Hippocampal and amygdalar local structural differences in elderly patients with schizophrenia.

OBJECTIVES: Morphological abnormalities have been reported for the hippocampi and amygdalae in young schizophrenia patients, but very little is known about the pattern of abnormalities in elderly schizophrenia patients. Here we investigated local structural differences in the hippocampi and amygdalae of elderly schizophrenia patients compared with healthy elderly subjects. We also related these differences to clinical symptom severity. DESIGN: 20 schizophrenia patients (mean age: 67.4 ± 6.2 years; Mini-Mental State Exam: 22.8 ± 4.4) and 20 healthy elderly subjects (70.3 ± 7.5 years; 29.0 ± 1.1) underwent high resolution magnetic resonance imaging of the brain. The Radial Atrophy Mapping technique was used to reconstruct the 3D shape of the amygdala and the hippocampus. Local differences in tissue reductions were computed between groups and permutation tests were run to correct for multiple comparisons, in statistical maps thresholded at p = 0.05. RESULTS: Significant tissue reduction was observed bilaterally in the amygdala and hippocampus of schizophrenia patients. The basolateral-ventral-medial amygdalar nucleus showed the greatest involvement, with over 30% local tissue reduction. The centro-medial, cortical, and lateral nuclei were also atrophic in patients. The hippocampus showed significant tissue loss in the medio-caudal and antero-lateral aspects of CA1, and in medial section of its left head (pre- and para-subiculum). In the left amygdala and hippocampus, local tissue volumes were significantly correlated with negative symptoms. CONCLUSIONS: Tissue loss and altered morphology were found in elderly schizophrenia patients. Tissue loss mapped to amygdalo-hippocampal subregions known to have bidirectional and specific connections with frontal cortical and limbic structures and was related to clinical severity.

Potential Neuroprotective Effect of Melatonin in the Hippocampus of Male BTBR Mice.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder identified by impairments in common social interactions and repetitive behaviors. In ASD patients, substantial morphological alterations have been observed in the hippocampus, which represents an important region for the development of social skills. Melatonin, commonly found in many foods and plants, is also produced by the pineal gland. This indolamine, known to regulate the circadian rhythm, shows antioxidant and anti-inflammatory properties. We therefore hypothesized that melatonin may reduce oxidative stress and inflammation in the hippocampus of ASD patients. We explored our hypothesis using the BTBR mouse, a well-regarded murine transgenic model for ASD. Immediately after weaning, male BTBR and C57BL/6 mice underwent an 8-week treatment with melatonin or vehicle. Later, through immunohistochemistry and the immunoblotting analysis of the hippocampus, we evaluated the overall expression and cellular localization of Nrf2 and SOD1, two enzymes involved in the oxidative stress response. Similarly, we evaluated NLRP3 and NFkB, two mediators of inflammation, and GAD67, an enzyme responsible for the synthesis of GABA. Ultimately, we addressed melatonin's potential to regulate iron metabolism through a DAB-enhanced Perls reaction assay. Results showed melatonin's potential for modulating the analyzed markers in BTBR mice, suggesting a potential neuroprotective effect in ASD patients.

Quality of Life and Its Psychosocial Predictors among Patients with Disorders of Gut-Brain Interaction: A Comparison with Age- and Sex-Matched Controls.

The disorders of gut-brain interaction (DGBIs) are a heterogeneous group of chronic conditions that greatly reduce patients' quality of life (QoL). To date, biopsychosocial factors (such as gastrointestinal symptoms, alexithymia, and interpersonal problems) are believed to contribute to the development and maintenance of DGBIs, but their role in affecting patients' QoL is still under investigation. Out of 141 patients seeking treatment for their gastrointestinal symptoms, 71 were diagnosed with a DGBI (47 females, 66.2%; Mage: 41.49 ± 17.23 years) and were age- and sex-matched to 71 healthy controls (47 females, 66.2%; Mage: 40.45 ± 16.38 years) without any current gastrointestinal symptom or diagnosis. Participants completed a sociodemographic and clinical questionnaire and a survey investigating several psychosocial risk factors. We found greater symptom severity and difficulties in identifying feelings among patients compared to controls. Further, multiple linear regression analyses evidenced that, among patients, higher expressive suppression of emotions, difficulties in identifying feelings and interpersonal problems, and a lower cognitive reappraisal of emotions predicted lower QoL. Data suggest that the QoL of patients with DGBIs is affected not only by common risk factors (e.g., interpersonal problems) but also by specific difficulties in processing and regulating emotions. The implications of these findings are discussed.

The in vivo topography of cortical changes in healthy aging and prodromal Alzheimer's disease.

BACKGROUND: Gray matter atrophy is regarded as a valid marker of neurodegeneration in Alzheimer's disease (AD), but few studies have investigated in detail the topographic changes associated with normal aging. In addition, few studies have compared the changes in the earliest clinical stage of AD (prodromal AD (pAD)) with those of healthy aging. Here we aimed to investigate the topographical distribution of age-related cortical atrophy and to compare it with that associated with prodromal and estabilished AD. METHODS: Structural T1-weighted high-resolution brain magnetic resonance imaging scans were acquired from 60 healthy volunteers (20 young adults, YA: age 32.7 +/- 4.5 years; 40 elderly subjects, HE: age 71.3 +/- 6.2 years), 16 mild cognitive impairment subjects who converted to AD within 2 years (prodromal AD, pAD: age 72.8 +/- 5.4), and 20 mild to moderate AD patients (mAD, age 72.5 +/- 10.3). Cortical gray matter differences were investigated using a surface-based anatomical mesh modeling technique (cortical pattern matching) and region-of-interest (ROI) analyses based on hypothesized brain networks taught to have a functional and a structural link to each other. Differences in cortical atrophy were assessed between groups, as well as the effect of age within groups. RESULTS: HE compared to YA showed a 10-30% deficit in cortical gray matter in widespread frontal, temporal, and parietal regions (p = 0.0001 by permutation testing), 6-13% loss in the visual and sensorimotor cortices (p < 0.01) and up to 13% loss in the direct hippocampal pathway ROIs (p < 0.001). pAD patients showed on average 8-9% cortical loss compared to HE (p < 0.0001), mainly in the left (up to 6% loss, p = 0.06) and right polysynaptic hippocampal pathway ROIs (up to 8% loss, p = 0.01), and in the left and right olfactory/orbitofrontal cortex (up to 12-15% loss, p < 0.001). The pattern of cortical atrophy in mAD versus HE was similar to that in pAD, but was more severe in the direct hippocampal pathway ROIs and sensorimotor, visual and temporal cortices (13-15% loss compared with HE, p < 0.0001). CONCLUSION: Gray matter loss occurs during aging with rates of atrophy even more severe than that observed during the course of AD. These changes may be caused by normal mechanisms. In pAD, cortical atrophy due to disease is milder than that due to aging, maybe resulting from a slowed down velocity of cell loss, but affects specific brain areas. These findings are consistent with the view that AD is not merely accelerated aging.

New Approach to Chronic Back Pain Treatment: A Case Control Study.

BACKGROUND AND OBJECTIVE: Our study compares the clinical outcome of chronic low back pain present for over six months treated with alpha-lipoic acid (ALA) + palmitoylethanolamide (PEA) and myrrh and periradicular infiltrations of oxygen-ozone under CT guide to periradicular steroidal infiltrations in a short (one week), medium (three months) and long-term period (six months). METHODS: We enrolled 246 patients (Group A) with low back pain treated with periradicular infiltrations of oxygen-ozone under CT guide combined with 800 mg/day of ALA + 600 mg/day of PEA + 200 mg/day of myrrh orally. Group B consisted of 176 patients with low back pain treated with periradicular infiltrations of steroids. Patients were clinically monitored one week after the end of treatment, at three months, and at six months using a modified version of McNab's method. RESULTS: In Group A, the one-week clinical follow-up registered a complete remission of painful symptoms in 206 patients (83.7%), and this manifestation remained optimal in 191 patients at the three-month follow-up (77.6%) and in 178 at six months (72.3%). While the results were satisfactory in 28 patients (10.9%) at one week, 32 (13%) in the medium term, and 41 (16.6%) in the long term, non-significant results were found in 12 patients in the control at one week (4.6%), in 23 at three months (9.3%) and in 27 at six months (10.9%). In Group B, at the short-term follow-up we obtained an excellent clinical result in 103 patients (80.5%), while at three months 85 patients reported the persistence of clinical benefit (66.4%) and at six months, 72 (56.2%) reported the same result. The result was rated satisfactory in 11 (8.5%) and poor in 4 (3%). At the three-month follow-up, 23 (18%) reported a satisfactory result, and 20 (15.6%) had a poor result. At six months, 24 (18.8%) reported the persistence of a satisfactory result while for 32 the result was poor (25%). CONCLUSION: The results highlight how the treatment associated with ozone therapy and oral administration of alpha-lipoic acid + palmitoylethanolamide and myrrh can be considered a valid alternative to common therapeutic approaches in the treatment of chronic low back pain.

Oxygen-Ozone Therapy Associated with Alpha Lipoic Acid Plus Palmitoylethanolamide and Myrrh versus Ozone Therapy in the Combined Treatment of Sciatic Pain Due to Herniated Discs: Observational Study on 318 Patients.

BACKGROUND: The aim of our observational study is to compare the therapeutic efficacy of combined treatment of oxygen-ozone therapy and oral treatment with alpha-lipoic acid (ALA) + palmitoylethanolamide (PEA) and myrrh in patients with peripheral neuropathic pain (sciatica) on radicular disc conflict from disc herniation and the results obtained with oxygen-ozone treatment alone. METHODS: We enrolled 318 patients with the neuroradiological diagnosis of disc herniation performed with computed tomography (CT) or magnetic resonance imaging (MRI) and symptoms characterized by low back pain complicated by sciatica, which we divided into two groups. Group A was composed of 165 patients who were treated only with oxygen-ozone therapy with CT-guided intraforaminal technique, while the remaining 153 (Group B) have undergone combined oral treatment with ALA + PEA and myrrh. Follow-up visits for the evaluation of the clinical outcome of the treatment were conducted after 60 ± 8 days using a modified version of McNab's method. RESULTS: At the clinical check-up, 126/165 patients included in Group A had a complete remission of pain (76.4%), while in Group B, 119/153 (77.8%) had a complete remission of pain. CONCLUSION: The results highlight how the treatment associated with ozone therapy and oral administration of alpha-lipoic acid + palmitoylethanolamide and myrrh is preferred over the simple treatment with only ozone in such patients in the phase of greatest acuity of the disease, where the pain appears to be better controlled.

The effect of mission duration on LISA science objectives.

The science objectives of the LISA mission have been defined under the implicit assumption of a 4-years continuous data stream. Based on the performance of LISA Pathfinder, it is now expected that LISA will have a duty cycle of ≈ 0.75 , which would reduce the effective span of usable data to 3 years. This paper reports the results of a study by the LISA Science Group, which was charged with assessing the additional science return of increasing the mission lifetime. We explore various observational scenarios to assess the impact of mission duration on the main science objectives of the mission. We find that the science investigations most affected by mission duration concern the search for seed black holes at cosmic dawn, as well as the study of stellar-origin black holes and of their formation channels via multi-band and multi-messenger observations. We conclude that an extension to 6 years of mission operations is recommended.

APOE4 is associated with greater atrophy of the hippocampal formation in Alzheimer's disease.

Prior studies reported that the hippocampal volume is smaller in Alzheimer's disease patients carrying the Apolipoprotein E ε4 allele (APOE4) versus patients who are non-carriers of this allele. This effect however has not been detected consistently, possibly because of the regionally-specific involvement of the hippocampal formation in Alzheimer's disease. The aim of this study was to analyze the local effect of APOE4 on hippocampal atrophy in Alzheimer's disease patients. Using high-resolution T1-weighted images we investigated 14 patients heterozygous for the ε4 allele (age 72±8 SD years; MMSE 20±4 SD) and 14 patients not carrying the ε4 allele (age 71±10; MMSE 20±5 SD), and 28 age-, sex-, and education-matched controls (age 71±8; MMSE 29±1 SD). The hippocampal formation was outlined with manual tracing and 3D parametric surface models were created for each subject. Radial atrophy was assessed on the whole hippocampal surface using the UCLA mapping technique. E4 carriers and non-carriers did not differ in their level of impairment in global cognition (p=0.91, Mann-Whitney test) or memory (p>0.29). Hippocampal surface analysis showed the typical pattern of CA1 and subicular tissue atrophy in both ε4-carriers and non-carriers compared with controls (e4 carriers: p<0.0002; ε4 non-carriers: p<0.01, permutation test). The left hippocampal volume was significantly smaller in ε4-carriers than non-carriers (p=0.044, Mann-Whitney test), the effect of APOE4 mapping to the subicular/CA1 region (p=0.041, permutation test). Differences were not statistically significant in the right hippocampus (p>0.20, permutation test). These findings show that hippocampal atrophy is greater in APOE4 carriers in regions typically affected by pathology. APOE4 may affect the structural expression of Alzheimer's disease.

Alzheimer's CSF markers in older schizophrenia patients.

OBJECTIVES: Cognitive impairment is prevalent in older schizophrenia patients but its biological basis is unknown. Neuropathological studies have not revealed Alzheimer disease (AD) lesion burden but in vivo data are lacking. METHOD: We investigated the concentrations of CSF biomarkers of brain amyloidosis (Abeta42) and neurodegeneration (total and p-tau) in a group of older schizophrenia patients and related them to cognitive and MRI measures. Older schizophrenia (n = 11), AD patients (n = 20) and elderly controls (n = 6) underwent cognitive testing, lumbar puncture, and MRI scanning. Abeta42 and total and p-tau concentrations were assayed in the CSF. MRI volumes were assessed using both voxel-based (cortical pattern matching) and region-of-interest analyses. RESULTS: CSF tau concentration in older schizophrenia patients was within normal limits (total tau 171 ± 51 pg/ml, p-tau 32 ± 8 pg/ml), while CSF Abeta42 (465 ± 112 pg/ml) levels were significantly lower compared to healthy elders (638 ± 130 pg/ml) but higher than in AD patients (352 ± 76 pg/ml). There was a strong positive relationship between CSF total or p-tau levels and MMSE scores in schizophrenia patients but not in AD, where higher concentrations of total tau were correlated with higher volumes in the occipital cortex (r = 0.63, p = 0.036), while in AD a significant correlation was found between lower Abeta42 concentrations and lower gray matter volume in the cingulate and lateral orbital cortices (r > 0.46, p < 0.05). CONCLUSIONS: Older schizophrenia patients show a peculiar pattern of CSF Abeta42 and tau concentrations that relates to cognitive and structural markers but is not consistent with neurodegeneration and could be secondary to neurodevelopmental or drug treatment effects.

Hippocampal and amygdalar volume changes in elderly patients with Alzheimer's disease and schizophrenia.

Patients with Alzheimer's disease (AD) and schizophrenia display cognitive, behavioural disturbances and morphological abnormalities. Although these latter reflect progressive neurodegeneration in AD, their significance in schizophrenia is still unclear. We explored the patterns of hippocampal and amygdalar atrophy in those patients and their associations with clinical parameters. Structural magnetic resonance imaging was performed in 20 elderly schizophrenia patients, 20 AD and 19 healthy older controls. Hippocampal and amygdalar volumes were obtained by manual segmentation with a standardized protocol and compared among groups. In both schizophrenia and AD patients, left hippocampal and amygdalar volumes were significantly smaller. The hippocampus/amygdala ratio was significantly lower in schizophrenia compared to both AD cases [2.4 bilaterally, 95% C.I. 2.2 to 2.7] and healthy controls bilaterally [2.5, 95% C.I. 2.3 to 2.9 in left and 2.7, 95% C.I. 2.4 to 3.1 in right hemisphere]. In schizophrenia patients, a significant positive correlation was found between age at disease onset and the right hippocampus/amygdala volume ratio (Spearman rho=0.56). Negative symptoms correlated with higher right/left amygdala volume ratio (Spearman's rho=0.43). Our data show that unlike AD, the hippocampus/amygdala ratio is abnormally low and correlates with the age at onset in schizophrenia, being a neurodevelopmental signature of the disease.

Oxygen-ozone therapy for degenerative spine disease in the elderly: a prospective study.

We describe our experience of oxygen-ozone therapy to treat degenerative spine disease in the elderly. From April 2004 to March 2008 we selected 129 patients with CT and/or MR evidence of spondyloarthrosis and disc degeneration of the lumbar spine. All patients enrolled in the study had contraindications to the administration of commonly used analgesic and anti-inflammatory drugs.Oxygen-ozone therapy was given by CT-guided intraforaminal injection as the first treatment followed by 4 weekly paralumbar infiltrations on an outpatient basis. The full treatment lasted a month. Clinical outcome was assessed 3 months and 1 year after treatment. The good results obtained indicate that oxygen-ozone therapy is an ideal treatment with no side-effects in elderly patients with degenerative spine disease.

Metanalysis on the effectiveness of low back pain treatment with oxygen-ozone mixture: Comparison between image-guided and non-image-guided injection techniques.

Low back pain (LBP) is a common disorder affecting an increasing number of people worldwide, whose diagnosis is focused on the identification of triggering causes. First line therapy usually starts from conservative approaches, whereas second line treatments include a spectrum of minimally invasive techniques, before resorting to more invasive surgical approaches. Among minimally invasive techniques, percutaneous oxygen-ozone injections represent one of the most common and cost-effective procedures. Aim of this study is to provide a metanalysis on literature evidences on percutaneous oxygen-ozone injections, comparing image-guided to non-image-guided techniques for LBP treatment. Imaging-guided procedures showed better performances compared to non-image-guided techniques based only on anatomical landmarks, with higher therapeutic efficacy and lower age-related variability in clinical results.

Markers of Alzheimer's disease in a population attending a memory clinic.

BACKGROUND: New marker-based criteria for the diagnosis of Alzheimer's disease (AD) were recently proposed. We describe their operational translation in 144 consecutive patients referred to our Memory Clinic. METHODS: Visual ratings of hippocampal atrophy and of cortical glucose hypometabolism in magnetic resonance imaging and positron emission tomography, and concentrations of total tau and Abeta1-42 in cerebrospinal fluid were assessed in 12 patients with subjective memory complaints (SMCs) (Mini-Mental State Examination [MMSE] score, 28.0 +/- 1.1 [mean +/- SD]), 37 with mild cognitive impairment (MCI) (MMSE, 25.1 +/- 3.6), 55 with AD (MMSE, 21.1 +/- 3.5), and 40 with non-AD dementia (MMSE, 21.6 +/- 5.5). RESULTS: The sensitivity for AD of each individual biomarker was higher (65% to 87%) than for MCI (18% to 50%). Each biomarker's specificity for SMC and non-AD dementias was good to moderate (83% and 53%). Positivity for at least one marker increased the probability 38 times of belonging to the AD group (P < 0.0001). CONCLUSION: The new diagnostic criteria can be operationalized in clinical routines, but longitudinal studies of MCI patients will need to assess the criteria's prognostic value.

Medial temporal lobe atrophy and posterior atrophy scales normative values.

OBJECTIVES: The medial temporal lobe atrophy (MTA) and the posterior atrophy (PA) scales allow to assess the degree hippocampal and parietal atrophy from magnetic resonance imaging (MRI) scans. Despite reliable, easy and widespread employment, appropriate normative values are still missing. We aim to provide norms for the Italian population. METHODS: Two independent raters assigned the highest MTA and PA score between hemispheres, based on 3D T1-weighted MRI of 936 Italian Brain Normative Archive subjects (age: mean ±â€¯SD: 50.2 ±â€¯14.7, range: 20-84; MMSE>26 or CDR = 0). The inter-rater agreement was assessed with the absolute intraclass correlation coefficient (aICC). We assessed the association between MTA and PA scores and sociodemographic features and APOE status, and normative data were established by age decade based on percentile distributions. RESULTS: Raters agreed in 90% of cases for MTA (aICC = 0.86; 95% CI = 0.69-0.98) and in 86% for PA (aICC = 0.82; 95% CI = 0.58-0.98). For both rating scales, score distribution was skewed, with MTA = 0 in 38% of the population and PA = 0 in 52%, while a score ≥ 2 was only observed in 12% for MTA and in 10% for PA. Median denoted overall hippocampal (MTA: median = 1, IQR = 0-1) and parietal (PA: median = 0, IQR = 0-1) integrity. The 90th percentile of the age-specific distributions increased from 1 (at age 20-59) for both scales, to 2 for PA over age 60, and up to 4 for MTA over age 80. Gender, education and APOE status did not significantly affect the percentile distributions in the whole sample, nor in the subset over age 60. CONCLUSIONS: Our normative data for the MTA and PA scales are consistent with previous studies and overcome their main limitations (in particular uneven representation of ages and missing percentile distributions), defining the age-specific norms to be considered for proper brain atrophy assessment.

Association of blood pressure and genetic background with white matter lesions in patients with mild cognitive impairment.

Background. White matter lesions (WMLs) may contribute to cognitive deficits in patients with mild cognitive impairment (MCI), but their pathogenesis is complex. Fluctuations of blood pressure (BP) over 24 hours and genetic predisposition to develop vascular damage have been implicated. Methods. In 63 MCI patients 65 years old or older, BP was measured both clinically and with ambulatory BP monitoring. Patients were classified in two groups: no/very mild (n = 34) and mild to severe (n = 29) WMLs, based on a visual scale on magnetic resonance (mean age 71.8 +/- 4.7 vs 74.6 +/- 5.1, and female gender 53% vs 66%, respectively). The volume of WMLs was measured by a semi-automatic method, separately for periventricular caps and rim, periventricular confluent, subcortical punctate, and subcortical confluent. Polymorphisms of cystatin C (CST3) and cholesterol 24-hydroxylase (CYP46) genes, putative risk factors for cerebrovascular disease, were determined. Results. The prevalence of cerebrovascular risk factors was similar in the two MCI groups of different WML severity, as well as clinic and ambulatory BP. In patients with mild to severe, but not in those with no/very mild WMLs, the volume of periventricular confluent WMLs increased with increasing daytime systolic BP (regression coefficient.47, 95% confidence interval [CI],.13 to.71 vs.02, 95% CI, -.32 to.36, p =.003 for the difference between slopes). The volume of other WML subtypes was not associated with ambulatory BP. Participants carrying both CST3*B and CYP46*T alleles were overrepresented in the MCI group with mild to severe WMLs (43% vs 17%, p.03). Conclusions. BP and gene putative risk factors for cerebrovascular disease are differentially associated with WMLs in two MCI groups of different WML severity. WMLs might develop for the convergence of innate with acquired factors.

Effect of the XbaI polymorphism of estrogen receptor alpha on postmenopausal gray matter.

The frequent polymorphism XbaI (A351G) in the estrogen receptor alpha (ERalpha) gene has been associated with some postmenopausal pathologies' risk such as Alzheimer's disease (AD) or cognitive decline. In the present study, we explored whether the XbaI polymorphism leads to different gray matter volumes using voxel-based morphometry (VBM) on 20 magnetic resonance images of healthy postmenopausal women. Subjects carrying the less common XbaI/X allele were contrasted to non-carriers in groups well balanced by relevant confounding variables. The XbaI/X allele carriers displayed clusters ranging from 9 to 28% of tissue reductions in the cerebellar (cluster size, z, stereotactic coordinates: 16 mm(3); 3.17; 14, -94, -38) and cerebral cortex, in particular in the occipital lobe (272 mm(3); 3.76; -38,-68,-16), in the middle frontal gyrus (192 mm(3); 3.71; 38, 12, 38) and in the middle temporal gyrus, while the opposite comparison was negative. The XbaI/X allele in ERalpha gene is associated to smaller gray matter volumes of the cerebral and cerebellar cortex. This allele might increase the susceptibility for senile neurodegenerative conditions, being associated to smaller cerebral reserve.

The topography of grey matter involvement in early and late onset Alzheimer's disease.

Clinical observations have suggested that the neuropsychological profile of early and late onset forms of Alzheimer's disease (EOAD and LOAD) differ in that neocortical functions are more affected in the former and learning in the latter, suggesting that they might be different diseases. The aim of this study is to assess the brain structural basis of these observations, and test whether neocortical areas are more heavily affected in EOAD and medial temporal areas in LOAD. Fifteen patients with EOAD and 15 with LOAD (onset before and after age 65; Mini Mental State Examination 19.8, SD 4.0 and 20.7, SD 4.2) were assessed with a neuropsychological battery and high-resolution MRI together with 1:1 age- and sex-matched controls. Cortical atrophy was assessed with cortical pattern matching, and hippocampal atrophy with region-of-interest-based analysis. EOAD patients performed more poorly than LOAD on visuospatial, frontal-executive and learning tests. EOAD patients had the largest atrophy in the occipital [25% grey matter (GM) loss in the left and 24% in the right hemisphere] and parietal lobes (23% loss on both sides), while LOAD patients were remarkably atrophic in the hippocampus (21 and 22% loss). Hippocampal GM loss of EOAD (9 and 16% to the left and right) and occipital (12 and 14%) and parietal (13 and 12%) loss of LOAD patients were less marked. In EOAD, GM loss of 25% or more was mapped to large neocortical areas and affected all lobes, with relative sparing of primary sensory, motor, and visual cortex, and anterior cingulate and orbital cortex. In LOAD, GM loss was diffusely milder (below 15%); losses of 15-20% were confined to temporoparietal and retrosplenial cortex, and reached 25% in restricted areas of the medial temporal lobe and right superior temporal gyrus. These findings indicate that EOAD and LOAD differ in their typical topographic patterns of brain atrophy, suggesting different predisposing or aetiological factors.

Brain perfusion correlates of medial temporal lobe atrophy and white matter hyperintensities in mild cognitive impairment.

OBJECTIVE: To assess the association of Medial Temporal lobe Atrophy (MTA) and White Matter Hyperintensities (WMHs) with gray matter perfusion in Mild Cognitive Impairment (MCI). METHODS: 56 MCI patients (age = 69.3 +/- 7.0, 32 females) underwent brain MR scan and (99m)Tc ECD SPECT. We evaluated MTA according to Scheltens' fivepoint scale on T1 MR images, and assessed WMHs using the rating scale for age-related white matter changes on T2-weighted and FLAIR MR images. We divided MCI into age-matched subgroups with high and low MTA and high and low WMHs load. We processed SPECT images with SPM2 following an optimized protocol and performed a voxel-based statistical analysis comparing high vs. low MTA and high vs. low WMHs, setting p-value at 0.001 uncorrected, thresholding cluster extent at 100 voxels, using proportional scaling and entering age and WMHs or MTA respectively as nuisance covariates. RESULTS: MCI with high compared with low MTA showed hypoperfusion in the left hippocampus and in the left parahippocampal gyrus. MCI with high compared with low WMHs showed a hypoperfusion area in the left insular region and superior temporal gyrus. CONCLUSIONS: MTA in MCI is associated with hippocampal gray matter hypoperfusion while WMHs is associated with gray matter hypoperfusion in areas of the insula and temporal neocortex. These results confirm that MTA is associated with local functional changes and suggest that WMHs may be associated with remote brain cortical dysfunction.

Effects of hormone therapy on brain morphology of healthy postmenopausal women: a Voxel-based morphometry study.

OBJECTIVE: Estrogens are known to be protective in age-associated cognitive changes in humans and in neurodegeneration in animal models. The aim of this study was to evaluate the potential effects of estrogen therapy (ET) on human gray matter volume in vivo. DESIGN: Forty healthy postmenopausal women underwent three-dimensional high-resolution magnetic resonance imaging: 17 were never treated, 16 were currently receiving ET, and 7 had had ET in the past. Voxel-based morphometry (VBM) with SPM2 was used, according to an optimized protocol, to compare women under past and current ET to those never treated. Significance threshold was set at P = 0.01, corrected by false discovery rate. RESULTS: Voxel-based morphometry indicated that estrogen use was associated with greater gray matter volumes in the whole group of treated women, which included the cerebellum (cluster size, Z coordinates: 5,527; 5.15; -14 -54 -10), the amygdaloid-hippocampal complex (left: 19; 3.55; -22 -4 -18; right: 45; 3.61; 16 -6 -16), and extended to the frontal, temporal, parietal, and occipital neocortex. The comparison current ET versus past ET use showed that women who underwent treatment in the past had greater volumes of gray matter compared to women under current treatment. CONCLUSIONS: ET might slow down age-related gray matter loss in postmenopausal women. The structures that exhibited greater volume in association with ET included the cerebellar and cerebral cortices and, typically involved in Alzheimer's disease, the medial temporal structures and the temporoparietal junction.