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Duodenal mucosal morphometry of elderly patients with small intestinal bacterial overgrowth: response to antibiotic treatment.

Microscopic changes in duodenal biopsy specimens from 16 elderly patients with small-bowel bacterial overgrowth were studied before and after cyclical courses of antibiotic treatment, using computer-aided morphometry measurements as well as visual assessment. Twenty-three subjects in the same age group with no evidence of intestinal disorder were studied as controls. Mean villus height was significantly reduced in the pre-treatment study compared to the post-treatment measurements and those in controls. Similar significant differences were found in mean crypt depth and total mucosal thickness. The mean intra-epithelial lymphocyte count was raised before treatment and fell after treatment to a level similar to that of the controls. The mean lymphocyte count in the peripheral blood rose significantly after treatment. This study provides objective evidence of microscopic structural changes in the bacterial overgrowth syndrome in old age. The return to normality after antibiotic treatment suggests that these changes are directly attributable to the presence of bacteria in the gut lumen.

Aged↗

Lymphoid-rich effusions. Diagnosis by morphometry using the CAS 200 System.

Lymphoid-rich effusions frequently present diagnostic problems in clinical cytology. In the authors' previous studies, most lymphoid-rich effusions had been correctly classified as benign lymphocytosis or malignant lymphoma by an experimental computerized interactive morphometry system, in which randomly selected lymphoid nuclear profile images were measured in Papanicolaou fixed and stained cytospin smears. The present study used the CAS 200 System and criteria from the previously described rule-based expert system to classify similar preparations of 134 lymphoid rich pleural, peritoneal, and pericardial effusions (90 benign lymphocytoses, 36 malignant lymphomas, and 8 chronic lymphocytic leukemias). A total of 98.9% of the benign lymphocytoses and 88.9% of the malignant lymphomas were correctly classified (predictive values of correct diagnoses 95.7% and 97.3%, respectively). Chronic lymphocytic leukemias could not be distinguished from benign lymphocytoses by nuclear profile areas. Optical density histograms of benign, lymphomatous, and chronic lymphocytic leukemias effusions are described. Advantages and limitations of image analysis and immunocytochemistry are discussed.

Ascitic Fluid↗

Computerized interactive morphometry. An expert system for the diagnosis of lymphoid-rich effusions.

The authors present experimental techniques for the diagnosis of malignant lymphoma and benign lymphocytosis in lymphoid-rich effusions with the use of an inexpensive microcomputer-based video system for computerized interactive morphometry (CIM). Lymphoid cells were randomly selected by a trained observer from real-time images of Papanicolaou-fixed and -stained cytospin smears prepared from pleural, peritoneal, or pericardial effusions. The lymphoid cells were classified by the instrument, based on the size and shape of their nuclear profiles. The morphometric data collected by the instrument were interpreted by a simple rule-based expert system that classified the smears as benign or malignant. One hundred four cases, including 28 malignant lymphomas, 63 benign lymphocytoses, 8 chronic lymphocytic leukemias, and 5 cases with incomplete immunopathologic data, were studied retrospectively. Sixty-three of these effusions had been stained to detect light chain monoclonality. Ninety-one effusions were correctly classified by the expert system. There were four potential false negative diagnoses and one potential false positive diagnosis by the CIM system. Eight effusions from patients with chronic lymphocytic leukemia (CLL) were consistently classified as benign. Although the author's series of patients with a history of CLL is small, their results suggest that CIM is unsuitable for the diagnosis of malignancy in these effusions. If only those effusions from patients with a history of CLL are excluded, the predictive value of a diagnosis of malignant lymphoma was 96.5%, whereas the predictive value of a diagnosis of benign lymphocytosis was 94.0%.

Algorithms↗

Computerized interactive morphometry and the diagnosis of lymphoid-rich effusions.

An experimental computerized interactive morphometry system for the classification of lymphoid-rich effusions is presented. The relatively inexpensive microcomputer-based system was assembled in our laboratory with commercially available hardware and software. One hundred twenty-two effusions (86 benign lymphocytoses, 26 lymphomas, and 10 chronic lymphocytic leukemias) were studied. Lymphoid cells were selected randomly by the system from real-time images of Papanicolaou-fixed and stained cytospin smears of pleural, peritoneal, and pericardial effusions. Parameters of nuclear shape, area, and optical density were measured automatically. Multiparameter statistical procedures of discriminant classificatory analysis analyzed the distribution of lymphoid nuclear profile integrated optical density to yield three groups of effusions, each with a predictive value of diagnosis of 100%. Neither these statistical procedures nor a simple rule-based expert system accurately classified chronic lymphocytic leukemia effusions based on the distribution of lymphoid nuclear profile area. When chronic lymphocytic leukemia effusions were excluded, however, the predictive values of a diagnosis of lymphoma by statistical analysis and by rule-based expert system were 92.3% and 88.9%, respectively, whereas the predictive values of a diagnosis of benign lymphocytosis were 97.7% and 91.3%, respectively. Potential applications and limitations of this technology for the diagnosis of lymphoid-rich effusions are discussed.

Cell Nucleus↗

Image analyser-assisted morphometry of the locus coeruleus in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis.

Several observations suggest that neuronal shrinkage rather than cell death is the major phenomenon in neurodegenerative diseases. In order to make this distinction, smaller cells should also be included in cell counts. Also, morphometric determination of total cell numbers of brain structures is required. Morphometry was performed on the locus coeruleus using a newly developed method to delineate this nucleus from five patients who had died with Alzheimer's disease, five with Parkinson's disease, five with amyotrophic lateral sclerosis and from five control subjects who had died from causes that would not have affected the locus coeruleus. The length and volume of the locus coeruleus and its total number of large pigmented neurons, small unpigmented neurons and glial cells were determined. Since reliable delineation of the boundaries of the locus coeruleus is a requirement for the determination of total cell numbers, an image analyser-assisted procedure was developed. In Alzheimer's disease we found an 82% decrease in the number of large pigmented neurons and a 39% decrease of small unpigmented neurons. In Parkinson's disease, we found a 39% decrease of large pigmented neurons but also a 44% (though not significant) increase of small unpigmented neurons, which is indicative of a shift from large pigmented neurons to small unpigmented neurons in Parkinson's disease. The large pigmented/small unpigmented neuron number ratio was greatly and significantly reduced in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. These findings support the hypothesis that the decrease of large pigmented neurons of the locus coeruleus in some neurodegenerative diseases is not entirely due to cell death, but rather to cell shrinkage and a loss of phenotype. This hypothesis may have consequences for the development of therapeutic strategies since atrophied cells can be activated. On the other hand our data confirm that, at least in Alzheimer's disease, large pigmented neurons do also undergo cell death.

Aged↗

Age-related cortical grey matter reductions in non-demented Down's syndrome adults determined by MRI with voxel-based morphometry.

Ageing in Down's syndrome is accompanied by amyloid and neurofibrillary pathology the distribution of which replicates pathological features of Alzheimer's disease. With advancing age, an increasing proportion of Down's syndrome subjects >40 years old develop progressive cognitive impairment, resembling the cognitive profile of Alzheimer's disease. Based on these findings, Down's syndrome has been proposed as a model to study the predementia stages of Alzheimer's disease. Using an interactive anatomical segmentation technique and volume-of-interest measurements of MRI, we showed recently that non-demented Down's syndrome adults had significantly reduced hippocampus, entorhinal cortex and corpus callosum sizes with increasing age. In this study, we applied the automated and objective technique of voxel-based morphometry, implemented in SPM99, to the analysis of structural MRI from 27 non-demented Down's syndrome adults (mean age 41.1 years, 15 female). Regional grey matter volume was decreased with advancing age in bilateral parietal cortex (mainly the precuneus and inferior parietal lobule), bilateral frontal cortex with left side predominance (mainly middle frontal gyrus), left occipital cortex (mainly lingual cortex), right precentral and left postcentral gyrus, left transverse temporal gyrus, and right parahippocampal gyrus. The reductions were unrelated to gender, intracranial volume or general cognitive function. Grey matter volume was relatively preserved in subcortical nuclei, periventricular regions, the basal surface of the brain (bilateral orbitofrontal and anterior temporal) and the anterior cingulate gyrus. Our findings suggest grey matter reductions in allocortex and association neocortex in the predementia stage of Down's syndrome. The most likely substrate of these changes is alterations or loss of allocortical and neocortical neurons due to Alzheimer's disease-type pathology.

Adult↗

A study of bipolar disorder using magnetization transfer imaging and voxel-based morphometry.

Bipolar disorder (BP) traditionally has been considered as a recurrent illness with full recovery between episodes, and the absence of neuropathological abnormalities has usually been taken for granted. In recent times, the realization that, for many BP carries a poor prognosis, that cognitive deficits are often persistent and that structural brain abnormalities are detectable with modern imaging techniques has spurred the search for its neuropathological substrate. The shortcomings of post-mortem studies make the use of imaging techniques sensitive to neuropathological changes compelling. We report here the first study of BP patients using two such techniques in conjunction: magnetization transfer imaging (MTI) and voxel-based morphometry (VBM). Thirty-nine patients with BP (13 males and 26 females; 28 with BPI and 11 with BPII) and 35 healthy controls were investigated. Both high-resolution volumetric T1-weighted images and MT images were acquired from all subjects. Images were processed using a voxel-by-voxel analysis in statistical parametric mapping 2 (SPM2). The magnetization transfer ratio MTR, an index indicative of loss of macromolecular density, was reduced in the right subgenual anterior cingulate and adjacent white matter in bipolar patients compared with controls. VBM did not reveal significant volumetric differences between BP patients and controls in grey and white matter, but white matter density was significantly reduced bilaterally in prefrontal areas encompassing fronto-striatal connections. Our findings suggest that subtle abnormalities are present in the anterior cingulate and subgyral white matter in patients with BP in the absence of significant volumetric changes. These findings are in keeping with those of previously reported neuropathological studies and illustrate important similarities (involvement of the anterior cingulate) and differences (lack of widespread cortical abnormalities in BP) with our previous studies in schizophrenic patients using the same methodology.

Adult↗

Brain morphometry and IQ measurements in preterm children.

Although IQ is thought to remain relatively stable in the normal population, a decline in IQ has been noted in children born preterm. It is not clear, however, to what extent the inclusion of children with clear neurological damage has influenced these findings. We examined IQ scores obtained in childhood and then again in adolescence from a group of children born at 30 weeks gestation or less who had been classified as neurologically normal at 7.5-8 years. They showed a significant decline in mean IQ scores over time. MRI scans obtained from a subset of children at adolescence were read as normal in approximately 50% of cases and, in the others, there were no consistent relationships between radiological abnormalities and IQ results. Such children can, however, have relatively subtle brain abnormalities that are not seen on conventional MRI, and we hypothesized that these would be related to declines in IQ. Voxel-based morphometry (VBM) analyses of the MRI scans revealed that absolute IQ scores were related to areas in both the parietal and temporal lobes. The analyses also showed that frontal and temporal lobe regions were associated with the decline in VIQ, while occipital and temporal lobe regions (including the hippocampi) were associated with the decline in PIQ. Hippocampal volume measurements were consistent with the VBM findings. We concluded that preterm children are at risk of declining IQ over time even if they have not suffered obvious neurological damage and that the decline is associated with specific neural regions. Whether this is true of children born at >30 weeks gestation and what other factors predispose to this decline have yet to be determined.

Adolescent↗

Morphometry of the amusic brain: a two-site study.

Congenital amusia (or tone deafness) is a lifelong disability that prevents otherwise normal-functioning individuals from developing basic musical skills. Behavioural evidence indicates that congenital amusia is due to a severe deficit in pitch processing, but very little is known about the neural correlates of this condition. The objective of the present study was to investigate the structural neural correlates of congenital amusia. To this aim, voxel-based morphometry was used to detect brain anatomical differences in amusic individuals relative to musically intact controls, by analysing T1-weighted magnetic resonance images from two independent samples of subjects. The results were consistent across samples in highlighting a reduction in white matter concentration in the right inferior frontal gyrus of amusic individuals. This anatomical anomaly was correlated with performance on pitch-based musical tasks. The results are consistent with neuroimaging findings implicating right inferior frontal regions in musical pitch encoding and melodic pitch memory. We conceive the present results as a consequence of an impoverished communication in a right-hemisphere-based network involving the inferior frontal cortex and the right auditory cortex. Moreover, the data point to the integrity of white matter tracts in right frontal brain areas as being key in acquiring normal musical competence.

Auditory Perceptual Disorders↗

Gender differences in the normal lateralization of the supratemporal cortex: MRI surface-rendering morphometry of Heschl's gyrus and the planum temporale.

Gender differences in hemispheric asymmetry for language functioning have been reported in the neuropsychological literature. Despite numerous reports of anatomic asymmetries in corresponding cortical regions, the possibility of gender dimorphism in the putative neuroanatomical substrate of language has not been systematically examined in vivo. We assessed asymmetry of the planum temporale (PT), a supratemporal region of auditory association cortex, in 12 normal, right-handed females and 12 age-matched right-handed males with the aid of MRI surface-rendering morphometry. Bilateral areas were also assessed for Heschl's gyrus (HG), a supratemporal region of primary auditory cortex where no asymmetry was anticipated. We found a significant interaction between gender and hemisphere for the PT, with males having significantly larger left versus right PTs. Left-right differences in PT area were not significant among females (10 of 12 males showed leftward lateralization of the PT, vs 5 of 12 females). No main effect of gender was found for total (left + right) PT area, and no asymmetries or gender effects were detected for HG. This finding of gender dimorphism in PT area is consistent with evidence for reduced asymmetry among females in the lateralization of language functions attributable to the supratemporal cortex. The implications for theories about interactions between sex hormones and the development of brain asymmetries are discussed.

Adult↗

Fiber connections between the cerebral cortex and the corpus callosum in Alzheimer's disease: a diffusion tensor imaging and voxel-based morphometry study.

Regional cortical atrophy in Alzheimer's disease (AD) most likely reflects the loss of cortical neurons. Several diffusion tensor imaging studies reported reduced fractional anisotropy (FA) in the corpus callosum in AD. The aim of this study was to investigate the association between reduced FA in the corpus callosum and gray matter atrophy in AD. Thirteen patients with AD with a mean (+/-standard deviation) age of 68.3 years (+/-11.5) and mean Mini Mental State Examination (MMSE) score of 21.8 (+/-4.8) were recruited. There were 13 control subjects with a mean age of 66.7 years (+/-6.4) and MMSE of 29.1 (+/-0.7). We used voxel-based morphometry of gray matter maps and region of interest-based analysis of FA in the corpus callosum. FA values of the anterior corpus callosum in AD patients were significantly correlated with gray matter volume in the prefrontal cortex and left parietal lobes. FA values of the posterior corpus callosum were significantly correlated with gray matter volume in the bilateral frontal, temporal, right parietal, and occipital lobes. In control subjects, no correlations were detected. Our findings suggest that decline of FA in the corpus callosum may be related to neuronal degeneration in corresponding cortical areas.

Aged↗

Automated semen analysis: 'zona pellucida preferred' sperm morphometry and straight-line velocity are related to pregnancy rate in subfertile couples.

BACKGROUND: Standard semen analysis has low objectivity and reproducibility and is not closely related to fertility. We assess the prognostic value of automated measurements of sperm motility and morphology. METHODS: During 1997-1999, 1191 infertile couples with no known absolute barrier to conception were assessed by conventional semen analysis, and automated measurements of average straight-line velocity (VSL) and the percentage of sperm with characteristics that conform to those of sperm which bind to the zona pellucida of the human oocyte (%Z). During follow-up to 2001, there were 336 natural pregnancies. RESULTS: Only %Z, VSL and female age were independently significantly related to pregnancy rate by Cox regression analysis. Pregnancy rate was higher with above average %Z and VSL, indicating a continuous rather than a threshold relationship. The likelihood of pregnancy within 12 cycles can be evaluated for specific values of %Z, VSL and female age using the Cox regression model. CONCLUSIONS: The automated semen measures of sperm morphometry (%Z) and velocity (VSL) are related to pregnancy rates in subfertile couples and should assist clinicians in counselling subfertile patients about their prognosis for a natural pregnancy. Objective automated methods should replace the traditional manual assessments of semen quality.

Adult↗

Renal function and morphometry in the dwarf rat following a reduction in renal mass.

BACKGROUND: The compensatory increase in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) which follows a reduction in renal mass may be mediated by growth hormone, a renal vasodilator. METHODS: GFR, ERPF and glomerular morphometry were assessed in the dwarf rat, selectively deficient in GH, and compared its Lewis base strain. Studies were performed 21-days after sham-operation, unilateral nephrectomy or subtotal nephrectomy in age-matched animals. GFR and ERPF were assessed from the renal clearance of inulin and p-aminohippurate measured under barbiturate anaesthesia. RESULTS: The dwarf rat had a lower GFR and ERPF than the Lewis rat, in proportion to its lower body weight and lower kidney weight. Kidneys from the dwarf rat had a similar number of glomeruli to the Lewis, but smaller glomerular components in proportion to a lower kidney weight. Following unilateral nephrectomy, GFR (dwarf + 58%, Lewis + 53%) and ERPF (dwarf + 58%, Lewis + 52%) increased to a similar degree in both rat strains. Glomerular diameter, volume and capillary surface area increased in proportion to kidney growth, although compensatory renal growth (dwarf + 62%, Lewis + 78%) was somewhat lower in the dwarf. Following 5/6 subtotal nephrectomy, GFR (dwarf + 143%, Lewis + 171%) increased to a similar degree in both rat strains while ERPF (dwarf + 108%, Lewis + 48%) and compensatory renal growth (dwarf + 115%, Lewis + 86%) were greater in the dwarf than the Lewis rat. Subtotal nephrectomy was also associated with an increase in the thickness of the glomerular basement membrane in both rat strains. CONCLUSIONS: The results do not support a role for GH in the compensatory increase in renal function or hypertrophy which follows a reduction in renal mass, excluding this as a potential mechanism for GH-dependent renal scarring.

Animals↗

Voxel-based morphometry of brain SPECT can detect the presence of active central nervous system involvement in systemic lupus erythematosus.

OBJECTIVE: To determine the value of voxel-based morphometry (VBM) of brain SPECT (single-photon emission computed tomography) images (BSI) in discriminating active central nervous system (CNS) manifestations in systemic lupus erythematosus (SLE) patients. PATIENTS AND METHODS: Forty SLE patients (mean age 33 yrs) and 33 normal volunteers were submitted to BSI. SLE patients were screened for the presence of CNS involvement following the American College of Rheumatology (ACR) case definition. Patients with CNS infections, uraemia, diabetes and previous ischaemic or haemorrhagic stroke were excluded. Magnetic resonance imaging (MRI) scans were obtained in a 2T scanner (Elscint Prestige) with T1- and T2-weighted images. BSI were performed after injection of 1110 MBq (30 mCi) of (99m)Tc-ECD (ethyl-cysteinate-dimer). BSI were analysed using the statistical parametric mapping. After normalization, segmentation and smoothing the groups of SLE patients with active and inactive CNS manifestations and healthy volunteers were compared using VBM. Post-processed images were compared voxel-by-voxel using t-test in order to determine differences of intensity between groups. This analysis included grand mean scaling, proportional threshold masking (set to 0.4) and implicit masking. A P-value of 0.001 and cluster size of 32 were taken into consideration. RESULTS: VBM analyses of BSI did not show any differences between SLE patients with inactive CNS involvement and normal controls. However, the group of SLE patients with active CNS involvement had a global hypoperfusion, more intense in the frontal, dorsolateral and medial temporal lobe when compared with SLE patients without CNS involvement (P = 0.001) and healthy volunteers (P = 0.001). CONCLUSION: VBM of BSI is a useful and objective method for detecting perfusion abnormalities in SLE patients, which is indicative of active CNS involvement. However, it is not helpful in differentiating the clinical sub-types of CNS involvement according to the ACR classification.

Adolescent↗

Morphometry of single small enhancing computed tomographic lesions: outcome and effect of albendazole therapy.

Single small enhancing computerized tomographic (CT) lesions (SSECTLs) are common in children with focal seizures. However, there is a paucity of systematic information regarding their morphometry, effect of albendazole therapy and long-term outcome. The objectives were to study the pattern of SSECTL on radiological follow up, alterations made by albendazole therapy, and correlation with seizure recurrence. A randomized, placebo controlled, double blind trial was carried out at the Advanced Pediatric Center, PGIMER, an urban tertiary-care teaching hospital. Sixty-three children between 2 and 12 years of age with focal seizures for < 3 months and SSECTLs were included in the study. All children were randomly assigned to receive either albendazole (15 mg/kg/day) or placebo for 28 days. CT scan was done at 1 and 3 months after beginning treatment. Codes opened after 6 months of recruitment in the study showed that 31 had received albendazole and 32 had received placebo. Over a period of 3 months, natural resolution of SSECTL passed through many stages. Albendazole was seen to accelerate this natural process as evident by the progression of various morphometric markers. An increase in the size of the lesion was associated with early seizure recurrence.

Administration, Oral↗

Angiogenesis and morphometry of bovine placentas in late gestation from embryos produced in vivo or in vitro.

The objective of this study was to determine the effects of in vitro embryo production on angiogenesis and morphometry of the bovine placenta during late gestation. Blastocysts produced in vivo were recovered from superovulated Holstein cows. Blastocysts produced in vitro were obtained after culture of in vitro-matured and -fertilized Holstein oocytes. Single blastocysts from each production system were transferred into heifers. Fetuses and placentas were recovered on Day 222 of gestation (in vivo, n=12; in vitro, n=12). Cotyledonary and caruncular tissues were obtained for quantification of vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor-gamma (PPARgamma) mRNA and protein. Tissue sections of placentomes were prepared for morphometric analysis. Fetuses and placentas were heavier from embryos produced in vitro than from embryos produced in vivo. More placentas from embryos produced in vitro had an excessive volume of placental fluid. There was no effect of treatment on the expression of mRNA for VEGF and PPARgamma in either cotyledonary or caruncular tissues. The expression of VEGF protein in cotyledons and caruncles as well as the expression of PPARgamma protein in cotyledons were not different between the in vitro and in vivo groups. However, caruncles from the in vitro group had increased expression of PPARgamma protein. The total surface area of endometrium was greater for the in vitro group compared with controls. In contrast, the percentage placentome surface area was decreased in the in vitro group. Fetal villi and binucleate cell volume densities were decreased in placentomes from embryos produced in vitro. The proportional tissue volume of blood vessels in the maternal caruncles was increased in the in vitro group. Furthermore, the ratios of blood vessel volume density-to-placentome surface area were increased in the in vitro group. In conclusion, these findings are consistent with the concept that compensatory mechanisms exist in the vascular beds of placentas from bovine embryos produced in vitro.

Animals↗

Effects of embryo culture on angiogenesis and morphometry of bovine placentas during early gestation.

The objective of this study was to determine the effects of undefined and semidefined culture systems for in vitro embryo production on angiogenesis and morphometry of bovine placentas during early gestation. Blastocysts produced in vivo were recovered from superovulated Holstein cows and served as controls. Blastocysts produced in vitro were exposed to either serum-supplemented medium with cumulus cell coculture (in vitro-produced with serum; IVPS) or modified synthetic oviductal fluid medium without serum or coculture (mSOF). Single blastocysts from each production system were transferred into heifers. Fetuses and placentas were recovered on Day 70 of gestation. Cotyledonary tissues were obtained for quantification of vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor-gamma (PPARG) mRNA and protein. Samples of placentomes were prepared for immunocytochemistry and histological analysis. Placentas from the mSOF group were heavier and had the fewest placentomes, least placental fluid, and lowest placental efficiency (fetal weight/placental weight) compared with the in vivo and IVPS groups. There was no effect of embryo culture system on volume densities of fetal villi or maternal endometrium within placentomes. The volume density of fetal pyknotic cells was increased in placentomes in the mSOF group compared with the in vivo and IVPS groups. Placentomes in the mSOF group had decreased densities of blood vessels and decreased levels of VEGF mRNA in cotyledonary tissue. In conclusion, compared with placentas from embryos produced in vivo or in vitro using an undefined culture system, placentas from embryos produced in vitro using a semidefined culture system exhibited a greater degree of aberrant development of the placenta during early gestation.

Animals↗

Mapping gray matter loss with voxel-based morphometry in mild cognitive impairment.

We used voxel-based morphometry to comprehensively and objectively map gray matter loss in 22 patients with amnestic mild cognitive impairment, defined as progressive isolated episodic memory decline. Compared with 22 age-matched healthy controls, patients had highly significant gray matter loss predominantly affecting the hippocampal region and cingulate gyri (posterior and subcallosal part of the anterior), and extending into the temporal neocortex. Compared with 16 age-matched patients with mild Alzheimer's disease, gray matter density was significantly preserved in mild cognitive impairment in the posterior association cortex. This pattern of gray matter loss in mild cognitive impairment agrees with but considerably expands upon previous region-of-interest based MRI studies, and is highly consistent with the course of neurofibrillary tangles across aging and Alzheimer's disease.

Aged↗