Lobar distribution of changes in gray matter and white matter in memory clinic patients: detected using magnetization transfer imaging.

BACKGROUND AND PURPOSE: Previous studies have shown involvement of both gray matter (GM) and white matter (WM) in mild cognitive impairment (MCI) and Alzheimer disease (AD). In this study, we assessed the lobar distribution of the GM and WM pathology over the brain and the association of lobar distribution with global cognitive decline. MATERIALS AND METHODS: Fifty-five patients with AD, 19 patients with MCI, and 43 subjects with normal cognitive function participated in this study. GM and WM were segmented on dual fast spin-echo and fluid-attenuated inversion recovery MR images. A custom template representing anatomic areas was applied. Magnetization transfer imaging (MTI) peak height and mean magnetization transfer ratio (MTR) provided measures for structural brain damage. RESULTS: Both mean MTR and MTI peak height showed that patients with AD had more structural brain damage in the GM of all lobes compared with controls. Patients with MCI had lower GM peak height compared with controls for the temporal and frontal lobe. WM peak height was lower for all lobes investigated for patients with both AD and MCI. WM mean MTR was lower in the frontal, parietal, and temporal lobes for patients with AD compared with controls. Age and both temporal GM peak height and mean MTR were the only parameters that predicted cognition. CONCLUSION: This study shows that in addition to more focal GM MTI changes in the temporal and frontal lobes, widespread WM changes are present in the earliest stages of AD. This might point to an important role for WM pathology in the earliest stage of AD.

[Three patients with autoimmune hepatitis: the importance of early diagnosis and remission]. / Drie vrouwen met auto-immune hepatitis: het klinisch belang van tijdige diagnose en van remissie.

A 70-year-old woman presented with impaired memory and depressive symptoms and two women aged 53 and 30 years, respectively, presented with general malaise and fatigue. All were diagnosed with and treated for autoimmune hepatitis (AIH). The first patient developed a relapse during treatment withdrawal; she recovered and maintained remission after the initial dose of medication had been restarted and the medication was tapered more gradually. The second patient had an incomplete remission and later developed liver failure; she was eligible for a liver transplant. The third woman became pregnant during treatment and developed a relapse after delivery; remission was induced and maintained after the immunosuppression was temporally increased. AIH is a chronic progressive liver disease characterised by abnormal serum levels of liver enzymes, hypergammaglobulinaemia, auto-antibodies against cell nuclei (ANA), smooth muscle (SMA), or liver and kidney microsomes (LKM), interface hepatitis and the absence of other chronic liver disease. Early diagnosis is essential because therapy can markedly improve prognosis. However, there is no specific diagnostic test for AIH. It is important to induce and maintain remission with immunosuppressive therapy.

Cognitive decline in AD and mild cognitive impairment is associated with global brain damage.

OBJECTIVE: To investigate the relationships between structural damage in the whole brain, the temporal lobes, and the frontal lobes and cognitive decline at old age. The authors hypothesized that widespread brain damage as quantified using magnetization transfer imaging (MTI) is related to global cognitive decline, whereas regional damage to the temporal lobes is related to memory impairment, and regional damage to the frontal lobes is related to executive dysfunctioning. METHODS: Cognitive function of 22 patients with probable AD, 13 patients with mild cognitive impairment (MCI), and 28 elderly controls was assessed using an extensive neuropsychological test battery. Structural damage in the whole brain, the temporal lobes, and the frontal lobes was estimated using volumetric MTI analysis. Associations between MTI measures and neuropsychological tests were investigated using Pearson correlation analysis. RESULTS: MTI measures of the whole brain, as well as the temporal and the frontal lobes, were strongly associated with global cognitive deterioration and impairment in memory, orientation, language, praxis, gnosis, and executive functioning. However, there were no specific cognitive correlates of regional brain damage to the temporal and frontal lobes. CONCLUSIONS: Using whole brain volumetric magnetization transfer imaging, the authors demonstrated that cognitive decline in patients with mild cognitive impairment and AD is associated with widespread structural brain damage. As there were no specific relationships between regional brain damage and impairment of specific cognitive functions, pathology in AD and mild cognitive impairment is much more generalized than was expected.

Magnetization transfer imaging of gray and white matter in mild cognitive impairment and Alzheimer's disease.

OBJECTIVE: To assess whether structural brain damage as detected by magnetization transfer imaging (MTI) in Alzheimer's disease (AD) and mild cognitive impairment (MCI) is located in the gray matter (GM) and/or the white matter (WM). METHODS: Fifty-five AD patients, 19 MCI patients and 43 subjects with normal cognitive function participated in this study. GM and WM segmentations were generated from dual fast spin-echo MR images. These masks were co-registrated to MT images for volumetric MTI-analysis of the GM and WM. RESULTS: AD patients had a lower GM volume than controls. Both MCI and AD patients had more structural brain damage in both GM and WM than subjects with normal cognition. Cerebral lesion load in both GM and WM was associated with the degree of cognitive impairment. CONCLUSION: Using MTI, structural brain changes that are related to cognitive impairment could be demonstrated in both GM and WM of patients with AD and MCI. These results suggest that cerebral changes are present in GM and WM even before patients are clinically demented.

Effect of atorvastatin on impaired vascular function in healthy old men.

OBJECTIVE: This study was initiated to examine the effect of cholesterol-lowering therapy with 40 mg atorvastatin on vascular function in healthy old and young men. METHODS: We selected healthy normolipidaemic, elderly subjects (n = 8, mean age 80.1 years) and young subjects (n = 7, mean age 21.8 years). All had a normal electrocardiograph and blood pressure, and signs or symptoms of cardiovascular disease were absent. The subjects were studied for 2 days, with 6 weeks of atorvastatin treatment in between. Forearm blood flow (FBF) was measured by computerized venous occlusion plethysmography upon intra-arterial infusion of acetylcholine (ACh; 30 and 90 ng/kg/min) and 5-hydroxytryptamine (5-HT; 0.3 and 0.9 ng/kg/min) as endothelium-dependent vasodilators, and sodium nitroprusside (SNP; 30 and 90 ng/kg/min) as an endothelium-independent vasodilator. RESULTS: At baseline, the mean absolute FBF in the elderly was 2.6 mL/min/100 mL and in the young 4.3 mL/min/100 mL tissue (P = 0.01). The mean serum total cholesterol levels were 5.2 and 3.8 mmol/L, respectively (P = 0.007). The endothelium-dependent vasodilatation induced by ACh and 5-HT was significantly lower in the elderly compared with the young (both P < 0.01), whereas the endothelium-independent vasodilatation induced by SNP was not significantly lower in the elderly compared with the young. Atorvastatin treatment decreased the serum total cholesterol level with a mean of 38 and 28% in the elderly and the young, respectively (P < 0.001). Impaired endothelium-dependent vasodilatation, however, was not modified (P > 0.65). CONCLUSIONS: Healthy old men have an impaired endothelium-dependent vascular response but this impairment is not restored by treatment with atorvastatin.

Interaction of medial temporal lobe atrophy and white matter hyperintensities in AD.

The authors investigated the interaction between medial temporal lobe (MTL) atrophy and white matter hyperintensities (WMH) in Alzheimer disease (AD). They measured the MTL and WMH on MRI in 58 AD patients and 28 controls. MTL atrophy was associated with an increased risk of AD (OR = 6.2), but there was no significant association between WMH and AD. Moreover, there was an interaction between MTL and WMH (p = 0.045). These results suggest that vascular and Alzheimer-type pathology act in synergy in the clinical syndrome of AD.