Showing papers by "Giovanni B. Frisoni published in 2005"

A voxel based morphometry study on mild cognitive impairment.

Abstract: Background: Mild cognitive impairment (MCI) is the most widely used concept in classifying cognitive impairment in the elderly who do not fulfil the criteria for dementia. MCI is considered to confer an increased risk of progressing to dementia and most often Alzheimer's disease (AD). Various approaches such as imaging of the brain have been applied to predict the conversion of MCI to dementia. A number of volumetric magnetic resonance imaging (MRI) studies have detected atrophy of the medial temporal lobe in subjects with MCI, but for the other cerebral regions the results have been inconsistent. Objective: To study the pattern of brain atrophy in MCI. Methods: Thirty two controls and 51 individuals with MCI deriving from population based cohorts were studied by MRI using voxel based morphometry. The threshold of t maps was set at p<0.001. Results: Individuals with MCI had significant unilateral atrophy in the medial temporal lobe on the right side. Less extensive atrophy was found elsewhere—for example, in the temporal lobe, left superior parietal lobule, left anterior cingulate gyrus, and bilaterally in the thalami. Conclusions: The MRI findings in MCI resemble those seen in early AD.

Structural correlates of early and late onset Alzheimer's disease: voxel based morphometric study.

Abstract: Objective: To examine the brain structural correlates of age at onset in patients with Alzheimer’s disease. Methods: We studied nine patients with early onset (age ⩽65 years), nine with late onset (age >65) Alzheimer’s disease (EOAD and LOAD, respectively) of mild-moderate severity, and 26 controls who were stratified into younger (YC, age ⩽65, n = 9) and older (OC, age >65, n = 17) subjects. The patients were closely matched for clinical severity: 3/2/3/1 patients had clinical dementia rating of 0.5/1/2/3, respectively, in both the groups. High resolution magnetic resonance images of the brain of the EOAD and YC groups and the LOAD and OC groups were compared on a voxel by voxel basis with statistical parametric mapping to detect areas specifically atrophic. Results: The patients with EOAD showed greater neocortical atrophy at the temporoparietal junction while the patients with LOAD showed greater hippocampal atrophy. The results could not be accounted for by the apolipoprotein E genotype. Conclusions: Since genetic factors are believed to play a relevant pathogenetic role in EOAD and environmental factors in LOAD, genetic and environmental factors may differentially predispose the neocortical and limbic areas to the development of Alzheimer’s neuropathology.

Reality orientation therapy combined with cholinesterase inhibitors in Alzheimer's disease: randomised controlled trial

Abstract: Background Reality orientation therapy combined with cholinesterase inhibitors has not been evaluated in patients with Alzheimer’s disease. Aims To perform such an evaluation. Method We randomly assigned 79 of156 patients treated with donepezil to receive a reality orientation programme. Caregivers of the treatment group were trained to offer the programme at home 3 days a week, 30 min/day, for 25 consecutive weeks, and were invited to stimulate and involve patients in reality-based communication. Results The treatment group showed a slight improvement in Mini-Mental State Examination (MMSE) scores (mean change +0.2, s.e.=0.4) compared with a decline in the control group (mean change –1.1, s.e.=0.4; P =0.02). Similarly for the Alzheimer’s Disease Assessment Scale – Cognition (treatment group mean change +0.4, s.e.=0.8; control group –2.5, s.e.=0.8; P =0.01). The intervention had an equal effecton cognition in those with mild (MMSE score ≥ 20) and moderate (score <20) dementia. No significant effect was observed for behavioural and functional outcomes. Conclusions Reality orientation enhances the effects of donepezil on cognition in Alzheimer’s disease.

Relationship Between Functional Loss Before Hospital Admission and Mortality in Elderly Persons With Medical Illness

Abstract: Objective. This hospital-based prospective study tests the hypothesis that, in a large group of hospitalized elderly patients, those who report functional decline between pre-illness baseline and hospital admission have a higher risk of death. Methods. Nine hundred fifty elderly ambulant patients (F ¼ 69.3%; mean age 78.3 6 8.5 years) were consecutively admitted to a geriatric ward (Poliambulanza Hospital, Brescia, Italy) during a 15-month period. Number and severity of somatic diseases, Charlson Index score, APACHE II score, level of serum albumin, cognitive status (by Mini-Mental State Examination), and depression score (by Geriatric Depression Scale), were assessed on admission and evaluated as potential prognostic factors. Functional status (by Barthel Index) was assessed by self-report on admission. Preadmission function was also assessed by self-report at the time of admission. Impairment of function due to an acute event is measured as the difference between performances on admission and 2 weeks before the acute event. Six-month survival was the main outcome variable. Results. Factors related to mortality in bivariate analysis were: male sex, age over 80, cancer, congestive heart failure, pulmonary diseases, elevated Charlson Index score, and (independently) dementia (Mini-Mental State Examination , 18), APACHE–Acute Physiology Score , albumin level ,3.5 g/dL, and anemia. After controlling for these variables and for Barthel Index score 2 weeks before the acute event, change in function due to the acute disease is independently related to 6-month mortality (minor functional change [,30 Barthel Index Point] relative risk: 1.3, 95% confidence interval, 0.6–3.0 and major functional change [major functional decrement] relative risk: 2.8, 95% confidence interval, 1.3–5.7). Conclusions. Disease-induced disability may reflect a condition of biological inability to react to acute diseases (i.e., frailty), and should be assessed as a relevant prognostic indicator.

Insulin resistance in cognitive impairment: the InCHIANTI study.

Abstract: Objective To test the association between cognitive impairment, with and without subcortical features, and insulin resistance in an elderly community-dwelling population. Design Cross-sectional wave of an epidemiologic longitudinal study (InCHIANTI). Participants A total of 523 people, aged 70 to 90 years without diabetes mellitus or hyperglycemia, from the InCHIANTI cohort were included in the study. A total of 119 individuals had cognitive impairment (Mini-Mental State Examination [MMSE] score Results The insulin resistance profile of patients in the CI/SF+ group was similar to that of individuals who had experienced stroke, whereas the profile of individuals with cognitive impairment without subcortical features (CI/SF− group) was similar to that of individuals in the no CI group. Patients in the CI/SF− group showed insulin resistance comparable to individuals in the no CI group (age-adjusted P = .27, .19, and .64, respectively, for difference in fasting blood insulin level, HOMA-IR, and QUICKI in linear regression models) and lower than patients with stroke (age-adjusted P = .01, .02, and .07, respectively). On the contrary, patients in the CI/SF+ group had insulin resistance and sensitivity values similar to those of the stroke group (age-adjusted P = .80, .84, and .75, respectively, for difference in fasting blood insulin level, HOMA-IR, and QUICKI) but significantly different from those in the no CI group (age-adjusted P = .01, .03, and .02, respectively). Conclusions Cognitive impairment with but not without subcortical features is associated with biochemical and clinical features of insulin resistance syndrome. In epidemiologic populations, insulin resistance might contribute to cognitive impairment through a vascular mechanism.

Distinctive clinical features of mild cognitive impairment with subcortical cerebrovascular disease

Abstract: Background and Purpose: Patients with mild cognitive impairment and subcortical cerebrovascular disease (svMCI) can be isolated using criteria modified from those of Erkinjuntti et

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

Abstract: 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.

Brain volumes in healthy adults aged 40 years and over: a voxel-based morphometry study.

Abstract: Background and aims: Gender and age effect on brain morphology have been extensively investigated. However, the great variety in methods applied to morphology partly explain the conflicting results of linear patterns of tissue changes and lateral asymmetry in men and women. The aim of the present study was to assess the effect of age, gender and laterality on the volumes of gray matter (GM) and white matter (WM) in a large group of healthy adults by means of voxel-based morphometry. This technique, based on observer-independent algorithms, automatically segments the 3 types of tissue and computes the amount of tissue in each single voxel. Methods: Subjects were 229 healthy subjects of 40 years of age or older, who underwent magnetic resonance (MR) for reasons other than cognitive impairment. MR images were reoriented following the AC-PC line and, after removing the voxels below the cerebellum, were processed by Statistical Parametric Mapping (SPM99). GM and WM volumes were normalized for intracranial volume. Results: Women had more fractional GM and WM volumes than men. Age was negatively correlated with both fractional GM and WM, and a gender × age interaction effect was found for WM, men having greater WM loss with advancing age. Pairwise differences between left and right GM were negative (greater GM in right hemisphere) in men, and positive (greater GM in left hemisphere) in women (−0.56±4.2 vs 0.99±4.8; p=0.019). Conclusions: These results support side-specific accelerated WM loss in men, and may help our better understanding of changes in regional brain structures associated with pathological aging.

Alzheimer's disease-associated disability: an ICF approach.

Abstract: Purpose. The aim of the study is to provide a description of dementia-associated disability in Alzheimer's disease (AD) patients through the International Classification of Functioning, Disability and Health (ICF).Method. Twenty-six AD patients at different stages of disease participated in the study. Mini Mental State Examination (MMSE) and Global Deterioration Scale (GDS) were used to stage the degree of cognitive impairment and the stage of disease, respectively. All subjects were classified using the ICF categories in the more detailed four-level version. Correlation between compromised ICF items and both MMSE and GDS scores were calculated through Spearman Rho test.Results. Mental functions were impaired in all the subjects examined. Data on activity and participation showed that not only domestic life, self care, and mobility but also communication and interaction and social relationships are compromised in AD patients. Three main areas appeared as the most relevant facilitators: products and techno...

Predicting clinical variable from MRI features: application to MMSE in MCI

Abstract: The ability to predict a clinical variable from automated analysis of single, cross-sectional T1-weighted (T1w) MR scans stands to improve the management of patients with neurological diseases. We present a methodology for predicting yearly Mini-Mental Score Examination (MMSE) changes in Mild Cognitive Impairment (MCI) patients. We begin by generating a non-pathological, multidimensional reference space from a group of 152 healthy volunteers by Principal Component Analyses of (i) T1w MR intensity of linearly registered Volumes of Interest (VOI); and (ii) trace of the deformation fields of nonlinearly registered VOIs. We use multiple regression to build linear models from eigenvectors where the projection eigencoordinates of patient data in the reference space are highly correlated with the clinical variable of interest. In our cohort of 47 MCI patients, composed of 16 decliners, 26 stable and 5 improvers (based on MMSE at 1 yr follow-up), there was a significant difference (P = 0.0003) for baseline MMSE scores between decliners and improvers, but no other differences based on age or sex. First, we classified our three groups using leave-one-out, forward stepwise linear discriminant analyses of the projection eigencoordinates with 100% accuracy. Next, we compared various linear models by computing F-statistics on the residuals of predicted vs actual values. The best model was based on 10 eigenvectors + baseline MMSE, with predicted yearly changes highly correlated (r = 0.6955) with actual data. Prospective study of an independent cohort of patients is the next logical step towards establishing this promising technique for clinical use.

Pathological validation of a CT-based scale for subcortical vascular disease. The OPTIMA Study.

Abstract: The validity of a computed tomography (CT)-based rating scale that separately rates leukoaraiosis, patchy lesions, and lacunes was tested using neuropathological findings collected on 87 subjects enrolled in the Oxford Project to Investigate Memory and Ageing. The CT-based score (range 0–64) was associated with both small vessel disease (p = 0.015) and microinfarcts (p = 0.002) on pathology. A sum score of subcortical cerebrovascular disease (CVD) on pathology was computed, 0 indicating absent/mild small vessel CVD and no microinfarcts, 1 moderate small vessel CVD or microinfarcts, and 2 and higher both conditions or severe small vessel CVD. Subjects with a sum score of 0 were decreasing with increasing severity of CT-based score (64, 46, and 25% in those with CT-based scores of 0, 1–38, and 39 and higher), while those with a sum score of 2 and higher were increasing (0, 14, and 44%; p = 0.002). A standardized assessment of subcortical CVD on CT films can be compounded into a unique score that is in good agreement with neuropathology. This supports the validity of the CT-based visual rating scale as a valid tool to detect subcortical vascular changes in elderly persons.

Multiple Sclerosis and Alzheimer Disease through the Looking Glass of MR Imaging

Abstract: MR imaging has led to a profound shift of perspective in many central nervous system conditions. In epilepsy, quantitative evidence of hippocampal volume loss by MR imaging has been highly correlated with seizure onset in medial temporal structures ([1][1]); in stroke, it has enabled detection of

Prescription and choice of diagnostic imaging by physician specialty in Alzheimer’s Centers (Unità di Valutazione Alzheimer — UVA) in Northern Italy

Abstract: Background and aims: Physician’s specialty has been shown to have an effect on health outcomes and financial expenditure in a number of conditions. This is particularly true in the differential diagnosis of cognitive deterioration, in which technological procedures are needed. The aim of this study is to assess the effect of physician specialty on the prescription of diagnostic imaging (CT and MR) in patients with cognitive impairment, referred to Alzheimer Evaluation Units (Unita di Valutazione Alzheimer] in Northern Italy. Methods: An ad-hoc questionnaire was sent to UVA referents in northern Italy (Lombardy, Piedmont, Trentino, Emilia-Romagna and Veneto), requesting information on the frequency of prescriptions for CT and MR and reasons for the choice, on a 0 to 7 scale. Results: The physician-in-charge was a neurologist in 22 and a geriatrician in 22 Alzheimer’s centers. Intensive use of CT was similar in neurologists and geriatricians (64 vs 68%], whereas intensive use of MR was more frequent in neurologists (41 vs 10%; p=0.03). Overall, organizational factors (availability of the scanner on-site and waiting list for imaging, mean weight=1.6±1.4) were as important as patient-related factors (age, severity of cognitive impairment, and clinical suspicion of cerebrovascular disease, mean weight 1.1±1.4; p=0.84). Sixty-five percent of neurologists based their choices between CT and MR on patient-related and 35% on organizational factors, whereas the opposite proportion was found for geriatricians (29 vs 71%, p=0.04). Conclusions: The high weight of organizational factors on the prescription of diagnostic imaging is not consistent with an evidence-based diagnostic system.

Structural correlates of early and late onset Alzheimer's disease: voxel based morphometric study. Commentary

Abstract: Objective: To examine the brain structural correlates of age at onset in patients with Alzheimer's disease. Methods: We studied nine patients with early onset (age ≤65 years), nine with late onset (age >65) Alzheimer's disease (EOAD and LOAD, respectively) of mild-moderate severity, and 26 controls who were stratified into younger (YC, age 65, n=17) subjects. The patients were closely matched for clinical severity: 3/2/3/1 patients had clinical dementia rating of 0.5/1/2/3, respectively, in both the groups. High resolution magnetic resonance images of the brain of the EOAD and YC groups and the LOAD and OC groups were compared on a voxel by voxel basis with statistical parametric mapping to detect areas specifically atrophic. Results: The patients with EOAD showed greater neocortical atrophy at the temporoparietal junction while the patients with LOAD showed greater hippocampal atrophy. The results could not be accounted for by the apolipoprotein E genotype. Conclusions: Since genetic factors are believed to play a relevant pathogenetic role in EOAD and environmental factors in LOAD, genetic and environmental factors may differentially predispose the neocortical and limbic areas to the development of Alzheimer's neuropathology.

Neuroimaging services on the net

Abstract: The present paper reports a research project aimed at developing a cluster of clinical Institutions to share data and expertise in the fields of computational neuroanatomy. In particular, our first results concern a network system to transfer magnetic resonance (MR) images, explore and use Voxel-Based Morphometry (VBM)-based reports in four remote clinical settings. The cluster is composed of a central unit for the recording and processing of MR images, and peripheral federated units. The former is LENITEM -Lab of Epidemiology, Neuroimaging and TEleMedicine- Brescia, Italy; the latter are clinical units usually treating patients with neurodegenerative diseases. The cluster is meant to be grounded on a network infrastructure, providing services to the units: the first service to be designed and realised is VBM. The peripheral (client) units transfer MR images to the central one; here they are processed and analysed; a VBM-based report is made available, within a few hours, to the client unit. Neuroimaging techniques give rise to network services provided on demand.