Simona Luzzi

Modularity of music: evidence from a case of pure amusia

A case of pure amusia in a 20 year old left handed non-professional musician is reported. The patient showed an impairment of music abilities in the presence of normal processing of speech and environmental sounds. Furthermore, whereas recognition and production of melodic sequences were grossly disturbed, both the recognition and production of rhythm patterns were preserved. This selective breakdown pattern was produced by a focal lesion in the left superior temporal gyrus. This case thus suggests that not only linguistic and musical skills, but also melodic and rhythmic processing are independent of each other. This functional dissociation in the musical domain supports the hypothesis that music components have a modular organisation. Furthermore, there is the suggestion that amusia may be produced by a lesion located strictly in one hemisphere and that the superior temporal gyrus plays a crucial part in melodic processing.

The Role of Carotid Atherosclerosis in Alzheimer's Disease Progression

The aim of this 12-month prospective study was to establish whether severe internal carotid artery stenosis is associated with faster progression of the cognitive impairment in patients with Alzheimers disease (AD). Four hundred and eleven patients with AD underwent extracranial carotid Doppler ultrasound evaluation. Cerebrovascular reactivity to hypercapnia was measured by means of the breath-holding index (BHI) in those with severe carotid artery stenosis using transcranial Doppler ultrasonography. Cognitive status was quantified with the Mini Mental State Evaluation (MMSE). Ninety-eight patients had severe carotid artery stenosis, 41 right (group 1), and 57 left (group 2), while 313 had no significant stenosis (group 3). Group 1 and 2 patients showed an increased probability compared with group 3 patients to develop severe dementia (MMSE scores < 21) during the 12-month follow-up period: OR 2.36 (95% CI: 1.14-4.87) and OR 4.90 (95% CI: 2.65-9.04), respectively (p < 0.05, multiple logistic regression analysis). A BHI value ipsilateral to the stenosis < 0.69 predicted a worse MMSE score at 12 months irrespective of the side of the stenosis. These findings suggest that severe internal carotid artery stenosis can be considered as a marker of a faster rate of progression of the cognitive decline in AD. They also indicate that cerebral hemodynamic evaluation could be applied to identify patients at higher risk of rapid cognitive decline, who may benefit from aggressive treatment, and warrant investigation of the advantages of carotid revascularization procedures in these patients.

Short-term memory binding is impaired in AD but not in non-AD dementias.

Binding is a cognitive function responsible for integrating features within complex stimuli (e.g., shape-colour conjunctions) or events within complex memories (e.g., face-name associations). This function operates both in short-term memory (STM) and in long-term memory (LTM) and is severely affected by Alzheimers disease (AD). However, forming conjunctions in STM is the only binding function which is not affected by healthy ageing or chronic depression. Whether this specificity holds true across other non-AD dementias is as yet unknown. The present study investigated STM conjunctive binding in a sample of AD patients and patients with other non-AD dementias using a task which has proved sensitive to the effects of AD. The STM task assesses the free recall of objects, colours, and the bindings of objects and colours. Patients with AD, frontotemporal dementia, vascular dementia, lewy body dementia and dementia associated with Parkinsons disease showed memory, visuo-spatial, executive and attentional deficits on standard neuropsychological assessment. However, only AD patients showed STM binding deficits. This deficit was observed even when memory for single features was at a similar level across patient groups. Regression and discriminant analyses confirmed that the STM binding task accounted for the largest proportion of variance between AD and non-AD groups and held the greatest classification power to identify patients with AD. STM conjunctive binding places little demands on executive functions and appears to be subserved by components of the memory network which are targeted by AD, but not by non-AD dementias.

Modifications of platelet from Alzheimer disease patients: a possible relation between membrane properties and NO metabolites.

Alzheimer disease (AD) is a chronic neurodegenerative disorder characterised by a progressive loss of memory and cognitive functions. The formation of nitric oxide (NO), by astrocytes, has been suggested to contribute to the neurodegnerative process. Some studies have described the participation of different isoforms of NOS in the progression of AD. The present work was conducted in order to investigate the role played by NO and peroxynitrite in platelets from AD patients, the possible correlation with Na(+)/K(+)-ATPase activity and the intracellular Ca(2+) in the same group of patients as well as the expression of NOS isoenzymes and nitrotyrosine as markers of NO synthesis and reactive protein nitration. NO production was significantly elevated in the platelets from AD patients compared to controls as well as l-arginine/NO-dependent ONOO(-). Membrane Na(+)/K(+)-ATPase activity was significantly decreased in patients than in controls while intracellular Ca(2+) concentration shows an opposite trend. Platelet from AD patients showed a significantly increased 1-[4-(trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence anisotropy compared with controls. Western blot analysis using anti-iNOS and eNOS monoclonal antibodies demonstrated that both isoforms were detectable in cell lysates as well as nitrotyrosine more pronounced in the cell lysates from AD patients than controls. In conclusion, the increased expression and activity of nitrergic system may produce platelet membrane alteration or vice versa. These modifications may contribute further to the neurodegenerative process in AD because the abnormal function of Alzheimer platelets play a very important role in the pathogenesis of the disease.

Vascular predictors of cognitive decline in patients with mild cognitive impairment.

Our aim in this study was to assess the relationship between the state of cerebral vessels and the risk of conversion from mild cognitive impairment (MCI) to Alzheimers disease (AD). We included 117 MCI patients. They underwent an ultrasonographic assessment of common carotid arteries intima-media thickness (IMT) and carotid plaque index. Cerebrovascular reactivity to hypercapnia in the middle cerebral arteries was calculated with the Breath-Holding Index (BHI). After a 12-month follow-up period, neuropsychological examinations demonstrated a progression to dementia in 21 patients. Pathological values of BHI and IMT significantly increased the risk of conversion (BHI: odds ratio, 5.80; 95% confidence interval, 1.83-18.37, p < 0.05; IMT: odds ratio, 3.08; 95% confidence interval, 1.02-9.33; p < 0.05, multinomial logistic regression analysis). Comparison between patients with all normal values and those with the simultaneous alteration of the 2 vascular indexes showed an increase in the risk of conversion from 9% to 33% (ordinal regression analysis). Our findings show that alterations of cerebral vessel functional and anatomic status increase the risk of conversion from MCI to dementia.

Severe carotid stenosis and impaired cerebral hemodynamics can influence cognitive deterioration

Objective: To evaluate whether severe carotid stenosis and related hemodynamics impairment may increase the risk of cognitive deterioration in asymptomatic subjects. Methods: A total of 210 subjects with unilateral asymptomatic severe carotid stenosis and 109 healthy controls were included and prospectively evaluated for a 36-month period. At entry, demographics, vascular risk profile, and pharmacologic treatments were defined. Cerebral hemodynamics was assessed by transcranial Doppler–based breath-holding index (BHI) test. Cognitive status was evaluated with the Mini-Mental State Examination (MMSE) at entry and at the end of the follow-up period. Cognitive deterioration was defined as a decrease in the MMSE score of 3 points or more during the overall follow-up period. Results: Subjects with carotid stenosis showed an increased probability of developing cognitive deterioration compared with the group without stenosis (odds ratio [OR] 4.16 [95% confidence interval (CI) 1.89–9.11]; p < 0.001). The presence of an impaired BHI ipsilateral to the stenosis was associated with an increased incidence of reduction in cognitive performance (OR 14.66 [95% CI 7.51–28.59]; p < 0.001). Conclusions: Our findings show that the presence of a severe carotid stenosis influences cognitive deterioration over a 36-month period in asymptomatic subjects. An associated hemodynamic impairment significantly increases the risk. Evaluation of functional consequences of carotid stenosis may offer the opportunity to select a group with an increased risk of developing cognitive impairment from subjects with asymptomatic severe carotid stenosis.

Motivational Symptoms of Depression Mask Preclinical Alzheimer’s Disease in Elderly Subjects

Background: Althoughthe relationship between depressive disorders and Alzheimer’s disease (AD) is debated, there is evidence that depression may be an early symptom of dementia. Objective: To evaluate depression features prospectively in elderly subjects with a view to identifying a subgroup affected by preclinical AD. Methods: We performed a cohort study on cognitive performances with a 12-month follow-up in out-patients referred to the local Neuropsychology Clinic complaining of memory problems. Two hundred and twenty-two consecutive non-demented subjects were studied using a neuropsychological battery and the Beck Depression Inventory (BDI) and assessed again 1 year later for the possible onset of cognitive impairment. Multivariate analysis was performed to detect independent predictors of dementia development among age, education, neuropsychological test scores and BDI scores and subscores. BDI subscores were obtained by dividing items into three domains corresponding to mood-related, somatic and motivation-related symptoms. Results: At the time of the first evaluation, 124 of the 222 subjects were depressed according to DSM-III-R criteria. At 1 year, 31 of the 124 depressed subjects and 2 non-depressed ones had AD according to NINCDS-ADRDA criteria. Stepwise logistic regression analysis indicated that the subjects who went on to develop dementia had significantly higher total BDI scores and motivational BDI subscores. Among depressed subjects, the probability of being diagnosed with dementia during follow-up was significantly associated with a motivational BDI subscore ≧7 (odds ratio: 3,885, 95% Cl 154–97,902). Comment: Close neuropsychological follow-up of depressed elderly subjects complaining of memory failure and showing apathy is recommended to detect the early stage of AD.

Foreign accent syndrome as the initial sign of primary progressive aphasia

Foreign accent syndrome (FAS) is a rare speech disorder characterised by the emergence of a new accent, perceived by listeners as foreign. FAS has usually been described following focal brain insults, such as stroke. We describe the unusual case of a woman presenting with FAS as the earliest symptom of progressive degenerative brain disease. At presentation, she showed no language or other cognitive impairment, and functional and structural brain imaging were normal. Follow-up 1 year later revealed the emergence of mild expressive language problems. Repeat functional neuroimaging showed mild hypoperfusion of the perisylvian speech area of the left hemisphere, and structural imaging showed mild left perisylvian atrophy. We interpret the case as an unusual presentation of primary progressive non-fluent aphasia. The case provides further evidence of the variable and circumscribed nature of the clinical presentation of focal cerebral degeneration.

Blood pressure variability and stroke outcome in patients with internal carotid artery occlusion

PURPOSE The aim of this study was to evaluate the relationship between arterial blood pressure (BP) variability during the acute phase and the 3-month outcome in ischemic stroke patients with internal carotid artery (ICA) occlusion. METHODS At least 10 BP measurements during the first 48 h after stroke onset were obtained in 89 patients with ICA occlusion. BP profile was described using various parameters: average of recordings, maximum (max), minimum (min), difference between max and min (max-min), standard deviation (SD) and coefficient of variation (CV) for both systolic and diastolic BP. Outcome at 3 months was defined using the modified Rankin Scale (mRS) score corrected for baseline stroke severity. RESULTS Fifty-five patients had a good and 34 a poor outcome. Max values, max-min, SD and CV of both systolic and diastolic BP resulted significantly higher in patients with poor outcome compared to those with good outcome (p<0.05, multivariate adjusted model). CONCLUSIONS In a cohort of acute ischemic stroke patients with ipsilateral ICA occlusion BP variability, assessed in the acute phase, was associated with poor clinical outcome. These preliminary exploratory findings are worthy of further study to be conducted to confirm or confute the role of BP variability in predicting stroke outcome. In order to obtain more comprehensive information, it would also be appropriate to consider the possibility of acquiring data related to the pathophysiology of stroke and to cerebral hemodynamic changes.

Blood pressure variability predicts cognitive decline in Alzheimer's disease patients

The aim of our study was to evaluate whether blood pressure variability influences the rate of cognitive decline in Alzheimers disease (AD). Two hundred and forty AD patients were periodically evaluated for a 12-month period. The blood pressure (BP) status of each patient was defined through mean and coefficient of variation for both systolic and diastolic BP. Progression of cognitive decline was investigated using the Mini Mental State Examination administered at entry and at the end of follow-up. Among the considered BP indices, only systolic BP variability explained the decrease in the Mini Mental State Examination score after adjustment for confounding variables (multiple linear regression: R(2) = 0.603, adjusted R(2) = 0.513; p < 0.001; logistic regression model: odds ratio = 2.882, 95% confidence interval = 1.772-4.495; p < 0.001). The receiver operating characteristic analysis for evaluating the ability of systolic BP variability to predict a faster cognitive decline presented an area under the curve of 0.913 (95% confidence interval = 0.874-0.953; p < 0.001). Our results suggest that BP variability may be added to the list of the potential vascular risk factors and included in the evaluation of AD patients to better define their risk profile.