Showing papers by "Giovanni B. Frisoni published in 2006"
TL;DR: Identifying patients at a high risk for progression to dementia and establishing more specific and adapted therapeutic strategies at an early stage, together with more structured overall management, is made possible by the diagnostic procedure proposed.
Abstract: Mild cognitive impairment (MCI) was proposed as a nosological entity referring to elderly people with mild cognitive deficit but no dementia. MCI is a heterogeneous clinical entity with multiple sources of heterogeneity. The concept of MCI was reviewed and a diagnostic procedure with three different stages was proposed by the European Consortium on Alzheimer's Disease Working Group on MCI. Firstly, MCI should correspond to cognitive complaints coming from the patients or their families; the reporting of a relative decline in cognitive functioning during the past year by a patient or informant; cognitive disorders as evidenced by clinical evaluation; absence of major repercussions on daily life; and absence of dementia. These criteria, similar to those defined during an international workshop in Stockholm, make it possible to identify an MCI syndrome, which is the first stage of the diagnostic procedure. Secondly, subtypes of MCI had to be recognised. Finally, the aetiopathogenic subtype could be identified. Identifying patients at a high risk for progression to dementia and establishing more specific and adapted therapeutic strategies at an early stage, together with more structured overall management, is made possible by the diagnostic procedure proposed.
573 citations
TL;DR: Functional data on large populations support the 'transitional hypothesis' of a shadow zone across normality, pre-clinical stage of dementia (MCI), and AD.
268 citations
TL;DR: Can quantitative electroencephalography (EEG) predict the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD)?
246 citations
TL;DR: It is suggested that the occipital delta and posterior cortical alpha rhythms decrease in magnitude during physiological aging with both linear and nonlinear trends.
Abstract: This electroencephalographic (EEG) study tested whether cortical EEG rhythms (especially delta and alpha) show a progressive increasing or decreasing trend across physiological aging. To this aim, we analyzed the type of correlation (linear and nonlinear) between cortical EEG rhythms and age. Resting eyes-closed EEG data were recorded in 108 young (Nyoung; age range: 18-50 years, mean age 27.3+/-7.3 SD) and 107 elderly (Nold; age range: 51-85 years, mean age 67.3+/-9.2 SD) subjects. The 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 low-resolution brain electromagnetic tomography (LORETA). Statistical results showed that delta sources in the occipital area had significantly less magnitude in Nold compared to Nyoung subjects. Similarly, alpha 1 and alpha 2 sources in the parietal, occipital, temporal, and limbic areas had significantly less magnitude in Nold compared to Nyoung subjects. These nine EEG sources were given as input for evaluating the type (linear, exponential, logarithmic, and power) of correlation with age. When subjects were considered as a single group there was a significant linear correlation of age with the magnitude of delta sources in the occipital area and of alpha 1 sources in occipital and limbic areas. The same was true for alpha 2 sources in the parietal, occipital, temporal, and limbic areas. In general, the EEG sources showing significant linear correlation with age also supported a nonlinear correlation with age. These results suggest that the occipital delta and posterior cortical alpha rhythms decrease in magnitude during physiological aging with both linear and nonlinear trends. In conclusion, this new methodological approach holds promise for the prediction of dementia in mild cognitive impairment by regional source rather than surface EEG data and by both linear and nonlinear predictors.
246 citations
TL;DR: The present results suggest that at group level, fronto-parietal coupling of the delta and alpha rhythms progressively becomes abnormal though MCI and mild AD.
169 citations
TL;DR: The present findings support the 'transition hypothesis' of brain structural and functional continuity between MCI and AD and confirmed for the first time the hypothesis that the sources of resting delta rhythms are correlated with lobar brain volume.
158 citations
TL;DR: Compared with medical treatment, closure of PFO brings about a significant overall improvement in migraine, which seems to occur irrespective of migraine type and of previous cerebrovascular disease.
Abstract: Background and Purpose— Transcatheter closure of patent foramen ovale (PFO) has been reported to improve migraine in patients with cerebrovascular disorders in noncontrolled studies. The aim of the study was to compare the course of migraine assessed prospectively over a 12-month period in symptomatic (for cerebrovascular disease) and asymptomatic patients undergoing PFO closure and in patients with PFO treated medically. Methods— Twenty-three stroke symptomatic (SS; 39±10 years of age; males/females [M/F] 5/18) and 27 stroke asymptomatic (SA; 40±12 years of age; M/F 5/22) patients with migraine underwent PFO closure. Twenty-seven patients with migraine and PFO (controls [CTRLS]; 36±11 years of age; M/F 4/23) were followed up medically. Migraine severity was assessed at baseline with a scale that takes into account the frequency, duration, and intensity of the attacks and the occurrence of aura (score range 0 to 10). Six months later, the patients were given a structured diary to annotate monthly with the...
136 citations
TL;DR: The regions of the hippocampal formation that are found atrophic in AD patients are those known to be affected from pathological studies, and this study supports the possibility of carrying out in vivo macroscopic neuropathology of the hippocampus with MR imaging in the neurodegenerative dementias.
130 citations
TL;DR: Neuropsychological patterns identify groups of patients with MCI showing specific clinical features and risk of progression to dementia and MTA clinically rated with a visual scale is the most relevant predictor of progression and improvement.
Abstract: Background: The diagnosis of mild cognitive impairment (MCI) is clinically unhelpful, as many patients with MCI develop dementia but many do not. Objective: To identify clinical instruments easily applicable in the clinical routine that might be useful to predict progression to dementia in patients with MCI assessed in the outpatient facility of a memory clinic. Participants and methods: 52 dementia-free patients (mean (standard deviation) age 70 (6) years; 56% women) with MCI, and 65 healthy controls (age 69 (6) years; 54% women) underwent brain magnetic resonance scan with standardised visual assessment of medial temporal atrophy (MTA) and subcortical cerebrovascular lesions (SVLs). Follow-up assessment occurred 15.4 (SD 3.4) months after baseline to detect incident dementia and improvement, defined as normal neuropsychological performance on follow-up. Results: Patients were classified into three groups according to the presence of memory disturbance only (MCI Mem), other neuropsychological deficits (MCI Oth) or both (MCI Mem+). MCI Mem and Mem+ showed MTA more frequently (31% and 47% v 5% and 14% of controls and MCI Oth, p Conclusion: Neuropsychological patterns identify groups of patients with MCI showing specific clinical features and risk of progression to dementia. MTA clinically rated with a visual scale is the most relevant predictor of progression and improvement.
99 citations
TL;DR: The present multicentric EEG study tested the hypothesis that presence of ε4 affects sources of resting EEG rhythms in both MCI and AD subjects.
Abstract: Objective
Relationships between the apolipoprotein E e4 allele and electroencephalographic (EEG) rhythmicity have been demonstrated in Alzheimer's disease (AD) patients but not in the preclinical stage prodromic to it, namely, mild cognitive impairment (MCI). The present multicentric EEG study tested the hypothesis that presence of e4 affects sources of resting EEG rhythms in both MCI and AD subjects.
Methods
We enrolled 89 MCI subjects (34.8% with e4) and 103 AD patients (50.4% with e4). Resting eyes-closed EEG data were recorded for all subjects. EEG rhythms of interest were delta (2—4Hz), theta (4–8Hz), alpha 1 (8–10.5Hz), alpha 2 (10.5–13Hz), beta 1 (13–20Hz), and beta 2 (20–30Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography.
Results
Results showed that amplitude of alpha 1 and 2 sources in occipital, temporal, and limbic areas was lower in subjects carrying the e4 allele than in those not carrying the e4 allele (p < 0.01). This was true for both MCI and AD. For the first time to our knowledge, a relationship was shown between ApoE genotype and global neurophysiological phenotype (ie, cortical alpha rhythmicity) in a preclinical AD condition, MCI, in addition to clinically manifest AD.
Interpretation
Such a demonstration motivates future genotype–EEG phenotype studies for the early prediction of AD conversion in individual MCI subjects. Ann Neurol 2005
94 citations
TL;DR: VBM indicated that estrogen use was associated with greater gray matter volumes in the whole group of treated women, which included the cerebellum and cerebral cortices and, typically involved in Alzheimer's disease, the medial temporal structures and the temporoparietal junction.
Abstract: 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.
TL;DR: The present findings represent the first demonstration of relationships between the AD genetic risk factor CST3 B and global neurophysiological phenotype (i.e., cortical delta and alpha rhythmicity) in MCI and AD subjects, prompting future genotype-EEG phenotype studies for the early prediction of AD conversion in individual MCI subjects.
TL;DR: It is proposed that the trophic effect of estrogens on cerebellum might account for the observed improvement in cognition, and ERT use appears to improve linguistic, attentive and planning abilities.
TL;DR: This study adds a new perspective about the role of COPD, heart failure, peripheral artery diseases, diabetes and not life-threatening cancer on functional recovery, emphasizing their combined impact in elderly people.
TL;DR: It is suggested that frontal WMHs are associated with frontal gray matter damage while parietooccipital WMHS seem to have a weaker and more diffuse impact on gray matter.
Abstract: White matter hyperintensities (WMHs) are a common finding in normal elderly persons. We studied the biological damage associated with WMHs by assessing the correspondence between WMH location and regional gray matter loss.Voxel-based morphometry of the gray matter was carried out with statistical parametric mapping on high resolution MR images.Neurologically intact persons with mainly anterior (frontal>parieto-occipital; N = 39) and mainly posterior WMHs (parieto- occipital>frontal; N = 14) were compared with a group devoid of WMHs (N = 80). Subjects with mainly frontal WMHs had bilateral frontal (medial, superior, and inferior gyri) atrophy in gray matter, while subjects with mainly posterior WMHs had more diffuse atrophy, involving mainly the frontal but also the right insular region. Our findings suggest that frontal WMHs are associated with frontal gray matter damage while parietooccipital WMHs seem to have a weaker and more diffuse impact on gray matter.
TL;DR: A possible effect on synaptic plasticity or neurodevelopment might explain the influence of the His452Tyr polymorphism on temporal brain structures, and this might be the basis for poorer memory performance in 452Tyr carriers.
Abstract: Serotonin (5-HT) receptors 2A are expressed in brain regions involved in memory and learning processes. Recently, a functional single nucleotide polymorphism in the 5-HT2A receptor gene leading to an amino-acid substitution at residue 452 (His452Tyr) has been involved in memory performance, persons with the rare 452Tyr allele showing poorer memory performance compared to His452His subjects. To investigate a putative structural effect of this polymorphism on temporal areas typically involved in memory processes, we performed voxel-based morphometry (VBM) and region-of-interest (ROI) volumetric analysis on high-resolution magnetic resonance images in 15 carriers and 61 noncarriers of the 452Tyr allele. ROI volumetric analysis showed a significant reduction of the fractional volume of the temporal white matter in 452Tyr carriers (0.67+/-0.07 vs 0.73+/-0.08; P=0.007). VBM confirmed this finding and in addition showed reduced grey matter in the left hippocampus, left inferior temporal gyrus, and bilaterally in the middle and superior temporal gyrus. A possible effect on synaptic plasticity or neurodevelopment might explain the influence of the His452Tyr polymorphism on temporal brain structures, and this might be the basis for poorer memory performance in 452Tyr carriers. These findings should be considered preliminary and future replication is needed.
TL;DR: A rehabilitative intervention based on current neuropsychological concepts and on awareness of the mechanisms of pathological ageing of cognition provides the possibility of tailored treatments for many different patients, an important reduction of burn-out in the personnel, and clinically relevant outcomes, such as an implicit orientation for the patient, with beneficial effects on mood and behavior.
TL;DR: The known group validity showed a specificity between 87% and 91% and a sensitivity between 92% and 100% in correctly identifying AD in age classes ranging from 50 to 65 and 66 to 80 years and the test is a valid instrument for the screening of AD.
Abstract: The aim of the present study was to validate a short, ecological test of episodic memory for the screening of Alzheimer's disease (AD). The validation was performed by computing intrarater reliability, homogeneity, internal coherence, convergent, discriminant and known group validities in the performance of normal subjects (N = 65), mild cognitive impairment (MCI) patients (N = 114), and AD (N = 44) and non-AD demented (N = 39) patients. Intrarater reliability was 0.88, homogeneity ranged from 0.81 to 0.97, and internal coherence was 0.87. With respect to convergent and discriminant validities, the test loaded strongly on memory factor (value = 0.64) and weakly on other nonmemory factors. The known group validity showed a specificity between 87% and 91% and a sensitivity between 92% and 100% in correctly identifying AD in age classes ranging from 50 to 65 and 66 to 80 years. The test is a valid instrument for the screening of AD.
TL;DR: Which drugs were prescribed in 2004 for cognitive and non cognitive disturbances of patients with MCI in a sizable group of Italian expert centers for the diagnosis and treatment of Alzheimer's disease are described.
Abstract: Objectives
Today there are no data on the type of drugs prescribed to MCI patients nor the prevalence of their prescription. The aim of this study was to describe which drugs were prescribed in 2004 for cognitive and non cognitive disturbances of patients with MCI in a sizable group of Italian expert centers for the diagnosis and treatment of Alzheimer's disease.
Methods
Eighty-eight of the 314 contacted UVAs (28%) agreed to take part to the present study. The physicians were surveyed with a structured questionnaire assessing questions related to prescription of drug therapy based on their subjective judgement.
Results
Cholinesterase inhibitors are prescribed to 90% of patients with AD but, interestingly, to about one in four patients with MCI (27%). Gingko and nootropics are prescribed infrequently, but in MCI two to three times more often than in AD. About one in four (27%) and one in ten (9%) MCI patient are prescribed SSRIs and benzodiazepines, a proportion similar to that of AD (28% and 10%), while atypical and traditional neuroleptics are virtually never used in MCI patients. Vitamin E is prescribed to more than half of MCI (57%) and in about half as many AD patients (27%).
Conclusions
These data suggest that lacking approved or clearly effective drugs for cognitive symptoms, physicians respond with ‘analogy treatments’ and by increasing the prescription of ‘accessory drugs’. Non cognitive symptoms in MCI are managed virtually exclusively with SSRIs and benzodiazepines. Copyright © 2006 John Wiley & Sons, Ltd.
TL;DR: This review describes some advanced imaging analysis techniques aimed at studying brain structural images and how these techniques might benefit clinical practice through image data sharing and remote analysis in order to increase the accuracy of diagnosis in patients with cognitive impairment.
Abstract: Cognitive impairment, especially in its early stages, is associated with very mild signs and symptoms that are difficult to detect by clinical and neuropsychological assessment. Advanced imaging analysis techniques applied to magnetic resonance images allow the detection of cerebral structural changes in vivo in mildly affected patients, and might be a useful supporting tool in the early diagnosis and treatment of patients with cognitive impairment. The increasing importance of computer science in cognitive neuroscience has led to the dissemination of a new discipline, neuroinformatics, which is crucial for the introduction of research findings into clinical practice. This review describes some advanced imaging analysis techniques aimed at studying brain structural images and how these techniques might benefit clinical practice through image data sharing and remote analysis in order to increase the accuracy of diagnosis in patients with cognitive impairment.
TL;DR: Normal values are nearly identical with each of the published methods of automated EAS MUP quantitation with the exception of some DQEMG increase in duration with age.
TL;DR: In vitro binding and IHC/IF studies suggest that PIB is not a very specific ligand for -synuclein, and C-PIB retention in brains of DLB patients might indicate PIB primarily binding to A plaques and not LBs.
Abstract: M). Inhibition studies were performed with 2 and 10nM H-PIB on 0.5 and 2.0 g/ml -syn, with increasing concentrations (1nM 20 M) of cold PIB. Fixed serial sections (5-7 m) of DLB frontal cortex brain tissue were analyzed by IF and IHC microscopy, utilizing PIB and an -syn antibody, respectively. Results: In vitro binding assays indicated that H-PIB binds to A 42 fibrils in a saturable manner and exhibited affinities in the nanomolar range (KD 10 nM), while the KD for -syn was impossible to establish given the very low total ( 12%) and specific binding to -syn fibrils ( 5%). Inhibition studies with -syn showed very low competition with cold PIB. IF and IHC microscopy indicated that PIB failed to stain/ bind LBs. Conclusions: In vitro binding and IHC/IF studies suggest that PIB is not a very specific ligand for -synuclein. Therefore, C-PIB retention in brains of DLB patients might indicate PIB primarily binding to A plaques and not LBs.
TL;DR: It is argued that particular working conditions entailing frequent Valsalva maneuvers may represent a risk factor for the development of migraine in subjects with right-to-left shunt and the hypothesis that the beneficial effect of atrial septal repair on migraine in stroke patients might result not so much from the correction of the shunt but mainly from changes in lifestyle that reduce the number or the strength of ValsAlva strains.
Abstract: Response:
Magrini and associates argue that particular working conditions entailing frequent Valsalva maneuvers may represent a risk factor for the development of migraine in subjects with right-to-left shunt. This is a clever and intriguing observation that, besides being biologically plausible, raises the hypothesis, never considered so far, that the beneficial effect of atrial septal repair on migraine in stroke patients might result not so much from the correction of the shunt but mainly from changes in lifestyle that reduce the number or the strength of Valsalva strains. This variable will have to be taken into account in future studies.
However, …