Objective: To establish the progression of brain atrophy rates in patients wit h a known date of onset of Alzheimer disease (AD).Methods: Each of 18 subjects h ad two high-resolution T1-weighted three-dimensional MRI ...Objective: To establish the progression of brain atrophy rates in patients wit h a known date of onset of Alzheimer disease (AD).Methods: Each of 18 subjects h ad two high-resolution T1-weighted three-dimensional MRI examinations. The tw o MRIs were coregistered and the annual rate of brain tissue atrophy was derived both for the entire brain and regionally for the left and right medial temporal lobe (MTL). Time since onset (TSO) of AD, defined as the interval between the d ate of onset and the midpoint of MRI dates, ranged from -2.9 to 4.2 years. Resu lts:In patients with AD, TSO was a correlate of the atrophy rate for both the le ft MTL (R2 = 0.58, p = 0.001) and right MTL (R2 = 0.30, p = 0.03). When serial m easurements were applied to a control group of 21 cognitively normal elderly sub jects,MTL atrophy rate classified the group membership (AD vs normal cognition) with an accuracy of 92.3%. Conclusion:Increased annual atrophy rate in the medi al temporal lobe is a potential diagnostic marker of the progression of Alzheime r disease.展开更多
The main unifying feature of cases with frontotemporal dementia (FTD) is the p attern of brain atrophy. Surprisingly, there are a variety of underlying histopa thologies in cases with the clinical features and typical...The main unifying feature of cases with frontotemporal dementia (FTD) is the p attern of brain atrophy. Surprisingly, there are a variety of underlying histopa thologies in cases with the clinical features and typical pattern of atrophy cha racterizing FTD. This suggests that the degenerative mechanism(s) associated wit h pyramidal cell loss and gliosis in FTD is likely to be similar in the differen t histopathological forms of the disease. In this study we tested this hypothesi s by analysing a common cell death mechanism, apoptosis, in cases of FTD with ei ther Picks disease (PiD) (n = 9) or frontotemporal lobar degeneration (FTLD) ( n = 7) compared with normal controls (n = 10). Tissue sections from previously a nalysed cases were stained using anti activated caspase-3 immunohistochemistry , TUNEL, propidium iodide, and cell and pathology specific labels. These marke rs of apoptosis identified both astrocytes and neurons in regions vulnerable to degeneration in all cases of FTD. However, neuronal apoptosis was rare (<2 %of neurons), even at early disease stages where there is considerably less fro ntotemporal atrophy or pyramidal cell loss. This suggests that other cell death mechanisms account for the progressive neuronal loss in FTD. In contrast, astroc ytes with beaded processes and other apoptotic features were very frequent in bo th PiD and FTLD, with the severity of astrocytosis and astrocytic apoptosis corr elating with both the degree of neuronal loss and the stage of disease. These fi ndings provide evidence that astrocytic apoptosis occurs as an early event in di fferent histopathological forms of FTD. Furthermore, this astrocytic apoptosis d irectly relates to the degree of degeneration in FTD, and becomes the overwhelmi ng pathological feature as the disease progresses.展开更多
文摘Objective: To establish the progression of brain atrophy rates in patients wit h a known date of onset of Alzheimer disease (AD).Methods: Each of 18 subjects h ad two high-resolution T1-weighted three-dimensional MRI examinations. The tw o MRIs were coregistered and the annual rate of brain tissue atrophy was derived both for the entire brain and regionally for the left and right medial temporal lobe (MTL). Time since onset (TSO) of AD, defined as the interval between the d ate of onset and the midpoint of MRI dates, ranged from -2.9 to 4.2 years. Resu lts:In patients with AD, TSO was a correlate of the atrophy rate for both the le ft MTL (R2 = 0.58, p = 0.001) and right MTL (R2 = 0.30, p = 0.03). When serial m easurements were applied to a control group of 21 cognitively normal elderly sub jects,MTL atrophy rate classified the group membership (AD vs normal cognition) with an accuracy of 92.3%. Conclusion:Increased annual atrophy rate in the medi al temporal lobe is a potential diagnostic marker of the progression of Alzheime r disease.
文摘The main unifying feature of cases with frontotemporal dementia (FTD) is the p attern of brain atrophy. Surprisingly, there are a variety of underlying histopa thologies in cases with the clinical features and typical pattern of atrophy cha racterizing FTD. This suggests that the degenerative mechanism(s) associated wit h pyramidal cell loss and gliosis in FTD is likely to be similar in the differen t histopathological forms of the disease. In this study we tested this hypothesi s by analysing a common cell death mechanism, apoptosis, in cases of FTD with ei ther Picks disease (PiD) (n = 9) or frontotemporal lobar degeneration (FTLD) ( n = 7) compared with normal controls (n = 10). Tissue sections from previously a nalysed cases were stained using anti activated caspase-3 immunohistochemistry , TUNEL, propidium iodide, and cell and pathology specific labels. These marke rs of apoptosis identified both astrocytes and neurons in regions vulnerable to degeneration in all cases of FTD. However, neuronal apoptosis was rare (<2 %of neurons), even at early disease stages where there is considerably less fro ntotemporal atrophy or pyramidal cell loss. This suggests that other cell death mechanisms account for the progressive neuronal loss in FTD. In contrast, astroc ytes with beaded processes and other apoptotic features were very frequent in bo th PiD and FTLD, with the severity of astrocytosis and astrocytic apoptosis corr elating with both the degree of neuronal loss and the stage of disease. These fi ndings provide evidence that astrocytic apoptosis occurs as an early event in di fferent histopathological forms of FTD. Furthermore, this astrocytic apoptosis d irectly relates to the degree of degeneration in FTD, and becomes the overwhelmi ng pathological feature as the disease progresses.
