Clinical and medial temporal features in a family with mood disorders.

It is debated whether non-affected relatives of patients with affective disorders share a specific brain structure endophenotype. Aim of this work is to explore the medial temporal morphology in affected and non-affected members of a family with mood disorders. Hippocampi and amygdalae were manually traced from the 3D magnetic resonance imaging of five affected family members, 10 non-affected relatives, and 15 unrelated matched controls. Affected and non-affected relatives were characterized by larger left amygdalae (18%, p=0.030), smaller right hippocampus (up to 18%, p<0.0005), and reduced hippocampal asymmetry (p<0.001) than controls. Abnormal, albeit non significant, positive correlations of MTL volumes with age were observed, with the exception of smaller volume of the left hippocampus with advancing age (r=-0.76) in the affected relatives. These data add to the evidence that abnormal medial temporal structures may constitute an endophenotype for affective disorders.

Cortical sources of resting EEG rhythms in mild cognitive impairment and subjective memory complaint.

Are cortical electroencephalographic (EEG) rhythms altered in amnesic and non-amnesic mild cognitive impairment (MCI), subjective memory complaint (SMC), and healthy elderly (Nold) subjects? Eyes-closed resting EEG was recorded in 79 Nold, 53 SMC, 51 non-amnesic MCI, and 92 amnesic MCI subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz) and gamma (30-40 Hz). Cortical EEG sources were estimated by standardized low resolution brain electromagnetic tomography (sLORETA). Results showed that (i) the frontal delta sources were greater in amplitude in the amnesic MCI and SMC subjects than in the Nold subjects (p<0.05-0.01); (ii) the parietal and occipital theta sources were lower in amplitude in the SMC subjects than in the Nold subjects (p<0.046); (iii) the occipital theta sources were greater in amplitude in the amnesic MCI subjects than in the SMC and non-amnesic MCI subjects (p<0.02-0.01); (iv) the parietal and occipital alpha 1 sources were greater in amplitude in the Nold subjects than in the SMC, non-amnesic MCI and amnesic MCI subjects (p<0.00001); (v) the central alpha 1 sources were lower in amplitude in the SMC subjects than in the non-amnesic MCI subjects (p<0.002); (vi) the occipital alpha 1 sources were greater in amplitude in the SMC subjects than in the amnesic MCI subjects (p<0.0003); (vii) the parietal and occipital alpha 2 sources were greater in amplitude in the Nold subjects than in the non-amnesic MCI subjects (p<0.041-0.0004); (viii) the occipital alpha 2 sources were greater in the SMC subjects than in the non-amnesic MCI subjects (p<0.02). These results suggest that amnesic MCI and SMC subjects present some of the typical alterations of brain neural synchronization as revealed by resting cortical EEG rhythms in Alzheimer's disease patients.

The Italian Brain Normative Archive of structural MR scans: norms for medial temporal atrophy and white matter lesions.

BACKGROUND AND AIMS: To describe the clinical and neuropsychological features of a large group of cognitively intact persons subjected to brain high-resolution magnetic resonance (MR), to compare them with the general population, and to set norms for medial temporal atrophy and white matter lesions. METHODS: Participants in the Italian Brain Normative Archive (IBNA) study were 483 consecutive volunteers undergoing MR for reasons unrelated to cognition (migraine or headache, visual and balance or auditory disturbances, paresthesias, and others) and showing no brain damage. Manual tracing of hippocampal and amygdalar volumes and visual rating of white matter lesions were made. The whole study group was stratified by age (

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.

Clinical and neuropsychological features associated with structural imaging patterns in patients with mild cognitive impairment.

AIM: To describe the clinical and neuropsychological features of mild cognitive impairment (MCI) patients with medial temporal atrophy (MTA), white matter hyperintensities (WMH), both, and neither and to assess whether the rate of progression differs among groups. METHODS: Ninety-five MCI patients were divided into 4 groups based on the presence of MTA and WMH: 29 were MTA- WMH-, 11 MTA- WMH+, 23 MTA+ WMH-, and 32 MTA+ WMH+. MCI patients were compared with 30 normal subjects. MTA and WMH were assessed with MR-based visual rating scales. Subjects underwent an extensive clinical and neuropsychological investigation. Fifty-six underwent follow-up evaluation. RESULTS: MTA- WMH- had relatively good neuropsychological performance, little vascular and physical comorbidity. MTA- WMH+ performed poorly only on executive neuropsychological tests. MTA+ WMH- patients had poor neuropsychological performances (mainly on memory tests), high physical and vascular comorbidity. MTA+ WMH+ were impaired in neuropsychological performances, had a high number of physical diseases and severe vascular comorbidity. On follow-up, 25% of MTA+ WMH- and 32% of MTA+ WMH+ and none in MTA- WMH- and in MTA- WMH+ converted to dementia (p = 0.05, log rank test). CONCLUSION: Structural neuroimaging can identify subgroups of MCI patients with specific clinical and neuropsychological features.

Frontal white matter volume and delta EEG sources negatively correlate in awake subjects with mild cognitive impairment and Alzheimer's disease.

OBJECTIVE: A relationship between brain atrophy and delta rhythmicity (1.5-4 Hz) has been previously explored in Alzheimer's disease (AD) subjects [Fernandez A, Arrazola J, Maestu F, Amo C, Gil-Gregorio P, Wienbruch C, Ortiz T. Correlations of hippocampal atrophy and focal low-frequency magnetic activity in Alzheimer disease: volumetric MR imaging-magnetoencephalographic study. Am J Neuroradiol. 2003 24(3):481-487]. In this study, we tested the hypothesis that such a relationship does exist not only in AD patients but also across the continuum of subjects with mild cognitive impairment (MCI) and AD. METHODS: Resting, eyes-closed EEG data were recorded in 34 MCI and 65 AD subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by LORETA. Cortical EEG sources were correlated with MR-based measurements of lobar brain volume (white and gray matter). RESULTS: A negative correlation was observed between the frontal white matter and the amplitude of frontal delta sources (2-4 Hz) across MCI and AD subjects. CONCLUSIONS: These results confirmed for the first time the hypothesis that the sources of resting delta rhythms (2-4 Hz) are correlated with lobar brain volume across MCI and AD subjects. SIGNIFICANCE: The present findings support, at least at group level, the 'transition hypothesis' of brain structural and functional continuity between MCI and AD.

Visual assessment of medial temporal atrophy on MR films in Alzheimer's disease: comparison with volumetry.

BACKGROUND AND AIMS: To test the agreement of a visual rating scale of medial temporal lobe atrophy (MTA) with linear and volumetric assessments, and to test its accuracy in discriminating between Alzheimer's disease (AD) patients and controls. METHODS: Participants were 28 patients with AD and 29 healthy controls. MTA was evaluated according to Scheltens' five-point scale. Its accuracy in distinguishing AD patients from controls was evaluated as a stand-alone measure and in association with linear [width of the temporal horn (WTH)] and volumetric [hippocampal volume (HV)] measures. RESULTS: The agreement of this visual rating scale with the other MTA measures was statistically significant (vs WTH and vs HV, p for trend < 0.00005). The visual rating scale showed a good accuracy in distinguishing AD patients from controls [area under the curve (AUC) 0.89, 95% confidence interval (CI) 0.79-0.98]. Although the accuracy of the visual rating scale improved in association with linear WTH (AUC 0.91, 95% CI 0.82-0.99) and in association with HV (AUC 0.93, 95% CI 0.86-1.00), the improvement was not significant. CONCLUSIONS: The visual rating scale of MTA, easily applicable in clinical practice, shows good agreement with more demanding quantitative methods, and can discriminate AD patients from controls with good accuracy.

The MRI pattern of frontal and temporal brain atrophy in fronto-temporal dementia.

OBJECTIVE: To compare patterns of brain atrophy in fronto-temporal dementia (FTD) and Alzheimer's disease (AD) since atrophy in individual areas may not be sufficiently specific as diagnostic marker. METHODS: Frontal, temporal and hippocampal atrophy was measured from MRI of 10 FTD patients, 27 AD, and 27 controls. Corrected atrophy and asymmetry were computed (W-scores). RESULTS: FTD had mild atrophy in the hippocampus (average W-score=-1.3), severe in the frontal (W-score=-2.4) and very severe in the temporal lobes (W-score=-2.9). AD had moderate atrophy in the hippocampus and temporal lobes (W-score=-1.8 and -1.9, respectively), and very mild frontal atrophy (W-score=-0.9). Atrophy was more asymmetrical in FTD (left more atrophic) than in AD patients, particularly in the temporal lobes. A discriminant function including the asymmetry values of frontal and temporal regions could separate FTD from AD with 90% sensitivity and 93% specificity. CONCLUSIONS: FTD is characterized by a specific pattern of atrophy, more useful than atrophy of single regions in the differential diagnosis.

Clinical characteristics of frontotemporal patients with symmetric brain atrophy.

In this paper we explored patterns of frontal and temporal asymmetry in frontotemporal dementia (FTD) and tried to isolate clinical correlates associated with asymmetry or lack thereof. Volumes of frontal and temporal lobes, hippocampus and entorhinal cortex were measured using magnetic resonance imaging (MRI) in 10 patients with FTD. Age- and cranial size-specific values were computed through linear regression analysis (W-scores). A subgroup of 3 patients with symmetric frontal and temporal atrophy was identified. When compared to patients with asymmetric atrophy, the former had younger age at onset of the disease (p = 0.02), greater overall frontotemporal (p = 0.02) and greater entorhinal atrophy (p < 0.04). Two of the three patients were apolipoprotein E epsilon4 carriers versus none of the asymmetric patients (p = 0.02). The lack of asymmetry in this small sample of FTD patients was associated with greater brain atrophy, younger age at onset, and presence of the epsilon4 allele of apolipoprotein E. The presence of the epsilon4 allele is consistent with the hypothesis of greater vulnerability of the brain in epsilon4 carriers.

Mild cognitive impairment with subcortical vascular features: clinical characteristics and outcome.

OBJECTIVES: To identify non-demented individuals with cognitive impairment due to a cerebrovascular etiology among those coming to observation of a memory clinic and to describe their clinical features and outcome. METHODS: Patients were enrolled in a prospective study on early cognitive impairment carried out in a Memory Clinic. Mild cognitive impairment of the vascular type (MCI-V) was defined based on modified criteria for subcortical vascular dementia (SVD) by Erkinjuntti and colleagues. Twenty-nine patients with MCI-V (age 78 +/- 7, Mini Mental State Exam (MMSE) 24 +/- 3) were compared with 14 with mild cognitive impairment of degenerative etiology (MCI) based on the Mayo Clinic criteria (age 72 +/- 9, MMSE 25 +/- 2), and to 21 patients with frank SVD (age 80 +/- 6, MMSE 21 +/- 3). Patients were followed over time for 32 +/- 8 months. RESULTS: MCI-V patients had a neuropsychological profile characterized by poor performance on frontal tests (Wisconsin card sorting and word fluency) and neurological features of parkinsonism without tremor (impairment of balance and gait). Of those followed for at least 40 months, 50 % of patients with MCI-V and SVD had died, while all MCI patients were still alive ( P = 0.03). Of those alive, 68 % of the MCI-V, 52 % of the SVD, and 17 % of the MCI patients had reached one of the following outcomes at 40 months: nursing home placement, functional loss, and cognitive deterioration ( P = 0.02). CONCLUSIONS: Patients with MCI-V have a distinctive clinical picture and can be identified in a clinical setting. Because of the high frequency of adverse outcomes, very early preventive measures need to be devised.

Regional brain atrophy in patients with mild Alzheimer's disease and delusions.

BACKGROUND AND OBJECTIVE: The pathophysiology and the neurobiology of the behavioral disturbances in Alzheimer's disease (AD) are far from understood. The aim of the study was to assess whether delusional AD patients have a specific pattern of regional brain atrophy. METHODS: The setting of the study was the outpatient facility of a memory clinic. Subjects were 41 AD patients with mild dementia severity (Mini-Mental State Exam score of 22 +/- 3, range 18 to 27). Delusions were assessed with the pertinent subscale of the UCLA Neuropsychiatric Inventory (NPI). Nondelusional (n = 22) AD and delusional (n = 19) AD were defined on the basis of absence (NPI delusions subscale = 0) or presence (NPI delusions subscale = 1 or higher) of delusions. Thirteen (68%) of the delusional patients had isolated theft delusions, and 6 (32%) had theft associated with another paranoid delusion (of jealousy or persecution). None of the patients had misidentifications or other delusions of nonparanoid content. Temporal lobe and frontal lobe atrophy were assessed with linear measures (radial width of the temporal horn, rWTH, and frontal index, FI) taken from computed tomographic films. Temporal and frontal asymmetries were computed as right/left ratio of the rWTH and FI. RESULTS: AD patients without delusions had symmetrical enlargement of both temporal (8.1 +/- 3.9 vs. 8.5 +/- 4.5) and frontal horns (35.8 +/- 4.8 vs. 35.9 +/- 4.6). On the contrary, AD with delusions showed temporal horns larger to the right (9.1 +/- 3.3 vs. 7.7 +/- 3.1, p = .06) and the frontal horn to the left (35.7 +/- 4.3 vs. 37.5 +/- 4.2, p = .02). This different pattern was confirmed with a gender-adjusted repeated measures analysis of variance model interaction term between asymmetry and group: F1,38 = 5.5, p = .03). DISCUSSION: AD patients with delusions are characterized by a specific pattern of frontal and temporal asymmetry of brain atrophy, whereas nondelusional patients are symmetric. Because the asymmetry pattern of the delusional patients is similar to the physiological pattern of asymmetry of individuals without dementia, the data indicate that the absence of theft delusions in the mild stage of AD rather than their presence is associated with an abnormal asymmetry pattern.