Stationary stable cross-correlation pattern and task specific deviations in unresponsive wakefulness syndrome as well as clinically healthy subjects.

Brain dynamics is highly non-stationary, permanently subject to ever-changing external conditions and continuously monitoring and adjusting internal control mechanisms. Finding stationary structures in this system, as has been done recently, is therefore of great importance for understanding fundamental dynamic trade relationships. Here we analyse electroencephalographic recordings (EEG) of 13 subjects with unresponsive wakefulness syndrome (UWS) during rest and while being influenced by different acoustic stimuli. We compare the results with a control group under the same experimental conditions and with clinically healthy subjects during overnight sleep. The main objective of this study is to investigate whether a stationary correlation pattern is also present in the UWS group, and if so, to what extent this structure resembles the one found in healthy subjects. Furthermore, we extract transient dynamical features via specific deviations from the stationary interrelation pattern. We find that (i) the UWS group is more heterogeneous than the two groups of healthy subjects, (ii) also the EEGs of the UWS group contain a stationary cross-correlation pattern, although it is less pronounced and shows less similarity to that found for healthy subjects and (iii) deviations from the stationary pattern are notably larger for the UWS than for the two groups of healthy subjects. The results suggest that the nervous system of subjects with UWS receive external stimuli but show an overreaching reaction to them, which may disturb opportune information processing.

Healthcare-associated infections and antimicrobial resistance in severe acquired brain injury: a retrospective multicenter study.

Background: Recent studies underscore that healthcare-associated infections (HAIs) and multidrug-resistant (MDR) HAIs affect rehabilitation outcomes and hospital length of stay (LOS) for severe acquired brain injury (sABI). Objective: This study aimed to estimate HAI incidence in different sABI rehabilitation settings and determine risk factors and HAI impact on neuromotor and cognitive recovery. Methods: We conducted a retrospective multicenter study in two semi-intensive units (SICUs), two high-specialty post-acute units (PAUs), and one long-term care (LTC) rehabilitation facility. Data extraction was performed by experienced clinicians, using a structured Excel file and they agreed upon criteria for case definitions of healthcare. The main outcome measures were the HAI and MDR HAI incidence and the LOS, the functional recovery was measured using the Level of Cognitive Functioning and Disability Rating Scale. Results: There were 134 sABI participants. The calculation of the probability level was adjusted for three pairwise comparisons among settings (0.05/3 = 0.017). The HAI and MDR HAI incidences were significantly higher in SICU (3.7 and 1.3 per 100 person-days) than in other settings (LTC: 1.9, p = 0.034 and 0.5, p = 0.026; PAU: 1.2, p < 0.001 and 0.3, p < 0.001). HAI and MDR HAI risk variables included older age, an increased number of devices, and carbapenemase-producing Enterobacteriaceae (CPE) colonization, while a high prealbumin plasma value seemed to have a protective effect. Conclusion: HAIs are related to longer LOS, and colonization is associated with poor prognosis and poor functional outcomes with reduced ability to achieve the cognitive capacity of self-care, employability, and independent living. The need to ensure the protection of non-colonized patients, especially those with severe disabilities on admission, is highlighted.

Morfeo Study II: Clinical Course and Complications in Patients With Long-Term Disorders of Consciousness.

BACKGROUND: The life expectancy of patients with disorders of consciousness (DOCs) is ever-increasing, but little is known about their clinical course over late stages. Several issues (premorbid conditions, complications and pressure sores) are to be considered for their effect on clinical outcome, risk of death and recovery of functional performance. Unfortunately, in late stages of long-term rehabilitation, these aspects are still more neglected than in acute and postacute stages. The aim of this study was to investigate the clinical course and the complications of patients in the late stages of DOCs and to explore the relationship between mortality and specific biomarkers. MATERIALS AND METHODS: A total of 112 patients, admitted over 10 years in a dedicated ward, were retrospectively studied. Sociodemographic data, preadmission and inpatient clinical features were collected. Disability Rating Scale scores, complications including pressure sores and blood markers were assessed monthly. Data were analyzed through descriptive statistics and correlations using SPSS. RESULTS: Most patients were men older than 50 years with a nontraumatic etiology and a history of hypertension (42.86%). The most common complication was pneumonia (76.79%). No association was found between sex and mortality or between etiology and mortality (P > 0.05). Mortality correlated significantly with sepsis (ρ = 0.253), albumin (ρ = -0.558), hemoglobin (ρ = -0.354) and white blood cells (ρ = 0.243). Only 42% of patients remained unchanged at Disability Rating Scale evaluation. CONCLUSIONS: These data confirmed that DOCs are not static conditions and they require ongoing monitoring and assessment of clinical status, level of consciousness and laboratory biomarkers.

Anxious attachment style and hopelessness as predictors of burden in caregivers of patients with disorders of consciousness: a pilot study.

OBJECTIVE: Previous studies on caregivers of patients with disorders of consciousness (DOCs) have highlighted that their overall burden is not related to disease duration or diagnosis, but mainly to their personal characteristics. The aim of this study was to investigate the impact of attachment style and hopelessness on overall burden in caregivers of patients in both vegetative state and minimally conscious state. METHODS AND PROCEDURE: Nineteen caregivers of patients with DOCs, hosted in a long-term care facility, were assessed using the Caregiver Burden Inventory, the Attachment Style Questionnaire, and the Beck Hopelessness Scale. Socio-demographic information was also collected. Data were analysed through descriptive statistics, correlations, one sample t-test and a multiple regression analysis using SPSS. OUTCOMES AND RESULTS: Burden was not associated with duration of caregiving and gender had no effect on overall burden. Multiple regression analysis indicated that preoccupied attachment style and hopelessness together predicted 49% of the total variability of burden (R(2 )= 0.489; adjusted R = 0.43). CONCLUSIONS: These data suggest that caregivers need psychological assessment and support in order to keep under control the level of burden and to help themselves be a better resource for their relatives.

Does age at observation time affect the clinical presentation of mild cognitive impairment?

BACKGROUND: To date, there are no published data investigating the role of age in the clinical and neuropsychological presentation of mild cognitive impairment (MCI). The aim of the study was to evaluate whether age at the time of evaluation modulates clinical, functional or cognitive profiles in MCI subjects. METHODS: A total of 167 outpatients with a clinical diagnosis of MCI were consecutively enrolled and entered in the study. Clinical and demographic characteristics were carefully recorded. Each patient underwent a wide neuropsychological standardized assessment. RESULTS: MCI subjects were divided into 3 groups according to their age at observation time: 58 MCI patients were classified as young (≤ 69 years), 89 as old (70-79 years) and 20 as very old (≥ 80 years). The 3 groups did not differ in demographic characteristics, general cognitive functions and memory impairment. Very old MCI subjects showed a significantly greater impairment than younger MCI patients in cognitive domains involving executive functions. In particular, very old MCI patients were more frequently classified as having multiple-domain amnestic MCI. CONCLUSION: Present data highlight that the clinical presentation of MCI is affected by age: at presentation, very old MCI subjects show a worse performance than younger MCI subjects on multiple abilities, particularly on executive functions.

Efficacy of SSRIs on cognition of Alzheimer's disease patients treated with cholinesterase inhibitors.

BACKGROUND: This study examines the joint effect on cognition of selective serotonin re-uptake inhibitors (SSRIs) and cholinesterase inhibitors (AChEIs) in depressed patients affected by Alzheimer's disease (AD) living at home. METHODS: The study was conducted in two different outpatient neurological clinics. 338 patients with probable AD were treated with ChEis (donepezil, rivastigmine and galantamine) as per the clinician's judgment and were observed for nine months. At study entry, participants underwent a multidimensional assessment evaluating cognitive, functional and psychobehavioral domains. All patients were evaluated at baseline, after one (T1), three (T2) and nine months (T3). Patients were grouped in three different categories (patients not depressed and not treated with SSRIs, patients depressed and treated with SSRIs, and patients depressed but not treated with SSRIs). RESULTS: At baseline 182 were diagnosed as not depressed and not treated with SSRIs, 66 as depressed and treated with SSRIs, and 90 as depressed but not treated with SSRIs. The mean change in MMSE score from baseline to nine months showed that depressed patients not treated worsened in comparison with those not depressed and not treated with SSRIs (mean change -0.8 +/- 2.3 vs 0.04 +/- 2.9; p = 0.02) and patients depressed and treated with SSRI (mean change -0.8 +/- 2.3 vs 0.1 +/- 2.5; p = 0.03). CONCLUSIONS: In AD patients treated with AChEIs, SSRIs may exert some degree of protection against the negative effects of depression on cognition.

The importance of Alzheimer disease assessment scale-cognitive part in predicting progress for amnestic mild cognitive impairment to Alzheimer disease.

The aim of this study was to verify the usefulness of Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog), in screening participants at risk of developing Alzheimer disease (AD) among populations with amnestic mild cognitive impairment(aMCI). 98 outpatients with aMCI were recruited. Participants were revaluated after 1 year: 44 (44.9%) were progressed to AD (progressors), while 54 (55.1%) did not convert (nonprogressors MCI). At baseline, cognitive performances were more impaired in progressors assessed by MMSE and by a neuropsychological battery. When tested with the ADAS-Cog subscale, the 2 groups of participants at baseline, progressors, and nonprogressors MCI, were significantly different regarding total score, memory, and nonmemory subitems. Considering a cutoff of 9.5 total score, adjusted for education, ADAS-Cog subscale showed a good performance (area under the curve = 0.67; sensitivity = 0.62%; specificity = 0.73%) in predicting conversion from aMCI to AD. Progressors aMCI were characterized at baseline by a greater cognitive impairment. ADAS-Cog subscale is a useful and brief cognitive assessment tool to screen aMCI participants converting to AD within 1 year.

Mild parkinsonian signs and psycho-behavioral symptoms in subjects with mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) may be accompanied by extra pyramidal signs (EPS), which are related to the severity and type of cognitive impairment. We aimed to elucidate further the relationship between MCI and EPS, analyzing the correlation between the severity of EPS and cognitive functions, and the presence of EPS and neuro-psychiatric features. METHODS: Data were obtained from a longitudinal study of 150 MCI outpatients. Participants underwent a clinical assessment including the Unified Parkinson Disease Rating Scale, the Neuropsychiatric Inventory, the Tinetti Scale, and a standardized neuropsychological battery. Mild EPS could be defined as being present (MCI with mild EPS) using a subscale of UPDRS, based on three specific symptoms: bradykinesia, rigidity and tremor. RESULTS: The two groups, one with mild EPS (24%) and one without EPS (76%), differed in gait abnormalities and presence of extrapyramidal symptoms. Groups did not differ in terms of general cognitive functions evaluated using the Mini-mental State Examination, while subjects with MCI with mild EPS performed significantly worse than those with MCI without EPS in total global score and in non-memory items of the Alzheimer's Disease Assessment Scale. Moreover, severity of EPS was significantly correlated with low performance on executive functions and with high performance on episodic memory. The group with MCI with mild EPS were observed to have a greater prevalence of patients with anxiety, depression, apathy and sleep disturbances than in MCI without EPS. CONCLUSION: MCI may be associated with mild parkinsonian signs, the severity of which are related to the severity of cognitive impairment, in particular of non-memory functions, and to a differential pattern of psycho-behavioral symptoms.

Serum albumin level interferes with the effect of donepezil in Alzheimer's disease.

BACKGROUND AND AIMS: The most successful therapeutic approaches to Alzheimer's disease (AD) have involved acetylcholinesterase inhibitors (ChEIs). In view of the different response rates to ChEIs therapy, it is important to identify the pharmacokinetic and pharmacodynamic mechanisms which may interfere with this effect. The aim of the study is to evaluate the efficacy on cognition of donepezil, a cholinesterase inhibitor, in a sample of mild to moderate AD patients with various serum albumin levels, a condition modifying drug distribution. METHODS: Ninety-eight Alzheimer patients treated with donepezil were analyzed in an outpatient clinic between January 2003 and January 2005. At study entry, participants underwent multidimensional assessment evaluating cognitive, functional and psychobehavioral domains. All concomitant illnesses and treatments were recorded. Patients were grouped in three categories (with low, medium and high albumin levels). RESULTS: The total sample of patients showed cognitive improvement from baseline of the ADAS Cog score at three months (ADAS Cog mean change -1.4+5.4; p=0.01), cognitive stabilization at nine (ADAS Cog mean change 0.03+6.7; p=ns), and not statistically significant worsening at fifteen months (ADAS Cog mean change 0.9+7.3; p=ns). The low serum albumin level group was associated with a greater response to donepezil. In fact, cognition, evaluated by the ADAS Cog mean change from baseline, improved during the first 15 months of treatment in the low serum albumin level group, but worsened in the two higher groups. CONCLUSION: Our preliminary data suggest that serum albumin level should be monitored to evaluate the clinical efficacy of ChEIs therapy.

Acetylcholinesterase inhibitors and depressive symptoms in patients with mild to moderate Alzheimer's disease.

BACKGROUND AND AIMS: Acetylcholinesterase inhibitor (AChEis) therapy in Alzheimer Disease (AD) has been shown to provide cognitive benefits and to slow progression of the disease. AChEis have also been demonstrated to improve behavioral symptoms, although there seem to be subtle differences in the magnitude of response. The aim of our study was to evaluate the effect of 16 weeks treatment with AChEis on depressive symptoms in a selected sample of AD patients in routine clinical practice. SUBJECTS AND METHODS: A study of 135 patients with Alzheimer's disease. All subjects were assessed at baseline (upon initiation of AChEis therapy) and re-evaluated after 16 weeks. RESULTS: At baseline, "Depressed" and "Not depressed" patients were categorized according to DSM IV criteria for depression in Alzheimer Disease. After 16 weeks of treatment with AchEis, we observed an improvement of mood in the "Depressed" patients. In this group "Mood symptoms", measured with GDS, were independently associated with GDS "Mood symptoms" at baseline, but not with improvement on cognition (mean change of MMSE), age or sex. CONCLUSIONS: In depressed AD subjects, AChEis treatment improves depressive symptoms evaluated by GDS. This improvement is independent of cognition enhancement.

Conversion of amnestic Mild Cognitive Impairment to dementia of Alzheimer type is independent to memory deterioration.

BACKGROUND: Mild Cognitive Impairment defines a transitional stage between normal ageing and dementia, and reflects the clinical situation where a person has memory complaints and objective evidence of cognitive impairment but no evidence of dementia. To plan the care of patients with MCI, it is important to predict as accurately as possible potential risk factors modulating the conversion to AD. AIM: To investigate the risk factors associated of conversion to dementia of Alzheimer type (AD) for subjects with amnestic Mild Cognitive Impairment (aMCI). METHODS AND MATERIALS: One hundred nineteen subjects consecutively recruited who met the operational criteria for aMCI (with or without deficits in other cognitive domains). They underwent multidimensional assessment and a neuropsychological battery at baseline and at follow-up, after 1 year. Diagnosis for dementia was based on a deficit in two or more cognitive domains severe enough to affect the participant functional abilities. Subjects converted to AD over time were classified as Demented; subjects that remained unchanged, or became cognitively normal during follow-up, were defined as Stable. RESULTS: Demented MCI (N = 40; 33.6%) were older (mean age 73.5 +/- 8.5 vs. 69.2 +/- 7.0; p = 0.006) when compared to Stable (N = 79; 66.4) and their global cognitive performances, at baseline, were more compromised when assessed by ADAS-Cog (mean score 10.7 +/- 3.9 vs 6.7 +/- 3.4; p = .000) and by MMSE (mean score 26.1 +/- 1.9 vs. 27.3 +/- 1.8; p = 0.002). Demented were similarly compromised in basic activities of daily living (BADL mean 0.2 +/- 0.4 vs 0.1 +/- 0.3 functions lost; p = NS) but more compromised on instrumental daily functions (IADL mean 0.7 +/- 0.8 vs. 0.1 +/- 0.5 functions lost; p = 0.001). The presence of white matter lesions (WML) on CT or MRI was more pronounced in Demented group (p = 0.02). After 1 year; Demented worsened on phonemic verbal fluency (PFL) (p = 0.009), Raven's coloured matrices (p = 0.003), Trail Making test A and B (p = 0.008 and p = 0.007 respectively) and in Instrumental Activities of Daily Living (IADL) (p =0 .000) respect to Stable. Logistic regression analysis revealed that ADAS-Cog basal score, Trail Making B, IADL but not memory deterioration were significantly associated to the conversion to AD. CONCLUSIONS: In subjects with aMCI poor global cognitive performance at baseline, the worsening on executive functions and on functional status but not the worsening on memory functions are independently associated with the conversion to dementia of Alzheimer type at 1 year, follow-up.

Cognitive and psychopathologic response to rivastigmine in dementia with Lewy bodies compared to Alzheimer's disease: a case control study.

Cholinesterase inhibitors (ChEIs) are effective in improving cognition and behavior in patients affected by Alzheimer's disease (AD) as well as by Lewy bodies dementia (DLB). The authors compared the effect of rivastigmine in the treatment of cognitive impairment and behavioral and psychological symptoms of dementia (BPSD) in 30 AD and in 30 DLB patients. At baseline, DLB compared to AD patients showed a greater number of extrapyramidal symptoms (P < .005) and were similar regarding cognitive symptoms and BPSD. After treatment, both groups showed a comparable cognitive and psycho-behavioral improvement. A significant difference between AD and DLB patients was found for hallucinations (P < .002). Rivastigmine produces comparable cognitive benefits in patients with DLB and AD and also a significant improvement of behavioral disorders. These findings support the view that ChEIs should be considered a first-line treatment of the cognitive and psycho-behavioral symptoms of both AD and DLB.

Angiotensin converting enzyme (ACE) inhibitors modulate the rate of progression of amnestic mild cognitive impairment.

BACKGROUND: Predictors of progression to dementia in individuals with mild cognitive impairment (MCI) define different groups with higher risks of progression. To date, efforts to differentiate those who will progress to dementia from those who will not have proved inconclusive, and while grades of risk have been identified, their generalizability is not clear. AIM: To examine the clinical and socio-demographical risk factors for progression of memory decline in a sample of subjects with referred memory complaints who met criteria for amnestic MCI. METHODS AND MATERIALS: Seventy-four subjects consecutively recruited who met the operational criteria for amnestic MCI. They underwent multidimensional assessment and a neuropsychological battery at baseline and at follow-up, after one year. Memory decline was defined using the short story mean score change (at follow-up and at baseline). Subjects showing memory decline, with or without conversion to AD over time, were classified as having progressive MCI; subjects that remained unchanged or improved during follow-up were considered as having stable MCI. RESULTS: Subjects with progressive MCI (n = 39, 53%) were older (p = <0.001) and more educated (p = 0.01) compared to stable MCI (n = 35, 47%) and their global cognitive performances, at baseline, were more compromised when assessed by ADAS-Cog (p = 0.05). Antihypertensive drug prescription was greater in the stable MCI compared to progressive MCI (p = 0.01) and significant higher levels of plasma total homocysteine were observed in progressive MCI (p = 0.03). When analyzed in a logistic regression model, the prescription of Angiotensin Converting Enzyme Inhibitors (ACE) was found to be independently associated to the stability of cognitive function, whereas older age, higher education, higher levels of plasma total homocysteine and total ADAS-Cog basal score were independently associated with the progression of cognitive decline. CONCLUSIONS: Older age, higher education, poor global cognitive performance, higher levels of plasma total homocysteine are independently associated with the progression of memory decline while the prescription of ACE Inhibitors is a protective factor for cognitive deterioration.

Effects of cholinesterase inhibitors appear greater in patients on established antihypertensive therapy.

INTRODUCTION: There is increasing evidence that hypertension may contribute to development of dementia. Studies show that blood pressure lowering therapy might protect against cognitive deterioration and that antihypertensive treatment reduce the incidence of dementia. AIM: We hypothesize that administration of cholinesterase inhibitors (AChEis) to patients with Alzheimer's Disease (AD) receiving antihypertensive medications therapy would result in clinical benefits for a period of 40 weeks in routine clinical practice. METHODS AND MATERIALS: Patients with possible or probable AD were enrolled from 16 Alzheimer evaluation units (UVA) of Brescia and Cremona (Northern Italy). Patients treated with donepezil, rivastigmine and galantamine for 40 weeks independently of dosages were selected. Patients were evaluated at baseline (T0), 4 weeks (T1), 16 weeks (T2) and 40 weeks (T3). RESULTS: 416 patients completed the study at 40 weeks; of these 255 were 'non users' while 161 utilized antihypertensive drugs ('users'). The mean change in MMSE score from baseline to week 40 demonstrate that antihypertensive-treated patients improved by 0.7 points while patients receiving only AChEis remain stables. Analyzing separately patients (n = 183) that ameliorate (responders) on cognition at T3 ( >/= 1 point MMSE score increase) a significant differences in favor of 'users' antihypertensive drugs over 'non users' on cognition at weeks 16 and 40 has been demonstrated. In particular, at T2 the mean change of MMSE from baseline in 'users' was 3.2 +/- 2.6 vs 'non users' 2.2 +/- 2.3 ( p = 0.016) and at T3 was 3.5 +/- 2.5 vs 'non users' 2.0.2.7+/-1.6 ( p = 0.018). Antihypertensive drugs were independently associated with cognitive improvement in responder patients treated with AChEis (95% CI: 0.41-1.79; p = 0.002). CONCLUSION: Antihypertensive medications in AD patients treated with AChEis are associated with an independent improvement on cognition after 40 weeks of treatment.