Alzheimer's disease markers, hypertension, and gray matter damage in normal elderly
Lidia GlodzikLisa MosconiWai TsuiSusan De SantiRaymond ZinkowskiElizabeth PirragliaKenneth RichPauline McHughYi LiSteven WilliamsFahad AliHenrik ZetterbergKaj BlennowPankaj MehtaMony J. de Leon
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Statistical parametric mapping
Frontal lobe
The authors performed quantitation of the temporal lobes using magnetic resonance imaging in 20 patients with mild‐tomoderate Alzheimer's disease, 20 age‐matched aged control subjects, and 26 healthy young volunteers. Compared to young subjects, aged controls showed volume reductions in amygdala (17%, p =0.02), hippocampus (15%, p =0.0001) and temporal lobe (22%, p =0.0001). Compared to aged controls, Alzheimer's subjects showed further volume reductions in amygdala (33%, p =0.0001) and hippocampus (20%, p =0.006) but not temporal lobe (7%, p =0.15). In Alzheimer's subjects, left temporal lobe volume correlated strongly with the Mini Mental State (MMSE) score (adjusted r 2 =0.46, p =0.0006) whereas right amygdala volume correlated inversely with the noncognitive ADAS score (adjusted r 2 =0.46, p =0.0006). The authors conclude that significant volume changes occur in the temporal lobe in aging and in Alzheimer's disease, with the greatest percentage reductions in the amygdala in Alzheimer's disease. Temporal neocortical atrophy and temporal limbic atrophy might be associated with different patterns of performance and behavior in Alzheimer's patients.
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This study examined regional cerebral blood flow (rCBF) in Alzheimer's disease (AD) patients with and without subclinical hypothyroidism (SCH).Eleven AD patients with SCH and 141 AD patients without SCH underwent brain perfusion single photon emission computed tomography (SPECT). The SPECT data were analyzed by statistical parametric mapping (SPM8) and FineSRT.AD patients with SCH showed a significantly decreased rCBF mainly in the temporal lobe and thalamus, whereas those without SCH showed a significantly decreased rCBF in the parietotemporal lobe and cingulate gyrus as well as the frontal lobe.Our findings suggest that SCH may affect cerebral perfusion in regions associated with the memory function.
Statistical parametric mapping
Subclinical infection
Frontal lobe
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Diagnosis of Alzheimer''s disease is made on clinical grounds, and the availability of a simple and sensitive quantitative index of the disease might aid in the routine diagnosis. The aim of this study was to assess whether linear measures of brain atrophy as detected by magnetic resonance imaging can be helpful in the differentiation of mild to moderate Alzheimer''s disease from nondemented elderly. Measures of global (bifrontal index and interuncal distance) and hippocampal (minimum thickness of the medial temporal lobe, hippocampal height, width of the choroid fissure, and width of the temporal horn) atrophy were taken from 26 cases and 21 controls. Measures of hippocampal atrophy were the most sensitive in the differentiation of cases from controls, and among them width of the temporal horn yielded the highest sensitivity, predicting the disease in 73% of cases with 95% specificity. A compound measure comprising width of the temporal horn, width of the choroid fissure, and hippocampal height increased sensitivity to 85%. These results suggest that selected simple indices of hippocampal atrophy might be useful in the diagnosis of Alzheimer''s disease.
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Objective: To establish the progression of brain atrophy rates in patients with a known date of onset of Alzheimer disease (AD). Methods: Each of 18 subjects had two high-resolution T1-weighted three-dimensional MRI examinations. The two 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 date of onset and the midpoint of MRI dates, ranged from −2.9 to 4.2 years. Results: In patients with AD, TSO was a correlate of the atrophy rate for both the left MTL (R2 = 0.58, p = 0.001) and right MTL (R2 = 0.30, p = 0.03). When serial measurements were applied to a control group of 21 cognitively normal elderly subjects, MTL atrophy rate classified the group membership (AD vs normal cognition) with an accuracy of 92.3%. Conclusion: Increased annual atrophy rate in the medial temporal lobe is a potential diagnostic marker of the progression of Alzheimer disease.
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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).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.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.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.
Frontal lobe
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This study compared rates of regional atrophy in Alzheimer disease (AD), frontotemporal dementia (FTD), and semantic dementia (SD). Cross-sectional studies have shown that different dementia syndromes are associated with different patterns of regional brain tissue loss. Rates of atrophy over time may be useful for differential diagnosis, and could be used to monitor disease progression, serving as an outcome measure for clinical trials. We studied patients with AD (n=12), FTD (n=13), SD (n=20), and normal controls (n=23) longitudinally with structural magnetic resonance imaging, using BRAINS2 software to measure frontal, temporal, and parietal lobe volumes. In FTD the rate of frontal lobe atrophy over 1 year was greater than in any other group, whereas SD showed the highest rate in the temporal lobes. Atrophy in these regions progressed twice as quickly in FTD and SD compared with AD. Atrophy was not significantly faster for AD in any brain region compared with the other groups. Regional atrophy over time was significantly faster in FTD and SD compared with AD, and the regions of greatest atrophy were specific for each syndrome. Measuring specific regions of cerebral volume changes by serial neuroimaging may serve as a useful biomarker outcome measure for clinical trials in neurodegenerative diseases.
Frontotemporal lobar degeneration
Semantic dementia
Frontal lobe
Cerebral atrophy
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The association between cerebrospinal fluid (CSF) and serum concentration of thyroid hormones and pituitary thyrotropin stimulating hormone (TSH) was studied in nine hypothyroid patients (HT) before and in seven after L-thyroxine treatment. With L-thyroxine, median free T4 increased 4-fold in serum (3.5 pmol/L vs 17.5 pmol/L) and 3-fold in CSF, (3.9pmol/L vs 11.5 pmol/L). Correspondingly, total T3 in serum increased two-fold (0.9 nmol/L vs 2.2 nmol/L). Unexpectedly, free T3 concentration in CSF was similar (1.5 pmol/L vs.1.5 pmol/L) before and during treatment. In HT, TSH in serum correlated with TSH in CSF as did free T4 in serum and in CSF. During L-thyroxine, the correlation with TSH in serum and CSF remained. Likewise, the free T4 concentration in serum correlated with that in CSF. However, no correlation was found between T3 in serum and free T3 in CSF. It seems evident that free T4 in serum equilibrates with that in the CSF both in the HT and during L-thyroxine. Despite a two-fold increase in total serum T3, free T3 in CSF remained unchanged, which agrees with previous results in rats showing that T3 is less exchangeable between serum and CSF. Alternatively, an accelerated conversion of T4 to T3 might have maintained the concentration of T3, due to strongly increased levels of TSH found in the hypothyroid state. The notion that free T4 in serum reflects the CSF concentration of free T4 is consistent with previous reports from studies in animals.
Free thyroxine
Serum concentration
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Objective To study the feature of regional cerebral metabolism rate of glucose (rCMRglc) in patients with Alzheimer’s disease (AD) and the value of positron emission tomography (PET) scanning in diagnosis of AD. Methods 13 AD patients and 13 health controls ,Who matched in age,sex and education years,were scanned with PET. Results (1) Watching by naked eyes,there was mild decreasing of rCMRglc at parietal lobe in healthy elders. While in AD patients,there was widely decreasing of cerebral metabolism rate of glucose. The most significant region was parietal lobe, the next was temporal lobe,and the last was frontal lobe. (2) Detecting with PET and dealing with statistical parametric mapping (SPM) of 99 software,there was more significant decreasing of rCMRglc in regions 7,23,30,31 of cingulate gyrus,region 39 and 40 of pario-occipital lobe,region 20 of temporal lobe and region 6,8,9 of frontal lobe in AD group( P 0.05,0.01). There was a larger rCMRglc decreasing area in the left cerebral hemisphere than that in the right. Conclusions There is universal decreasing of rCMRglc in AD. There is a significant decreasing of rCMRglc in some regions. These regions' dysfunction may induce symptoms of AD,such as cognitive impairment,personality change,behavior and psychological symptoms of AD patients. Decreasing of rCMRglc in some brain regions can be considered as one of the evidences in the diagnosis of AD.
Statistical parametric mapping
Frontal lobe
Parietal lobe
Posterior cingulate
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Computed tomographic scans in the temporal lobe orientation are a valuable way of studying the medial temporal lobe. In patients with histopathologically-confirmed Alzheimer's disease the size of the medial temporal lobe is almost half that in age-matched controls and the rate of atrophy shown by yearly scans (15% per year) is 10-fold greater. Such a rapid rate of atrophy probably follows a catastrophic event in the brain indicating that Alzheimer's disease is distinct from accelerated normal ageing. The degree of medial temporal lobe atrophy is related to the density of neurofibrillary tangles in the hippocampus; it is a useful guide to diagnosis and has potential as a screening tool in populations. It is proposed that measurement of the rate of atrophy in asymptomatic individuals may be a predictor of Alzheimer's disease and could be used to monitor the effectiveness of therapies designed to retard the rate of neurodegeneration.
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