Comprehensive dissection of the medial temporal lobe in AD: measurement of hippocampus, amygdala, entorhinal, perirhinal and parahippocampal cortices using MRI

Background Early pathological involvement of specific medial temporal lobe areas is characteristic for Alzheimer’s disease (AD). Objective To determine the extent of regional medial temporal lobe atrophy, including hippocampus, amygdala, and entorhinal, perirhinal, and parahippocampal cortices in mild AD patients and healthy controls, and to compare diagnostic accuracy across volumetric markers. Methods We studied 34 patients with clinically probable AD and 22 healthy elderly control subjects. Regional volumetric measures were obtained from volumetric T1–weighted MRI scans after accounting for global brain atrophy using affine transformation into standard space. Results Volumes of medial temporal lobe structures were significantly smaller in AD patients than in controls with exception of the left entorhinal cortex. The degree of atrophy was comparable between all structures. Diagnostic accuracy (number of correctly allocated cases divided by number of all cases) was highest for the right parahippocampal cortex with 85%, but only slightly lower for the right hippocampus and right entorhinal cortex with 82% and 84%. Using a linear combination of markers, the unilateral volumes of the right hippocampus, parahippocampal cortex and perirhinal cortex yielded an accuracy of 93%. Conclusion Extent of atrophy is similar between the different regions of the medial temporal lobe in mild AD.Volume measurements of medial temporal lobe structures in addition to the hippocampus only yield improved diagnostic accuracy if a combination of these structures is used.     

A comparison of medial and lateral temporal lobe atrophy in dementia with Lewy bodies and Alzheimer's disease: magnetic resonance imaging volumetric study

OBJECTIVES: To compare medial and lateral temporal lobe atrophy on magnetic resonance imaging (MRI) in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), and to examine the relationship between volumetric indices and cognitive and non-cognitive symptoms. METHODS: T(1)-weighted 1.0-tesla MRI scans were acquired in elderly subjects with DLB (n = 26; mean age = 75.8 years) and AD (n = 22; 77.3 years) and normal controls (n = 26; 76.2 years). MRI-based volume measurements of the hippocampus, parahippocampus, fusiform gyrus, combined inferior and middle temporal gyri, and superior temporal gyrus were acquired. RESULTS: Hippocampal and parahippocampal volumes were significantly larger in subjects with DLB compared to AD. Differences in hippocampal volumes between DLB and AD were observed across the entire length, and in all subjects with dementia there was a loss of hippocampal asymmetry compared to normal controls. Atrophy of temporal lobe structures correlated with memory impairment in both groups, and with age in DLB. There was no association between atrophy and psychotic symptoms in either group. CONCLUSIONS: Subjects with DLB and AD have a different pattern of temporal lobe atrophy with the most striking differences relating to medial rather than lateral temporal lobe structures. These structural differences could explain the relative preservation of memory function in DLB compared to AD.     

Selective reduction of N-acetylaspartate in medial temporal and parietal lobes in AD

BACKGROUND: Both AD and normal aging cause brain atrophy, limiting the ability of MRI to distinguish between AD and age-related brain tissue loss. MRS imaging (MRSI) measures the neuronal marker N-acetylaspartate (NAA), which could help assess brain change in AD and aging. OBJECTIVES: To determine the effects of AD on concentrations of NAA, and choline- and creatine-containing compounds in different brain regions and to assess the extent NAA in combination with volume measurements by MRI improves discrimination between AD patients and cognitively normal subjects. METHODS: Fifty-six patients with AD (mean age: 75.6 +/- 8.0 years) and 54 cognitively normal subjects (mean age: 74.3 +/- 8.1 years) were studied using MRSI and MRI. RESULTS: NAA concentration was less in patients with AD compared with healthy subjects by 21% (p < 0.0001) in the medial temporal lobe and by 13% to 18% (p < 0.003) in parietal lobe gray matter (GM), but was not changed significantly in white matter and frontal lobe GM. In addition to lower NAA, AD patients had 29% smaller hippocampi and 11% less cortical GM than healthy subjects. Classification of AD and healthy subjects increased significantly from 89% accuracy using hippocampal volume alone to 95% accuracy using hippocampal volume and NAA together. CONCLUSION: In addition to brain atrophy, NAA reductions occur in regions that are predominantly impacted by AD pathology.     

Topographical patterns of lobar atrophy in frontotemporal dementia and Alzheimer's disease

BACKGROUND/AIMS: Fronto-temporal dementia (FTD) designates a group of relatively common neurodegenerative disorders. The aim of this study was to characterize the patterns of brain atrophy in FTD compared to Alzheimer's disease (AD). METHODS: A novel semiautomatic volumetric MRI analysis method was applied to measure regional brain volumes in FTD (n = 15; behavioural variant n = 9, language variant n = 6) in contrast with AD patients (n = 15) and age-matched controls (NC) (n = 15). FTD and AD patients were matched on demographic measures and Mini Mental State Examination scores. RESULTS: Significant atrophy was present in the frontal and anterior temporal lobes of subjects with FTD compared to AD (p = 0.02; effect size = 1.11) and compared to NC (p < 0.001; effect size = 1.86). Severe atrophy of the left anterior temporal region distinguished the language variant. AD patients, by contrast, did not differ from NC for frontal lobe volume but had smaller anterior temporal lobes (p = 0.03). Both dementia groups had medial temporal lobe atrophy of similar magnitude. A logistic regression model including 4 regional measures correctly classified 100% of subjects. CONCLUSION: FTD can be reliably differentiated from AD by virtue of a topographical pattern of atrophy involving the frontal lobes and anterior temporal regions. Medial temporal lobe volumes do not distinguish FTD from AD.     

A longitudinal study of brain volume changes in normal aging using serial registered magnetic resonance imaging

OBJECTIVE: To investigate the effect of age on global and regional brain volumes and rates of atrophy, and to compare directly results based on cross-sectional and longitudinal data. METHODS: Thirty-nine healthy control subjects (age range, 31-84 years) underwent serial magnetic resonance imaging assessments. Measurements included the whole-brain, temporal lobe, hippocampal, and ventricular volumes at baseline and for repeat scans. RESULTS: We found significant decreases in cross-sectional whole-brain (P<.001), temporal lobe (P<.001), and hippocampal (P =.003) volumes and a significant increase in ventricular volume (P<.001) with increasing age. Cross-sectional and longitudinal estimates of atrophy rates were similar. We also found directional evidence of acceleration in atrophy rates with increasing age in all analyses, with the most marked changes occurring after 70 years of age. This increase in rates after 70 years of age was particularly marked in the ventricles (P<.001) and the hippocampi (P =.01). CONCLUSIONS: We found a significant age-associated decrease in global and regional brain volumes. Some evidence indicates that this decline in brain volumes may be due to a nonlinear acceleration in rates of atrophy with increasing age. A better understanding of this process may help to discriminate normal age-related changes from neurodegenerative diseases.     

Focal Atrophy and Cerebrovascular Disease Increase Dementia Risk among Cognitively Normal Older Adults

BACKGROUND AND PURPOSE: This study investigated the association of medial temporal lobe (MTL) atrophy and cerebrovascular disease (white matter hyperintensities [WMH], subclinical infarcts) with the risk of developing Alzheimer's disease (AD) among cognitively normal older adults. METHODS: Risk of developing AD was examined for 155 cognitively normal older adults (77.4 years, 60% women, 81% white). The MTL volumes and the presence of WMH and of subclinical infarcts were determined from brain magnetic resonance imaging (MRI) at the beginning of the study. Follow-up cognitive evaluations (average 4.3 years) identified those who developed AD. RESULTS: The presence of either MTL atrophy or subclinical infarcts was independently and significantly associated with a greater risk to develop AD (OR [95% CI]: 4.4 [1.5, 12.3] and 2.7 [1.0, 7.1], respectively). In addition, those participants with both MTL atrophy and at least one brain infarct had a 7-fold increase in the risk of developing AD (OR [95% CI]: 7.0 [1.5, 33.1]), compared to those who had neither of these conditions. CONCLUSIONS: In cognitively normal older adults, markers of neurodegeneration (as reflected by MTL atrophy) and of cerebrovascular disease (as reflected by infarcts on MRI) independently contribute to the risk to develop AD.     

Does Alzheimer's disease affect hippocampal asymmetry? Evidence from a cross-sectional and longitudinal volumetric MRI study

OBJECTIVE: To determine whether Alzheimer's disease (AD) is associated with preferential atrophy of either the left or right hippocampus. METHODS: We examined right-left asymmetry in hippocampal volume and atrophy rates in 32 subjects with probable AD and 50 age-matched controls. Hippocampi were measured on two serial volumetric MRI scans using a technique that minimizes laterality bias. RESULTS: We found a non-significant trend for right > left (R > L) asymmetry in controls at both time points (R > L: 1.7%; CI: -0.3-3.7%; p = 0.1). AD subjects showed a similar non-significant trend for R > L asymmetry at baseline (R > L: 1.8%; CI: -1.9-5.5%; p = 0.32), but not at repeat (p = 0.739). Change in R/L ratio between visits in AD patients was significant (p = 0.02). The AD group had significantly higher variance in these ratios than the controls at baseline (p = 0.02), but not repeat (p = 0.06). AD patients had higher atrophy rates than controls (p < 0.001). Mean (CI) annualized atrophy rates for left and right hippocampi were 1.2% (0.5-1.8%) and 1.1% (0.5-1.8%) for the controls, and 4.6% (3.3-6.0%) and 6.3% (4.9-7.8%) for AD subjects. There was no significant asymmetry in atrophy rates in controls (p = 0.9), but borderline significantly higher atrophy rates in the right hippocampus of the AD group (p = 0.05) compared to the left. Presence of an APOEepsilon4 allele had no significant effect on the size, asymmetry or atrophy rates in AD (p > 0.20). CONCLUSIONS: We report minor R > L asymmetry in hippocampal volumes in controls and present some evidence to suggest that there is a change in the natural R > L asymmetry during the progression of AD.     

APOE-epsilon4 is associated with less frontal and more medial temporal lobe atrophy in AD

OBJECTIVE: To test the hypothesis that the e4 allele of APOE is associated with a region-specific pattern of brain atrophy in AD. METHODS: Volumes of the hippocampi, entorhinal cortices, and anterior temporal and frontal lobes were measured in 28 mild to moderate AD patients and 30 controls using MRI. Within the AD group, 14 patients were noncarriers (-/-), 9 were heterozygous (e4/-), and 5 were homozygous (e4/4) for the e4 allele. Dementia severity was similar across the three AD groups. RESULTS: Smaller volumes were found with increasing dose of the e4 allele in the hippocampus, entorhinal cortex, and anterior temporal lobes in AD patients. When compared with controls, the volume loss in the right and left temporal regions ranged from -15.3 to -22.7% in the -/- AD group, from -26.2 to -36.0% in the e4/- group, and from -24.0 to -48.0% in the e4/4 group (p < 0.0005). In contrast, larger volumes were found in the frontal lobes with increasing e4 gene dose. When compared with controls, volume differences of the right frontal lobe were -11.8% in the -/- AD group, -8.5 in the e4/- group, and -1.4% in the e4/4 group (p = 0.03). CONCLUSIONS: We found smaller volumes in the temporal lobe regions but larger volumes in the frontal lobes with increasing APOE-e4 gene dose in AD patients. These data suggest a region-specific biological effect of the e4 allele in the brains of AD patients.     

Blood pressure, white matter lesions and medial temporal lobe atrophy: closing the gap between vascular pathology and Alzheimer's disease?

BACKGROUND: Vascular factors are recognized as important risk factors for Alzheimer's disease, although it is unknown whether these factors directly lead to the typical degenerative pathology such as medial temporal lobe atrophy. We set out to investigate the relation between blood pressure and medial temporal lobe atrophy in patients with senile and presenile Alzheimer's disease with or without white matter lesions. METHODS: We determined the relation between blood pressure and pulse pressure and medial temporal lobe atrophy on MRI in 159 patients with Alzheimer's disease, stratified on white matter lesions and age at onset of dementia. RESULTS: There was a linear relation between systolic blood pressure and pulse pressure (both in tertiles) and the severity of medial temporal lobe atrophy (p(trend) = 0.05 and p(trend) 0.03, respectively). A significant relation was found between pulse pressure [beta = 0.08 (95% CI: 0.00-0.15; p = 0.05) per 10 mm Hg] and (borderline significant) systolic blood pressure [beta = 0.05 (95% CI: -0.01 to 0.11; p = 0.1) per 10 mm Hg] and medial temporal lobe atrophy. White matter lesions and age-stratified analysis revealed a significant association between systolic blood pressure and pulse pressure and medial temporal lobe atrophy, only in the subsample with white matter lesions and in the subsample with a senile onset of dementia. The relations were independent of severity of dementia and diabetes mellitus. CONCLUSIONS: Systolic blood pressure and pulse pressure are associated with medial temporal lobe atrophy in Alzheimer's disease, especially in the presence of white matter lesions and in patients with a late onset of dementia. Our finding may be another step in providing a rationale on how vascular factors could ultimately result in Alzheimer's disease.     

Magnetic resonance measures in Alzheimer disease: their utility in early diagnosis and evaluating disease progression.

We sought to identify the most reliable magnetic resonance (MR) measures for the diagnosis and staging of Alzheimer disease (AD) in a clinical setting and to estimate, for different degrees of dementia, the rate of change of cerebral atrophy in certain regions of interest (ROIs). Forty-two probable AD patients and eight normal controls underwent MR brain scans, neurological examinations, and neuropsychological testing. We computed each subject's corpus callosum width, ventricular size, right and left temporal lobe areas, interuncal distance, and assessed the degree of cortical atrophy. We also estimated the rate of change for Information-Memory-Concentration Test scores and for temporal lobe areas and corpus callosum width. Measures of temporal lobe area and subjective evaluation of temporal lobe atrophy both served to distinguish controls from mild AD cases (p < 0.05), whereas only the latter differentiated moderate from severe patients (p < 0.05). The rate of change for temporal lobe areas remained constant over different AD stages, whereas those for corpus callosum width and for cognitive impairment were greater for severe cases (p < 0.05). Our findings imply that measurements of temporal lobe area and ratings of temporoparietal atrophy can be useful in the diagnosis and staging of AD and suggest that atrophy progressed at different rates in selected ROIs for various stages of AD severity.     

MRI线性测量局部脑萎缩对早期阿尔兹海默病的诊断意义

目的评价ＭＲＩ线性测量脑萎缩程度对阿尔兹海默病（Ａｌｚｈｅｉｍｅｒｄｉｓｅａｓｅ，ＡＤ）患者的早期诊断价值。方法应用ＭＲＩ线性定量测量对３０例轻度痴呆的ＡＤ患者、２０例多发脑梗塞性痴呆（ＭＩＤ）和２０名正常老年人进行局部额叶（双额指数、额叶半球间宽度）、中颞叶（海马钩回间距、中颞叶最小厚度）及海马结构（海马高度、脉络膜裂宽度、海马脑干间距及颞角宽度）等指标测量。结果颞角宽度指标是区别ＡＤ患者与ＭＩＤ患者及正常老年人的最敏感的指标；其敏感性达９０％，特异性达８５％。如结合脉络膜裂宽度、海马高度、海马与脑干间距及海马钩回间距，其敏感性达９３％，特异性达９５％。结论ＭＲＩ线性定量测量局部海马萎缩能够作为早期诊断ＡＤ的准确可靠性指标之一。     

The Radial Width of the Temporal Horn in Mild Cognitive Impairment

BACKGROUND AND PURPOSE: The diagnosis of preclinical Alzheimer's disease (AD) (or mild cognitive impairment [MCI]) is loaded with a high degree of uncertainty. The aim was to test the accuracy of a computed tomography-based (CT-based) marker of medial temporal lobe atrophy, the radial width of the temporal horn (rWTH), in MCI. METHODS: Ten MCI and 42 AD patients and 29 nondemented controls underwent brain CT on the temporal lobe plane (slice thickness = 2 mm). The rWTH was taken on CT films with a precision caliper placed at the tip of the temporal horn radial to the curvature of the hippocampal head region. RESULTS: When specificity was fixed at 95%, the sensitivity for the detection of AD was 39/42 (93%) and that for the detection of MCI was 8/10 (80%). CONCLUSION: The rWTH is a measure sensitive to the regional brain atrophy common in early AD.     

Increased cortical atrophy in patients with Alzheimer's disease and type 2 diabetes mellitus

BACKGROUND: The risk of Alzheimer's disease (AD) is increased in type 2 diabetes (DM2). This increased risk has been attributed to vascular comorbidity, but other mechanisms, such as accelerated ageing of the brain, have also been implicated. OBJECTIVE: To determine whether AD in patients with DM2 is associated with an increased occurrence of vascular lesions in the brain, by increased cerebral atrophy, or a combination of both. METHODS: In total, 29 patients with AD and DM2 and 58 patients with AD and without DM2 were included in the study. Clinical characteristics were recorded, and a neuropsychological examination and magnetic resonance imaging (MRI) scan were performed. MRI scans were rated for cortical and subcortical atrophy, medial temporal lobe atrophy, white matter lesions, and infarcts. RESULTS: The neuropsychological profiles of the two groups were identical. Patients with AD and DM2 had increased cortical atrophy on MRI (p<0.05) compared with the non-DM2 group. In addition, infarcts were more common (odds ratio 2.4; 95% CI 0.8 to 7.8), but this effect did not account for the increased atrophy. The other MR measures did not differ between the groups. CONCLUSION: The results suggest that non-vascular mechanisms, leading to increased cortical atrophy, are also involved in the increased risk of AD in DM2.     

Fronto-temporal-lobe atrophy in early-stage Alzheimer's disease identified using an improved detection methodology

Alzheimer's disease (AD) is associated with widespread brain atrophy including structures subserving memory. We applied an improved structural detection methodology to examine the less well known progression of atrophy in early-stage AD. We sought to i) longitudinally study volumetric differences in patients with early-stage AD and healthy volunteers; and ii) test the hypothesis that hippocampal volumes would be correlated with clinically relevant cognitive function. Seven patients and eleven healthy subjects underwent two structural MRI scans and neuropsychological assessments. Scans were normalised to a study-specific template and 'morphologically opened' to reduce tissue misclassification. Using brain-parcellation, patient atrophy was localised to left fusiform and parahippocampal gyri, whilst left hippocampal volumes were correlated with a cognitive performance measure. A whole-brain search methodology, showed that patients had reduced volumes including fronto-temporal regions bilaterally, in hippocampi and amygdalae and right cerebellum. Whole-brain correlational analyses revealed that cognitive performance was correlated with volumes of both hippocampi, superior temporal gyri and left insula. Neither group exhibited significant longitudinal volumetric changes. Utilising a novel methodology, we have shown that in early-stage AD, clinically relevant cognitive deficits are correlated with regionally specific grey-matter volumes, which are detectable at an early stage of the illness.     

Quantitative MRI volume changes in late onset schizophrenia and Alzheimer''s disease compared to normal controls

Volumes of medial and lateral temporal lobe structures were assessed using magnetic resonance imaging (MRI) in 11 patients with late-life onset schizophrenia (LOS), 18 normal elderly controls and 12 patients with moderate cognitive impairment due to Alzheimer's disease (AD) who had no non-cognitive symptoms. While both patient groups has smaller volumes of several medial temporal regions (e.g. entorhinal cortex, left hippocampus), schizophrenics had significantly smaller anterior superior temporal gyri (STG) than normal controls, but AD patients did not. We have previously demonstrated anterior STG volume to be reduced in early life onset schizophrenia.     

Combining short interval MRI in Alzheimer’s disease

Cerebral atrophy calculated from serial MRI is a marker of Alzheimer’s disease (AD) progression, and a potential outcome measure for therapeutic trials. Reducing within-subject variability in cerebral atrophy rates by acquiring more than two serial scans could allow for shorter clinical trials requiring smaller patient numbers. Forty-six patients with AD and 23 controls each had up to 10 serial MR brain scans over two years. Whole brain atrophy was calculated for each subject from every scan-pair. 708 volumetric MRI scans were acquired: 2199 measures of atrophy were made for patients, and 1182 for controls. A linear mixed model was used to characterise between and within-individual variability. These results were used to investigate the power of combining multiple serial scans in treatment trials of varying lengths. In AD, the mean whole brain atrophy rate was 2.23%/year (95% CI: 1.90–2.56%/year). The linear mixed model was shown to fit the data well and led to a formula (0.99²+(0.82/t)²) for the variance of atrophy rates calculated from two scans “t” years apart. Utilising five optimally timed scans with repeat scans at each visit reduced the component of atrophy rate variance attributable to within-subject variability by ~ 56%, equating to a ~ 40% sample size reduction (228 vs 387 patients per arm to detect 20% reduction in atrophy rate) in a six-month placebo-controlled trial. This benefit in terms of sample size is relatively reduced in longer trials, although adding extra scanning visits may have benefits when patient drop-outs are accounted for. We conclude that sample sizes required in short interval therapeutic trials using cerebral atrophy as an outcome measure may be reduced if multiple serial MRI is performed     

Progressive cerebral atrophy in MS: a serial study using registered, volumetric MRI

OBJECTIVE: To assess the potential of registered volumetric MRI in measuring rates of atrophy in MS. BACKGROUND: Pathologic and imaging studies suggest that the development of permanent neurologic impairment in MS is associated with progressive brain and spinal cord atrophy. Atrophy has been suggested as a potential marker of disease progression. Conventional atrophy measurements requiring manual outlining are time-consuming and subject to reproducibility problems. Registration of serial MRI may offer a useful alternative in that cerebral losses may be measured directly from automated subtraction of brain volumes. METHODS: Twenty-six patients with MS and 26 age- and gender-matched controls had two volumetric brain MR studies 1 year apart. Baseline brain and ventricular volumes were measured using semiautomated techniques, and follow-up scans were registered to baseline. Rates of cerebral atrophy were calculated directly from the registered scans. RESULTS: Baseline brain volumes in the MS group were smaller (mean difference 78 mL [95% CI 13 to 143; p = 0.02]) and ventricular volumes greater (mean difference 12 mL [95% CI 6 to 18; p < 0.001]) than controls. The rate of cerebral atrophy in the MS group (0.8% per year) was over twice that of controls (0.3%), and the rate of ventricular enlargement was five times greater than the controls (1.6 versus 0.3 mL/year). CONCLUSION: Progressive cerebral atrophy is an important feature of MS. Registration-based measurements are sensitive and reproducible, allowing progressive atrophy to be detected within 1 year and may have potential as a marker of progression in monitoring therapeutic trials.     

Medial temporal lobe atrophy in memory disorders

Medial temporal lobe atrophy determined by temporal lobe oriented computed tomography (CT), 1 year before death, is strongly associated with histopathologically confirmed Alzheimer’s disease (AD). The aim of this study was to assess the diagnostic accuracy of medial temporal lobe measurement for the diagnosis of AD in patients referred to a memory disorders clinic, especially those at an early stage of the disease. CT oriented to the temporal lobe was performed in 333 subjects aged 41–93 years consecutively recruited in a Memory Disorders Clinic: 124 had probable AD, Mini Mental State score (MMS) = 17 (8); 50 possible AD [MMS = 21 (5)]; and 119 patients had miscellaneous memory disorders [MMS = 22 (7): frontotemporal lobe dementia, subcortical dementia, cortical Lewy body disease, vascular dementia, Korsakoff syndrome, focal atrophy, etc.]. There were also 19 anxious/ depressed patients [MMS = 29 (1)] with normal performance on memory tests, and 21 controls. The minimum width of the medial temporal lobe was measured. The best cut-off to distinguish AD patients from non-AD patients was 11.5 mm, in agreement with data in the literature. At this threshold, 84% of probable AD patients had a positive test and 90% of controls and anxious/depressed patients had a negative test. For the diagnosis of probable AD, sensitivity of the measurement was 0.81, specificity 0.95, predictive positive value 0.99, predictive negative value 0.45, and diagnostic accuracy 0.83. The test was positive in half the possible AD patients, and half those with miscellaneous memory disorders. It was negative in all anxious/depressed patients. Therefore, temporal lobe oriented CT might be a valuable tool for assessment of medial temporal lobe atrophy in AD routine practice. Received: 27 September 1995 Accepted: 10 October 1996     

Reduced temporal lobe volume in early onset conduct disorder

Regional brain volumes derived from magnetic resonance imaging (MRI) scans from 10 youths with early onset conduct disorder and 10 healthy controls matched for age, sex and handedness were compared to determine whether prefrontal or temporal lobe brain volumes differed in the two groups. Right temporal lobe and right temporal gray matter volumes were significantly reduced in subjects with conduct disorder compared with controls. Prefrontal volumes in subjects with conduct disorder were 16% smaller than in controls, but the difference did not reach statistical significance. Early onset conduct disorder without substance abuse comorbidity was also significantly associated with smaller right temporal gray volumes. Further investigation of both the temporal and frontal localizations of the pathophysiology of early onset conduct disorder is warranted in larger samples.     

The progression of Alzheimer's disease from limbic regions to the neocortex: clinical, radiological and pathological relationships

Alzheimer's disease (AD) is characterised by the gradual accumulation of neurofibrillary pathology in selected regions of the brain. Earlier studies indicate that the accumulation of neurofibrillary tangles is associated both with decline in patient's cognitive performance as well as with medial temporal lobe atrophy on CT scans. There are also indications that progression through the pathological stages of AD is associated with decline in cognitive functions. The results of this study indicate that progression of disease, especially beyond the boundaries of the limbic regions, is associated with marked decline in the cognitive performance of patients suffering from AD. However the clinical manifestations of early pathological stages are not so well defined. We also found that the atrophy of the medial temporal lobe on CT scans is related to the progression of pathology. Atrophy is most apparent when the disease reaches its isocortical stages and is not marked in the limbic stages of the disease. The additive effect of pathologies co-existing with AD is apparent in reduced cognitive scores, while the atrophy of limbic structures, as measured on CT scans, seems to be mainly attributable to AD-related pathology.