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PubMed2006

A family with X-linked optic atrophy linked to the OPA2 locus Xp11.4-Xp11.2.

Autosomal dominant optic atrophy (ADOA) is the most common inherited optic atrophy. Clinical features of ADOA include a slowly progressive bilateral loss of visual acuity, constriction of peripheral visual fields, central scotomas, and color vision abnormalities. Although ADOA is the most commonly inherited optic atrophy, autosomal recessive, X-linked, mitochondrial, and sporadic forms have also been reported. Four families with X-linked optic atrophy (XLOA) were previously described. One family was subsequently linked to Xp11.4-Xp11.2 (OPA2). This investigation studied one multi-generation family with an apparently X-linked form of optic atrophy and compared their clinical characteristics with those of the previously described families, and determined whether this family was linked to the same genetic locus. Fifteen individuals in a three-generation Idaho family underwent complete eye examination, color vision testing, automated perimetry, and fundus photography. Polymorphic markers were used to genotype each individual and to determine linkage. Visual acuities ranged from 20/30 to 20/100. All affected subjects had significant optic nerve pallor. Obligate female carriers were clinically unaffected. Preliminary linkage analysis (LOD score = 1.8) revealed that the disease gene localized to the OPA2 locus on Xp11.4-Xp11.2. Four forms of inherited optic neuropathy, ADOA, autosomal recessive optic atrophy (Costeff Syndrome), Leber hereditary optic neuropathy, and Charcot-Marie-Tooth disease with optic atrophy, are associated with mitochondrial dysfunction. Future identification of the XLOA gene will reveal whether this form of optic atrophy is also associated with a mitochondrial defect. Identification of the XLOA gene will advance our understanding of the inherited optic neuropathies and perhaps suggest treatments for these diseases. An improved understanding of inherited optic neuropathies may in turn advance our understanding of acquired optic nerve diseases, such as glaucoma and ischemic optic neuropathy.

Chromosomes, Human, X↗

PubMed1992

Muscle atrophy continues after early cast removal following tendon repair.

We studied soleus (SOL), plantaris (PLN), and gastrocnemius (GST) muscles to determine whether early cast removal minimizes muscle atrophy or permits recovery from atrophy after tendon repair. After right tendocalcaneus (Achilles tendon) was transected and repaired, rabbit right hindlimbs were immobilized with the ankle plantar flexed and the knee flexed to 90 degrees. Rabbits were maintained in the cast and sacrificed at 5, 15, or 21 days postoperatively or the cast was removed on day 5 and the animals sacrificed at day 15 or 21. SOL, PLN, and GST muscles of both limbs were removed and weighed, and then histochemical analyses were performed on SOL and PLN muscles. Immobilization decreased SOL muscle wet weights, mean fiber cross-sectional area, and percentage of Type I fibers and increased the percentage of Type IIc fibers. Ten days after cast removal (i.e., postoperative day 15), SOL muscle atrophy and fiber composition did not differ significantly from continuously immobilized controls. However, 16 days after cast removal (i.e., postoperative day 21), SOL muscle fiber cross-sectional area and fiber composition were near normal, differing significantly from continuously casted controls. At each of the time intervals studied, PLN (containing many glycolytic fibers) did not atrophy as much as SOL (containing mainly oxidative fibers). Our results indicate that 1) early cast removal prevents atrophy of PLN glycolytic fibers, but not oxidative fibers in either PLN or SOL, and 2) early cast removal promotes recovery from atrophy of both oxidative and glycolytic fibers. In spite of the many differences between rabbits and humans, these findings suggest that, although early cast removal may not prevent oxidative muscle fiber atrophy after postoperative immobilization, it may facilitate recovery from atrophy.

Achilles Tendon↗

PubMed2006

Magnetic resonance imaging measures of brain atrophy in multiple sclerosis.

Magnetic resonance imaging (MRI) has been widely used to diagnose and monitor multiple sclerosis (MS). Although MRI-visible lesions are a key feature of MS, they are thought to correlate poorly with clinical progression. Neurodegeneration is increasingly being recognized as an important factor in the pathogenesis of MS, and MRI measures of brain atrophy have been suggested as surrogate markers of neuroaxonal loss and disease progression. This pathology may be more relevant to the progression of disability than focal inflammation. A number of MRI-based methods have been developed for the measurement of global and regional brain atrophy. Natural-history studies of MS and clinically isolated syndromes suggestive of MS have observed atrophy in these subjects above that seen in controls, over periods ranging from three months to years. Brain atrophy has also been incorporated as an outcome measure in therapeutic trials of disease-modifying treatments. This paper considers neuroaxonal loss and the pathological basis of brain atrophy, methods developed to quantify brain atrophy, the findings of natural-history and therapeutic studies, the relationship of brain atrophy to disability and cognition, and the future research directions and clinical applications of brain atrophy measurements.

Atrophy↗

PubMed1998

Regional specificity of brain atrophy in Huntington's disease.

The present study analyzes the relationship between cortical and subcortical brain volumes in patients with Huntington's disease. The brains of seven patients with a clinical diagnosis and positive family history of Huntington's disease and 12 controls were collected at autopsy with consent from relatives. Detailed clinical assessments were available for all study subjects with genotype confirmation for patients with Huntington's disease. Volume analysis of the brain on serial 3-mm coronal slices was performed as previously described. All patients with Huntington's disease exhibited significant brain atrophy resulting from volume reductions in both cortical and subcortical grey matter. Atrophy of the cortex was relatively uniform, although the medial temporal lobe structures were spared. The caudate nucleus and putamen were strikingly reduced in all cases and this atrophy correlated with the severity of cortical atrophy, suggesting an associated disease process. The rate of cortical but not subcortical atrophy correlated with CAG repeat numbers. Loss of frontal white matter correlated with both cortical and striatal atrophy. Age of onset of chorea correlated with the amount of subcortical atrophy, while duration of chorea correlated negatively with atrophy of the white matter. These results suggest a more widespread and global disease process in patients with Huntington's disease.

Adult↗

PubMed2000

The relationship between fMRI activation and cerebral atrophy: comparison of normal aging and alzheimer disease.

Functional MRI has recently been used to examine activation associated with aging and dementia, yet little is known regarding the effect of cerebral atrophy on fMRI signal. The purpose of this study was to examine the relationship between measures of global and regionally specific atrophy and fMRI activation in normal aging and in Alzheimer disease (AD). Two groups of subjects were studied with echoplanar imaging and quantitative structural volumetry: healthy controls spanning a broad age and atrophy range (n = 16) and patients with mild AD (n = 8). Results from a semantic task previously found to activate left inferior frontal (LIFG) and left superior temporal (LSTG) gyri were analyzed. The correlations between clusters of activation in the LIFG and LSTG and measures of local atrophy in the LIFG and LSTG regions were evaluated. For control subjects, there was no significant correlation between activation and regional or total brain atrophy (for LIFG r = -0.03, NS; for LSTG r = 0.20, NS). In contrast, for AD patients, there was a significant positive correlation between atrophy and activation in LIFG (r = 0.70, P = 0.05) but not LSTG (r = 0.00, NS). These results suggest that activation of language regions and atrophy within those regions may be independent among healthy adults spanning a broad age and atrophy range. However, in AD, a relationship exists in the LIFG that may reflect compensatory recruitment of cortical units or disease-specific changes in the hemodynamic response.

Adult↗

PubMed1998

Overexpression of the anti-apoptotic oncogene, bcl-2, in the thymus does not prevent thymic atrophy induced by estradiol or 2,3,7, 8-tetrachlorodibenzo-p-dioxin.

Dexamethasone (Dex), estradiol (E2), and 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) all affect the immune system, causing immunosuppression and thymic atrophy. It is still uncertain how and where these compounds act to induce thymic atrophy. However, it has been suggested that these compounds may have similar actions and targets, i.e., apoptosis of immature thymocytes for Dex and TCDD and preferential targeting of double-positive cells by Dex and E2. The lckpr-bcl-2 transgenic mouse has been shown to be protected against Dex-induced thymic atrophy. We used this murine model to determine if bcl-2 expression would also protect against E2- and TCDD-induced thymic atrophy. Our results indicate that, although the bcl-2 transgenic (TG+) mice were fully protected from atrophy induced by a single dose of Dex, atrophy was still induced in these mice following treatment with E2 or TCDD. Phenotypic analysis of thymocytes from TG- and TG+ mice also showed distinct consequences of atrophy induced by Dex, E2, and TCDD. Finally, since there are alternative pathways for apoptosis that are bcl-2 independent, both TG- and TG+ thymocytes were examined directly for indications of apoptosis using the TUNEL assay. After TCDD and E2 treatment there were no detectable signs of apoptosis in either TG- or TG+ mice even at early time points and at elevated dose levels. These results indicate that there are distinct mechanisms for the actions of Dex, E2, and TCDD in the thymus and that apoptosis is not a key mechanism of E2- and TCDD-induced thymic atrophy.

Animals↗

PubMed2000

gamma-diketone peripheral neuropathy. I. Quality morphometric analyses of axonal atrophy and swelling.

Quantitative morphometric analysis was used to characterize expression of myelinated axon swelling and atrophy in rat peripheral nerve during 2,5-hexanedione (HD) intoxication. HD was administered by gavage according to different daily dosing regiments (100, 175, 250, or 400 mg/kg/day) and four proximodistal nerve regions (5th lumbar spinal nerve, proximal and distal sciatic nerve, and tibial nerve) were examined morphometrically. Morphometric determinations were made at four behavioral endpoints (unaffected, slight, moderate, and severe toxicity) and were correlated to electrophysiologic measurements of peripheral nerve function. Results show that, for all HD dose rates, onsets of behavioral neurotoxicity and nerve dysfunction were generally related to development of abundant axon atrophy. The proximodistal manifestation of atrophy was dependent upon the dosing rate; i.e., the atrophy response produced by subacute intoxication with higher daily dosing rates (250 and 400 mg/kg/day) was restricted to distal nerve regions whereas subchronic induction with lower dosing rates (100 and 175 mg/kg/day) produced abundant fiber atrophy in all proximodistal areas. In contrast to atrophy, axonal swellings constituted an inconsistent minor morphologic response, the expression of which was dependent upon subchronic dosing rates (100-250 mg/kg/day). Subacute HD administration (400 mg/kg/day) produced significant changes in neurobehavior and nerve electrophysiologic parameters in the absence of peripheral axon swelling. Thus, conditional expression of swellings suggests they are an epiphenomenon related to low-dose induction rates. Fiber atrophy, however, was numerically dominant, correlated with nerve dysfunction, and occurred at all dosing levels. These characteristics suggest atrophy is a neurotoxicologically significant feature of gamma-diketone peripheral neuropathy.

Animals↗

PubMed1988

Visual rehabilitation of patients with advanced stages of glaucoma, optic atrophy, myopia or retinitis pigmentosa.

Ninety-six patients with advanced stages of glaucoma, optic atrophy, myopia or retinitis pigmentosa (RP) who could not manage with ordinary spectacles or simple magnifying aids were taken care of at the Low Vision Clinic for rehabilitation and followed for an average of 3.6 years (the glaucoma group) up to an average of 6.0 years (the optic atrophy group). They were given high power optical aids and subjected to educational training in the proper use of these aids for best utilization of residual vision. Many of them (for optic atrophy as high a percentage as 40.7) were taught to use extra macular retina by means of eccentric viewing technique. The mean age of the oldest group, the glaucoma patients, was 69.3 years. The three other groups were about 20 to 25 years younger, on an average. (Another 35 patients were seen for the first series of visits but could not be followed up, the main reasons being death (13 patients) and moving out of the area (9 patients). The mean power of the aids (mainly telescopes) used for distance vision was 2.1 x (RP)-5.3 x (optic atrophy). Increased near addition and hyperocular lenses were the main aids for reading and near vision, the mean power being 17.0 dioptres (glaucoma)-23.5 dioptres (RP)(4.3 x -5.9 x). Aids were also provided for intermediate distance and for "spot use". The mean number of series of visits was 3.1 (myopia)-3.5 (glaucoma) and the average number of 1 h training sessions 2.2 (glaucoma)-2.5 (optic atrophy, RP) per series of visits. With aids and educational training, the mean visual acuity improved on the first series of visits from 0.31 to 0.60 for the glaucoma group, from 0.19 to 0.70 for the optic atrophy group, from 0.12 to 0.68 for the myopes and from 0.35 to 0.52 for the RP group. After the last series of visits acuity was still as good as 0.51, 0.61, 0.73 and 0.45, respectively. The number of individuals able to read newspaper text increased from 16.1% to 100.0% for the glaucoma patients, from 14.8% to 100.0% for the optic atrophy patients, from 75.0% to 100.0% for the myopes, and from 50.0% to 95.5% for the RP patients. The results show clearly that the methods used for rehabilitation of patients with glaucoma, optic atrophy, myopia or RP through optical aids and sessions of educational training are very successful, with substantial improvement of life quality.

Adolescent↗

PubMed1998

A study of sternocleidomastoid muscular atrophy after modified neck dissection.

To elucidate the conditions of atrophy in the sternocleidomastoid muscle (SCM) after modified neck dissection (MND), we tried to scrutinize the atrophic regions in the SCM and determine the cause of atrophy, by electromyography in 40 patients with SCM atrophy following MND. We also examined the detailed anatomy of the SCM in 40 cadavers. Atrophy was observed in the caudal portion in the SCM in 90% of the patients. Electromyographic examination revealed neurogenic atrophy in 24 patients, ischemic atrophy in 11, and a mixing of both types in 5. The SCM was found to be innervated by the spinal accessory nerve (SAN) and the SCM branch of the cervical nerve. The main artery feeding the cranial half of the SCM was a branch of the occipital artery (Oc) or the external carotid artery (Ex), and the auxiliary artery was a branch of the posterior auricular artery (Ap). The main artery feeding the caudal half of the SCM was a branch of the superior thyroidal artery (St), and the auxiliary artery was a branch of the subclavian artery (Sc). Postoperative SCM atrophy is attributed to damage of the feeding artery in the SCM caudal portion and local damage in the nerve fibers running through the SCM. To prevent this type of atrophy, it is important to carefully handle this muscle itself and protect the nerve fibers running through it, as well as to conserve the SCM branches of the St and Sc.

Aged↗

PubMed2002

Monitoring disease activity and progression in primary progressive multiple sclerosis using MRI: sub-voxel registration to identify lesion changes and to detect cerebral atrophy.

OBJECTIVE: To explore the potential usefulness of two new magnetic resonance imaging (MRI) analysis techniques for assessment of progressive cerebral atrophy and T2 lesion activity in primary progressive multiple sclerosis (PPMS), and thereby assess the relationship between MRI activity and atrophy in this patient group. BACKGROUND: Measurements of cerebral atrophy and net change in T2 lesion volumes are currently used as surrogate markers of disease progression in multiple sclerosis (MS). However, manual implementation of these techniques is time-consuming and the pathological specificity of T2 lesion change is low. Advances in serial scan registration have facilitated the development of a new, fully-automated technique to measure cerebral volume (SIENA; Structural Image Evaluation, using Normalisation, of Atrophy), and a technique to measure the total new T2 lesion volume selectively (MRI difference imaging). METHOD: SIENA measures changes in cerebral size based on sub-voxel detection of shifts in edge contours. The lesion difference imaging method measures differences in lesion volumes over time as defined by a semi-automated outlining technique. The two new methods were validated against the T2 lesion volume contour technique and a previously described measure of partial brain volume (which uses six slices centred on the presumed area of greatest change around the lateral ventricles). All were applied to serially acquired MR images from a cohort of 39 patients with PPMS, who also underwent scoring on the expanded disability status scale (EDSS) twice, two years apart. RESULTS: The two measures reflecting cerebral atrophy correlated strongly (r = 0.58, p < 0.001). T2 lesion load measurements using the two techniques correlated very highly (r = 0.999, p < 0.001). 91% of the total new T2 lesion volume was from enlargement of pre-existent lesions and only 9 % from new, discrete, lesions. No relationship was seen between the traditional measure of net gain in T2 lesion load and either measure of atrophy. However, the fully-automated measure of total new T2 load correlated with both measures of atrophy (SIENA technique, r= -0.37, p= 0.02; six slice measure, r = -0.41, p = 0.01). There was no relationship between the MRI measures and changes in the EDSS. CONCLUSION: Both of the new image analysis techniques appear to be promising as sensitive markers for disease progression in PPMS. The correlation of total new T2 lesion volume with the progression of cerebral atrophy (which is known to be a consequence of axonal loss in progressive disease), compared with a lack of correlation with the traditional net gain in T2 lesion load is interesting and suggests that the total new T2 lesion volume may ultimately be the most useful measure.

Adult↗

PubMedDate not supplied

Lobar atrophy of the liver.

Lobar atrophy of the liver due to causes other than liver tumor or liver cirrhosis is a relatively rare pathological condition, and there are only a few reports in the literature. We report six such cases and try to evaluate the relationship between lobar atrophy and portal flow disturbance. The patients could be divided into two groups according to the site of the atrophy: those with atrophy of the left lobe (two cases) and those with atrophy of the right lobe (four cases). The two cases with atrophy of the right lobe had hepatholithiasis in the involved segments, but the cause was not determined in the remaining four cases. In all six cases, portal flow disturbance was noted, including invisibility of the portal vein in four cases, narrowing in one case, and portal thrombus in one case. Collateral circulation was not recognized in any of our cases. Of interest is the mode of lobar atrophy. Atrophy of the right lobe was always associated with marked enlargement of the left lobe, but that of the left lobe did not induce an enlargement of the right lobe.

Aged↗

PubMed1983

The relationship between axon diameter, myelin thickness and conduction velocity during atrophy of mammalian peripheral nerves.

The atrophy of cutaneous (sural) and muscle (medial gastrocnemius) nerves proximal to a ligation were studied in cats for periods up to 9 months, using light and electron microscopy, conduction velocity measurements and computer simulations. As atrophy proceeds, nerve fibres become increasingly non-circular. Cross-sectional areas of axons and fibres (axon + myelin) were measured. The diameters of equivalent circles (having the same axon and fibre cross-sectional area) were then calculated. A linear relation was found between axon diameter and fibre diameter, but the slope decreased as atrophy continued. This indicates that the axon cross-sectional area decreases relatively more than the total fibre area. Reduction in conduction velocity correlates more closely with reduction in axon diameter than fibre (axon + myelin) diameter. The ratio of the inner (axon) perimeter to the outer (myelin) perimeter remains constant at or near the optimal value of 0.6 for conduction in all groups of fibres at all periods of atrophy. Furthermore, the thickness of the myelin remains constant for a given perimeter over the entire period of atrophy studied. This suggests that the number of turns of myelin and the length of each turn remain unchanged during peripheral nerve atrophy. A simple geometric model explains how this can occur without gaps developing between the axon and myelin or between the turns of myelin. The Frankenhaeuser-Huxley equations for conduction in myelinated nerve fibres predict changes in conduction velocity similar to those observed, if the axons atrophy without changes in myelin. The advantages of this mode of atrophy are discussed.

Animals↗

PubMed1993

Chronological atrophy after transient middle cerebral artery occlusion in rats.

We studied the development of brain atrophy after transient focal ischemia in rats. The animals were subjected to cerebral ischemia induced by embolization of the right middle cerebral artery (MCA) for 60 min. The brains were studied morphologically 7 days, 1 month, 3 months and 9 months after recirculation. In addition, the effects of a new calcium antagonist, KB-2796, and a glutamate receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX); were evaluated in this model 1 month after ischemia. The hemispheric volume of the ipsilateral ischemic side, expressed as a percentage of that on the contralateral non-ischemic side, was 99% in the sham operation group, 94% at 7 days, 87% at 1 month, 68% at 3 months and 65% at 9 months. Atrophy of the striatum and cortex, but not the hippocampus, was observed 1 month after ischemia. Atrophy of the ipsilateral substantia nigra and the thalamus, which are remote from the ischemic region, was observed 7 days and 1 month, respectively, after ischemia. Correlations between the extent of the atrophy in the striatum and that in the substantia nigra and between the extent of the atrophy in the cortex and in the thalamus were statistically significant. Treatment with KB-2796 or DNQX administered intraperitoneally at a dose of 10 mg/kg twice 30 min before ischemia and immediately after ischemia was effective in reducing the extent of atrophy in both the ipsilateral ischemic and non-ischemic regions. These results suggest that brain atrophy on the ipsilateral ischemic side develops time-sequentially after transient focal ischemia and that ischemia affects not only the primary ischemic focus but also remote regions through transsynaptic connections, and that KB-2796 and DNQX have beneficial effects on atrophy in the chronic phase after ischemia.

Animals↗

PubMed1990

Mild brain atrophy in early HIV infection: the lack of association with cognitive deficits and HIV-specific intrathecal immune response.

Brain MRI and/or CT were performed on 72 HIV-infected patients at various stages of the disease, and on 34 controls. The neuroradiological findings were related to duration of the infection, neurological symptoms, and cognitive abnormalities as well as to immunological findings in the CSF and blood. All types of brain atrophy were more severe and more frequent in HIV-infected subjects than in controls. Patients with neurological symptoms, those with advanced HIV infection, and patients with a duration of HIV infection of more than 4 years showed the most severe and most frequent neuroradiological abnormalities, including central and cortical atrophy, brain stem atrophy, and cerebellar atrophy. Subjects with cognitive defects exhibited more severe central atrophy than cognitively intact patients. However, slight brain atrophy and/or parenchymal lesions were found in 57% of cognitively intact HIV-seropositive individuals. Patients with brain atrophy and those with radiologically normal brain, both showed increased intrathecal synthesis of total IgG, and intrathecal HIV-antibody synthesis. However, a declined general immune response and a lowered CSF leukocyte count were seen predominantly in patients with brain atrophy. The results suggest that subcortical, neurologically "silent" areas of brain white matter are an early target of HIV infection.

AIDS Dementia Complex↗

PubMed2006

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease.

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.

Adult↗

PubMed2005

Distribution of brain atrophy in behavioral variant frontotemporal dementia.

Marked brain atrophy occurs in frontotemporal dementia (FTD) yet substantial variation between cases is seen. Recently, a four-level staging scheme which reflects increasing disease duration, severity of dementia and degree of neurodegeneration was described. In the present study, the extent and magnitude of atrophy in behavioral variant FTD and its relationship to disease duration and pathological subtype was further evaluated by quantifying the volume of 30 anatomically-defined regions. A validated point count technique was applied to 17 patients with FTD (9 Pick's disease, 6 dementia lacking distinctive histology, 2 FTD with motor neuron disease) and 21 controls. Atrophy was seen in all brain regions except the inferior frontal cortex and area 37. As might be expected, increasing severity of atrophy occurred with increasing disease duration and stage however measurable atrophy was more widespread than indicated by the staging scheme. Furthermore, severity of atrophy was not related to pathological subtype. Frontal, limbic and temporal regions appeared to be severely affected early in the disease process with temporal lobe atrophy the best predictor of disease duration. White matter, more posterior regions and the subcortex were affected later in the disease. These findings demonstrate a pattern of selective vulnerability which progresses over time. Furthermore, they demonstrate that although patients with a similar clinical subtype may have differing underlying histopathology, the pattern, severity and progression of brain atrophy is the same. This suggests that the regional pattern of neurodegeneration, rather than the type of histopathology influences the clinical syndrome in FTD.

Aged↗

PubMed2005

In vivo MRI and histological evaluation of brain atrophy in APP/PS1 transgenic mice.

Regional cerebral atrophy was evaluated in APP/PS1 mice harboring mutated transgenes linked to familial Alzheimer's disease, using complementary methods. In vivo high resolution MRI was selected for measurements of brain atrophy and associated cerebrospinal fluid dilation; histological analysis was performed to reveal localized atrophies and to evaluate amyloid burden. Young APP/PS1 mice examined at a pre-amyloid stage (10 weeks) showed disruption in development (reduced intracranial and brain volumes). Comparison of young and old (24 months) mice, indicated that both APP/PS1 and control brains endure growth during adulthood. Aged APP/PS1 animals showed a moderate although significant global brain atrophy and a dilation of CSF space in posterior brain regions. The locus of this atrophy was identified in the midbrain area and not, as expected, at isocortical/hippocampal levels. Atrophy was also detected in fiber tracts. The severity of brain atrophy in old APP/PS1 mice was not correlated with the extent of cerebral amyloidosis. The relevance of current transgenic mouse models for the study of brain atrophy related to Alzheimer's disease is discussed.

Age Factors↗

PubMed2006

Atrophy rates of the cingulate gyrus and hippocampus in AD and FTLD.

This study explores the diagnostic utility of atrophy rates of the cingulate gyrus, its subdivisions and the hippocampus in Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). Regions were manually outlined on MR images of a group of pathologically or genetically confirmed patients with AD (n=19), FTLD (n=8) and age-matched controls (n=11). Mean (S.D.) atrophy rates (%year(-1)) in the cingulate in controls, AD and FTLD were -0.3 (1.2), 5.9 (3.5), and 8.6 (4.1), respectively. Hippocampal atrophy rates in controls, AD and FTLD were -0.1 (0.8), 3.4 (2.2), and 5.2 (5.4), respectively. Atrophy rates were significantly higher in the cingulate and hippocampi in AD and FTLD compared with controls (p<0.01). There was evidence of a difference in trends of atrophy in the cingulate (more anterior in FTLD and more posterior in AD) between the disease groups (p=0.03). Cingulate atrophy rates discriminated perfectly between FTLD and controls. Significantly better discrimination between AD and controls was obtained by hippocampal rather than cingulate rates. In conclusion, cingulate atrophy is as significant a feature of AD and FTLD as hippocampal atrophy.

Alzheimer Disease↗