten deterioration in ChEI-treated patients with DLB.     

Ventricular dilatation and brain atrophy in patients with Parkinson's disease with incipient dementia

Age‐related ventricular enlargement is accelerated in Alzheimer's disease, but its relationship to cognitive decline in Parkinson's disease is less clear, even though dementia is common in Parkinson's disease. Our goals were to determine if greater enlargement of the ventricles and gray or white matter atrophy occurred in Parkinson's disease patients developing cognitive decline. Older nondemented patients with Parkinson's disease (33) and age‐ and sex‐matched controls (39) were recruited and prospectively assessed for the development of significant cognitive decline over 36 months. Magnetic resonance imaging was obtained every 18 months, and ventricular volume and total brain gray and white matter volumes were measured using reliable segmentation of T1‐weighted volumetric scans. Subjects with incidental intracranial abnormalities, an atypical course, and stroke as well as dropouts were excluded from a cohort of 52 patients and 50 controls. Among 33 patients and 39 controls, 10 patients and 3 controls developed significant cognitive impairment or dementia. Ventricular change and Parkinson's disease status were significantly associated with dementia. Ventricular change was significantly correlated with change in Mini‐Mental Status Examination in the Parkinson's disease with dementia group (r = 0.87, P = .001). Gray matter atrophy was greater in Parkinson's disease with dementia, with similar change over time in both Parkinson's disease and Parkinson's disease with dementia. White matter volumes were not significantly different between Parkinson's disease and Parkinson's disease with dementia; however, the decrease over time might be greater in Parkinson's disease with dementia. Ventricular dilatation occurs early in the course of significant cognitive decline in patients with Parkinson's disease, possibly reflecting both cortical gray and white matter loss. © 2011 Movement Disorder Society     

Performance on the Mattis Dementia Rating Scale in patients with vascular dementia: relationships to neuroimaging findings

Impairment on screening measures such as the Mattis Dementia Rating Scale (MDRS) provides evidence of dementia in patients with cerebrovascular disease. However, the relationships between neuroimaging findings and performance on the MDRS in vascular dementia (VD) have not been determined. In the present study, we examined the relationships between subcortical hyperintensity (SH) volume and whole brain volume (WBV) on the subscales and total score of the MDRS. Results revealed that SH accounted for a significant amount of variance on the Initiation/Perseveration and Construction subscales, whereas WBV accounted for a significant amount of variance on the Memory subscale. The total score on the MDRS was found to be significantly related to WBV but not SH. These results suggest that subcortical damage and brain volume account for different aspects of cognitive decline in VD and that overall cognitive impairment may reflect cortical and subcortical involvement.     

Vascular cognitive impairment

Cognitive impairment commonly accompanies clinical syndromes associated with vascular disease of the brain. Because of evolving definitional criteria, however, the frequency of cognitive impairment attributable to cerebrovascular disease is difficult to determine. Dementia occurs in up to one-third of elderly patients with stroke, a subset of whom have Alzheimer's disease (AD) rather than a pure vascular dementia syndrome. In fact, pure vascular dementia has been shown to be uncommon in most large autopsy series. A mixed etiology of AD and cerebrovascular disease is thought to become more common with increasing age, although no clinical criteria for the diagnosis of AD with cerebrovascular disease are currently available. Epidemiological studies have implicated subcortical small-vessel disease as a risk factor for cognitive impairment and dementia, but the cognitive expression and clinical significance of MRI white matter changes in individual patients is difficult to establish. The frequency of specific neuropathologic features of vascular cognitive impairment depends largely on study inclusion criteria. Cerebral meningocortical microangiopathies with distinctive clinicopathological profiles are associated with dementia in both sporadic cases and familial syndromes. In patients with AD, the contribution of amyloid-beta protein to the degree of cognitive impairment has not been clearly defined.     

Does the hippocampal atrophy correlate with the cortical theta power in elderly subjects with a range of cognitive impairment?

A previous study with a small sample (N = 39) showed a significant correlation between the cortical theta activity and the hippocampal volume in different stages of cognitive impairment in aged subjects. The recent study was aimed to replicate these results in a much bigger sample. The authors examined a sample of 121 right-handed subjects. The sample consisted of 37 healthy controls, 40 patients with questionable dementia, and 44 patients with mild dementia assessed by Clinical Dementia Rating. All subjects underwent EEG and brain MRI. Mean spectral power was calculated, and volume of hippocampal segments was measured. EEG theta power of the left and right hemisphere correlated significantly with the hippocampal volume on the left and right side in different stages of cognitive impairment. An increase of theta power was associated with decreased hippocampal volume. No other significant correlations were found for alpha or beta band power. No correlation was found between cortical theta and global brain volume. There seems to be a direct relationship between neuronal loss of the hippocampus and changed cortical theta activity for different stages of cognitive impairment in aged subjects.     

Longitudinal magnetic resonance imaging vascular changes, apolipoprotein E genotype, and development of dementia in the neurocognitive outcomes of depression in the elderly study.

OBJECTIVE: Several studies suggest that depression is a risk factor for development of dementia in the elderly. In a study of older depressed individuals, the authors examined both neuroimaging and genetic factors in development of dementia. The authors hypothesized that change in subcortical gray matter and white matter hyperintensity volumes would be associated with development of dementia, as would presence of an apolipoprotein E (APOE) epsilon 4 allele. METHODS: The sample consisted of 161 older depressed subjects without dementia who had magnetic resonance imaging scans at baseline and at two years. Blood samples were also taken to determine APOE genotype. All participants were treated with antidepressants using a guideline-based treatment algorithm. Their cognitive status was evaluated annually. A consensus panel of experts evaluated each case to determine cognitive status and assign a diagnosis. RESULTS: Twenty subjects became demented over the follow-up period (5.4 years on average). Change in white matter hyperintensity volume was significantly associated with development of dementia, especially among non-Alzheimer dementias. There was a trend for change in subcortical gray matter hyperintensity volume to be associated with incident dementia. APOE genotype was not associated with onset of dementia. CONCLUSION: Worsening cerebrovascular disease in older depressed adults is associated with cognitive decline and dementia, particularly of the non-Alzheimer disease type. The association of change in white matter lesion volume and incident dementia among depressed elders extends the vascular depression hypothesis of geriatric depression to include cognitive outcomes of depression in the elderly.     

Hippocampal and cortical atrophy predict dementia in subcortical ischemic vascular disease

BACKGROUND: The cause of dementia in subcortical ischemic vascular disease (SIVD) is controversial. OBJECTIVES: To determine whether cognitive impairment in SIVD 1) correlates with measures of ischemic brain injury or brain atrophy, and/or 2) is due to concomitant AD. METHODS: Volumetric MRI of the brain was performed in 1) elderly subjects with lacunes (L) and a spectrum of cognitive impairment-normal cognition (NC+L, n = 32), mild cognitive impairment (CI+L, n = 26), and dementia (D+L, n = 29); 2) a comparison group with probable AD (n = 28); and 3) a control group with normal cognition and no lacunes (NC). The authors examined the relationship between the severity of cognitive impairment and 1) volume, number, and location of lacunes; 2) volume of white matter signal hyperintensities (WMSH); and 3) measures of brain atrophy (i. e., hippocampal, cortical gray matter, and CSF volumes). RESULTS: Among the three lacune groups, severity of cognitive impairment correlated with atrophy of the hippocampus and cortical gray matter, but not with any lacune measure. Although hippocampal atrophy was the best predictor of severity of cognitive impairment, there was evidence for a second, partially independent, atrophic process associated with ventricular dilation, cortical gray matter atrophy, and increase in WMSH. Eight autopsied SIVD cases showed variable severity of ischemic and neurofibrillary degeneration in the hippocampus, but no significant AD pathology in neocortex. The probable AD group gave evidence of only one atrophic process, reflected in the severity of hippocampal atrophy. Comparison of regional neocortical gray matter volumes showed sparing of the primary motor and visual cortices in the probable AD group, but relatively uniform atrophy in the D+L group. CONCLUSIONS: Dementia in SIVD, as in AD, correlates best with hippocampal and cortical atrophy, rather than any measure of lacunes. In SIVD, unlike AD, there is evidence for partial independence between these two atrophic processes. Hippocampal atrophy may result from a mixture of ischemic and degenerative pathologies. The cause of diffuse cortical atrophy is not known, but may be partially indexed by the severity of WMSH.     

Progression of white matter hyperintensities in Alzheimer disease, dementia with lewy bodies, and Parkinson disease dementia: a comparison with normal aging.

OBJECTIVE: The objective of this study was to investigate cross-sectional and longitudinal white matter hyperintensity (WMH) changes in older subjects with clinically diagnosed dementia. METHODS: Fluid-attenuated inversion recovery images were acquired one year apart in subjects with dementia with Lewy bodies (DLB), Parkinson disease dementia (PDD), Alzheimer disease (AD), and also healthy elderly comparison subjects. WMH volume was quantified using an automated technique. RESULTS: Baseline WMH (as a percent of brain volume) was significantly greater compared with healthy subjects (N=33, geometric mean WMH: 0.4%) in subjects with AD (N=23 [1.3%], analysis of variance post hoc p <0.001) but not PDD (N=13 [0.6%]) or DLB (N=14 [0.4%]). Increase in WMH volume (as a percent of brain volume) was not significantly different (Kruskal-Wallis p=0.4) between groups (AD median change: 0.08%; DLB: 0.025%; PDD: 0.07%, healthy: 0.02%). Severity of baseline WMH, rather than diagnosis or severity of dementia, was a significant predictor of lesion progression. Rate of change of WMH had no association with change in global cognitive performance. CONCLUSIONS: Significant WMH progression occurs in degenerative dementias with rates influenced by severity of lesions at baseline rather than dementia type or cognitive decline.     

Brain structure and cognition in a community sample of elderly Latinos

BACKGROUND: Previous studies have found that hippocampal atrophy and white matter hyperintensities (WMH) on MRI are linked to cognitive impairment and dementia. The authors measured these variables in a population-based cohort of older Mexican Americans with a wide spectrum of cognitive ability, ranging from normal cognition to dementia. OBJECTIVE: To investigate whether these structural brain changes were seen in individuals prior to the development of dementia and how these changes were related to the presence of dementia. METHODS: A sample of 122 subjects was selected from the Sacramento Area Latino Study on Aging, and subjects were categorized into four groups of increasing levels of cognitive impairment: normal, memory impaired (MI), cognitively impaired but not demented (CIND), and demented. Hippocampal volume was quantified using a region of interest approach. WMH was rated on a semiquantitative scale as the percent of total volume of white matter. RESULTS: Hippocampal volume was significantly reduced in CIND and demented individuals, and WMH were significantly increased in demented subjects. MI subjects did not have any significant changes in hippocampal volume or WMH. The risk for developing dementia was significantly and comparably increased in subjects with either hippocampal atrophy or high WMH. However, the risk for dementia increased dramatically in subjects with both hippocampal atrophy and a high degree of WMH. CONCLUSION: Reductions in hippocampal volume may be present before dementia but not until cognitive impairment is relatively severe. Because there is a synergistic effect between high WMH and hippocampal atrophy, interactions between vascular and degenerative processes may be important determinants of dementia.     

Inheritance of the ApoE epsilon4 allele increases the rate of brain atrophy in dementia patients.

We investigated the influence of the apolipoprotein (ApoE) epsilon4 allele on the rate of brain atrophy in patients with clinical dementia and in subjects at risk for dementia. Eighty-one subjects, consecutively referred to a memory clinic due to symptoms of dementia, went through a comprehensive examination, including cerebral magnetic resonance imaging. After an initial investigation these subjects were divided into one of six diagnostic groups; Alzheimer's disease (AD, n = 23), objective cognitive impairment (OCI, n = 27), subjective cognitive impairment (SCI, n = 17), vascular dementia (VaD), frontotemporal dementia (FTD) and unspecified dementia (USD). The last three groups were joined into one diagnostic group designated 'other dementia' (OD, altogether n = 14). In order to study the progression of cognitive impairment as well as the rate of atrophy in different brain regions all subjects were reinvestigated after an average period of 16 months. Interest was focused on investigating if those subjects with one or two epsilon4 alleles differed in either dementia progression or rate of brain atrophy compared to those without the epsilon4 allele. We found that the ApoE epsilon4 carriers had a statistically significantly larger increase in ventricular volume as compared with the ApoE epsilon4 noncarriers. In all diagnostic groups the ApoE epsilon4 carriers showed a greater rate of ventricular volume increase, as compared to the noncarriers. However, this difference was statistically significant only for the OD subjects. No statistical significant changes over time were seen for whole brain volume or volume of the temporal lobes and the medial temporal lobes. The diagnostic groups differed in dementia progression with the AD subjects having the most pronounced reduction in MMSE scores as compared to subjects at risk for AD (OCI and SCI subjects). The presence of ApoE epsilon4 allele did not influence the change in MMSE in any of the diagnostic groups.     

Cognitive and functional resilience despite molecular evidence of Alzheimer’s disease pathology

BackgroundThe correlation between neuropathological lesions and cognition is modest. Some individuals remain cognitively intact despite the presence of significant Alzheimer’s disease (AD) pathology, whereas others manifest cognitive symptoms and dementia in the same context. The aim of the present study was to examine cognitive and cerebral reserve factors associated with resilient functioning in the setting of AD pathology.MethodsUniversity of Pennsylvania Alzheimer’s Disease Center research participants with biochemical biomarker evidence of AD pathology (cerebrospinal fluid amyloid-β_1-42 <192 pg/mL) and comparable medial temporal lobe atrophy were categorized by Clinical Dementia Rating Scale-Sum of Boxes (CDR-SOB) score as AD dementia (CDR-SOB >1) or AD resilient (CDR-SOB ≤0.5). Groups were compared for a variety of demographic, clinical, and neuroimaging variables to identify factors that are associated with resilience to AD pathology.ResultsA univariate model identified education and intracranial volume (ICV) as significant covariates. In a multivariate model with backward selection procedure, ICV was retained as a factor most significantly associated with resilience. The interaction term between ICV and education was not significant, suggesting that larger cranial vault size is associated with resilience even in the absence of more education.ConclusionsPremorbid brain volume, as measured through ICV, provided protection against clinical manifestations of dementia despite evidence of significant accumulations of AD pathology. This finding provides support for the brain reserve hypothesis of resilience to AD.     

MRI volumes of the hippocampus and amygdala in adults with Down's syndrome with and without dementia

OBJECTIVE: This study sought to determine whether volumes of the hippocampus and amygdala are disproportionately smaller in subjects with Down's syndrome than in normal comparison subjects and whether volume reduction is greater in Down's syndrome subjects with dementia. METHOD: The subjects were 25 adults with Down's syndrome (eight with dementia) and 25 cognitively normal adults who were individually matched on age, sex, and race. Magnetic resonance imaging measures included volumes of the hippocampus, amygdala, and total brain. Nineteen of the Down's syndrome subjects had follow-up scans (interscan interval = 9-41 months). RESULTS: Nondemented Down's syndrome subjects had significantly smaller volumes of the hippocampus, but not the amygdala, than their comparison subjects, even when total brain volume was controlled for. Volumes of both the hippocampus and the amygdala were smaller in the demented Down's syndrome subjects than in their comparison subjects, even when total brain volume was controlled for. Age was not correlated with volume of the hippocampus or amygdala among the nondemented Down's syndrome subjects and the comparison subjects; age was correlated with volume of the amygdala, but not the hippocampus, among the Down's syndrome subjects with dementia. Changes in volume over time were not statistically significant for either the demented or the nondemented subjects. CONCLUSIONS: Hippocampal volume, while disproportionately small for brain size in individuals with Down's syndrome, remains fairly constant through the fifth decade of life in those without dementia. All subjects over age 50 who had Down's syndrome demonstrated volume reduction in the hippocampus as well as clinical signs of dementia. Dementia was also associated with volume reductions in the amygdala that exceeded reductions in total brain volume.     

Asynchronous regional brain volume losses in presymptomatic to moderate AD

To determine if rates and locations of brain volume loss associated with AD are phase-specific, occurring prior to clinical onset and at later stages, we performed longitudinal volumetric MRI analysis on 155 subjects enrolled in a prospective study of aging and dementia. Subjects were divided by Clinical Dementia Rating (CDR) scale into stages of Normal (CDR 0 --> 0), Very Mild (CDR 0 --> 0.5 and 0.5 --> 0.5), Mild (CDR 0.5 --> 1.0 and 1.0 --> 1.0) and Moderate (CDR 1.0 --> 2.0 and 2.0 --> 2.0) dementia. Rates of volume change in CSF spaces, lobar and medial temporal lobe regions were analyzed for group differences across stages. Annual rates of ventricular volume change differed between non-demented and very mild group (p<0.01). In later severity stages, ventricular, temporal, basal ganglia-thalamic region and total volumes show change. Rates of volume loss increase as dementia progresses, but not uniformly in all regions. These regional and phase-specific volume changes form targets for monitoring disease-modifying therapies at clinically relevant, defined stages of dementia.