A comparison of self and proxy quality of life ratings for people with dementia and their carers: a European prospective cohort study.

Objectives: To identify correlates of self-rated and proxy-rated quality of life (QoL) in people with dementia on (i) a dementia-specific and (ii) a capability-wellbeing QoL measure at baseline and 12-month follow-up, and to consider such factors in the context of QoL intervention development.Method: Prospective clinical and demographic data were collected from 451 community-dwelling dyads (mild-moderate dementia) across eight European countries. QoL was measured using the QOL-AD and the ICECAP-O. Multivariate modelling identified correlates of self- and proxy-rated QoL at baseline and at 12-month follow-up.Results: Carer's proxy-ratings of QoL were significantly lower than self-ratings at all time-points for both measures. Proxy-ratings declined over time, but self-ratings remained stable. Baseline predictors of greater self-rated QoL were education, and greater functional ability and relationship quality. Greater proxy-rated QoL was associated with education and greater functional ability, relationship quality, carer social support and carer QoL, lower carer anxiety/depression and less severe neuropsychiatric symptoms in people with dementia. At follow-up, greater self-rated QoL was predicted by greater functional ability, relationship quality, carer social support and having a spousal carer. Greater proxy-rated QoL at follow-up was associated with the same factors as at baseline; however, the dyad living together was an additional predictive factor.Conclusion: Both proxy-ratings and self-ratings of QoL should be interpreted with caution and in the context of each individual caregiving relationship. Different functional, psychosocial, relational and contextual factors influence self- and proxy-ratings, and both sets of factors should be considered in the context of QoL intervention development for the dyad.

Access to community care for people with dementia and their informal carers : Case vignettes for a European comparison of structures and common pathways to formal care.

BACKGROUND: People with dementia and their informal carers often do not receive appropriate professional support or it is not received at the right time. OBJECTIVES: Description and comparison of common pathways to formal community dementia care in eight European countries as a part of the transnational Actifcare project. MATERIALS AND METHODS: The German team was responsible for creating an individual case scenario as a starting point. The research teams in Ireland, Italy, the Netherlands, Norway, Portugal, Sweden, and the United Kingdom were then asked to describe a common pathway to formal dementia care by writing their own vignette using the provided individual case scenario. RESULTS: A transnational qualitative content analysis was used to identify the following categories as being the most important: involved professionals, dementia-specific and team-based approaches, proactive roles, and financial aspects. General practitioners (GPs) are described as being the most important profession supporting the access to formal care in all the involved countries. In some countries other professionals take over responsibility for the access procedure. Dementia-specific approaches are rarely part of standard care; team-based approaches have differing significances in each of the countries. Informal carers are mainly proactive in seeking formal care. The Nordic countries demonstrate how financial support enhances access to the professional system. CONCLUSION: Enhanced cooperation between GPs and other professions might optimize access to formal dementia care. Team-based approaches focusing on dementia care should be developed further. Informal carers should be supported and relieved in their role. Financial barriers remain which should be further investigated and reduced.

Non-ergot dopamine agonist rotigotine as a promising therapeutic tool in atypical parkinsonism syndromes: a 24 months pilot observational open-label study.

Rotigotine (RTG) is a non-ergot dopamine agonist developed as a new transdermal formulation, indicated for use in early and advanced Parkinson's disease (PD). The potential advantages of the RTG patch include immediacy of effect onset, constant drug delivery, better tolerability avoiding drug peaks and easy of use, helping patient's compliance. So, RTG patch appears to be a suitable candidate in the treatment of patients with atypical parkinsonism. The present is an observational study to evaluate the efficacy and tolerability of RTG in patients affected by atypical parkinsonian disorders. 61 subjects with diagnosis of atypical parkinsonian disorders were treated with transdermal RTG. Diagnosis was: Parkinson disease with dementia, multiple system atrophy parkinsonian type, multiple system atrophy cerebellar type, progressive sopranuclear palsy, cortico-basal degeneration, Lewy body dementia and fronto-temporal dementia with parkinsonism. Patients were evaluated by UPDRS-III, NPI, MMSE and adverse events (AEs) were recorded. Patients treated with RTG show an overall decrease of UPDRS III scores without increasing behavioral disturbances. Main adverse events (AE) were hypotension (14 patients), nausea (13), vomiting (5), drowsiness (5), tachycardia (2) dystonia (3 patients, all treated with concomitant l-dopa). On the whole, 16 patients were affected by AE and 7 patients suspended RTG treatment due to AE (vomiting, tachycardia and sleepiness). In our population transdermal RTG seems to be effective and well tolerated. Due to its system of drug delivery, RTG appears to be a suitable therapy in elderly patients as it has a good tolerability profile, improves patient's compliance and helps management of fragile patients.

Electroencephalographic upper/low alpha frequency power ratio relates to cortex thinning in mild cognitive impairment.

OBJECTIVE: Temporoparietal cortex thinning is associated with mild cognitive impairment (MCI) due to Alzheimer disease (AD). The increase in EEG upper/low α frequency power ratio has been associated with AD converter MCI subjects. We investigated the association of the EEG upper/low α frequency power ratio with patterns of cortical thickness in MCI. METHODS: 74 adult subjects with MCI underwent clinical and neuropsychological evaluation, electroencephalography (EEG) recording and high-resolution 3-dimensional magnetic resonance imaging (MRI). The EEG upper/low α frequency power ratio as well as cortical thickness were computed for each subject. Three MCI groups were detected according to increasing tertile values of EEG upper/low α frequency power ratios, and the difference of cortical thickness among the groups was estimated. RESULTS: The EEG high upper/low α frequency power ratio group had a total cortical grey matter volume reduction of 471 mm(2), greater than that of the EEG low upper/low α frequency power ratio group (p < 0.001). The EEG high upper/low α frequency power ratio group showed a similar but less marked pattern (160 mm(2)) of cortical thinning when compared to the EEG middle upper/low α frequency power ratio group (p < 0.001). Moreover, the EEG high upper/low α frequency power ratio group had wider cortical thinning than other groups, mapped to the supramarginal gyrus and precuneus bilaterally. No significant regional cortical thickness differences were found between middle and low EEG upper/low α frequency power ratio groups. CONCLUSION: A high EEG upper/low α frequency power ratio was associated with temporoparietal cortical thinning in MCI subjects. The combination of upper/low α frequency power ratio and cortical thickness measurement could be useful for identifying individuals at risk for progression to AD dementia and may be of value in the clinical context.

Quantitative EEG Markers in Mild Cognitive Impairment: Degenerative versus Vascular Brain Impairment.

We evaluated the relationship between brain rhythmicity and both the cerebrovascular damage (CVD) and amygdalohippocampal complex (AHC) atrophy, as revealed by scalp electroencephalography (EEG) in a cohort of subjects with mild cognitive impairment (MCI). All MCI subjects underwent EEG recording and magnetic resonance imaging. EEGs were recorded at rest. Relative power was separately computed for delta, theta, alpha1, alpha2, and alpha3 frequency bands. In the spectral band power the severity of CVD was associated with increased delta power and decreased alpha2 power. No association of vascular damage was observed with alpha3 power. Moreover, the theta/alpha1 ratio could be a reliable index for the estimation of the individual extent of CV damage. On the other side, the group with moderate hippocampal atrophy showed the highest increase of alpha2 and alpha3 power. Moreover, when the amygdalar and hippocampal volumes are separately considered, within amygdalohippocampal complex (AHC), the increase of theta/gamma ratio is best associated with amygdalar atrophy whereas alpha3/alpha2 ratio is best associated with hippocampal atrophy. CVD and AHC damages are associated with specific EEG markers. So far, these EEG markers could have a prospective value in differential diagnosis between vascular and degenerative MCI.

Music, music therapy and dementia: a review of literature and the recommendations of the Italian Psychogeriatric Association.

This study reviews the most recent (from 2000 to 2011) Clinical Controlled Trials (CCT) and Randomized Controlled Trials (RCT) concerning the use of music and music-therapy (MT) in the context of dementia and related issues. Studies which explored the efficacy of music and MT on behavioral and psychological symptoms of dementia (BPSD) are prevalent, while those aiming at assessing a potential effect of these approaches on cognitive and physiological aspects are scant. Although with some limitations, the results of these studies are consistent with the efficacy of MT approach on BPSD. In this context, the ability of the music therapist to directly interact with the patients appears to be crucial for the success of the intervention. This review was endorsed by the Italian Psychogeriatric Association (AIP) and represents its view about the criteria to select appropriate music and MT approaches in the field of dementia. Accordingly, we have developed a list of recommendations to facilitate the current use of these techniques in the context of non-pharmacological treatments for patients with dementia.

Specific EEG changes associated with atrophy of hippocampus in subjects with mild cognitive impairment and Alzheimer's disease.

We evaluated the association between hippocampal atrophy and increase of the EEG markers alpha3/alpha2 relative power ratio in mild cognitive impairment (MCI) and Alzheimer's disease patients. Seventy-nine subjects with MCI and 11 patients with AD underwent EEG recording and MRI scan. The MCI group was subdivided in three subgroups according to growing hippocampal atrophy. The groups were characterized by alpha3/alpha2 relative power ratio. In AD patients group mapped hippocampal regions were computed and related with alpha3/alpha2 power ratio. Results show that the increase of alpha3/alpha2 power ratio is correlated with atrophy of hippocampus both in MCI and in Alzheimer's disease patients. This finding confirms the possible diagnostic role of EEG markers as diagnostic and prognostic factors in patient with prodromal and declared Alzheimer's disease.

Prefrontal cortex rTMS enhances action naming in progressive non-fluent aphasia.

BACKGROUND AND PURPOSE: Progressive non-fluent aphasia (PNFA) is a neurodegenerative disorder that is characterized by non-fluent speech with naming impairment and grammatical errors. It has been recently demonstrated that repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) improves action naming in healthy subjects and in subjects with Alzheimer's disease. PURPOSE: To investigate whether the modulation of DLPFC circuits by rTMS modifies naming performance in patients with PNFA. METHODS: Ten patients with a diagnosis of PNFA were enrolled. High-frequency rTMS was applied to the left and right DLPFC and the sham (i.e. placebo) condition during object and action naming. A subgroup of patients with semantic dementia was enrolled as a comparison group. RESULTS: A repeated-measure anova with stimulus site (sham, left and right rTMS) showed significant effects. Action-naming performances during stimulation of both the left and right DLPFC were better than during placebo stimulation. No facilitating effect of rTMS to the DLPFC on object naming was observed. In patients with a diagnosis of semantic dementia, no effect of stimulation was reported. CONCLUSIONS: Our study demonstrated that rTMS improved action naming in subjects with PNFA, possibly due to the modulation of DLPFC pathways and a facilitation effect on lexical retrieval processes. Future studies on the potential of a rehabilitative protocol using rTMS applied to the DLPFC in this orphan disorder are required.

EEG markers are associated to gray matter changes in thalamus and basal ganglia in subjects with mild cognitive impairment.

BACKGROUND: Gray matter (GM) changes of thalamus and basal ganglia have been demonstrated to be involved in Alzheimer's disease (AD). Moreover, the increase of two EEG markers, alpha3/alpha2 and theta/gamma ratio, have been associated with, respectively, AD converter and non-AD converter subjects with mild cognitive impairment (MCI). OBJECTIVE: To study the association of prognostic EEG markers with specific GM changes of thalamus and basal ganglia in subjects with MCI to identify different MCI populations. METHODS: 74 adult subjects with mild cognitive impairment underwent EEG recording and high resolution 3D magnetic resonance imaging (MRI). The theta/gamma and alpha3/alpha2 ratio was computed for each subject. Three groups were obtained according to increasing tertile values of both alpha3/alpha2 and theta/gamma ratio. Gray matter density differences between groups were investigated using a voxel-based morphometry technique. RESULTS: Subjects with higher a3/a2 ratios when compared to subjects with lower and middle a3/a2 ratios showed minor atrophy in the ventral stream of basal ganglia (head of caudate nuclei and accumbens nuclei bilaterally) and of the pulvinar nuclei in the thalamus; subjects with higher t/g ratio showed minor atrophy in putamina nuclei bilaterally than subjects with middle ratio. CONCLUSION: The integrated analysis of EEG and morpho-structural markers could be useful in the comprehension of anatomo-physiological underpinning of the MCI entity.

Volumetric differences in mapped hippocampal regions correlate with increase of high alpha rhythm in Alzheimer's disease.

Objective. The increase of high alpha relative to low alpha power has been recently demonstrated as a reliable EEG marker of hippocampal atrophy conversion of patients with mild cognitive impairment (MCI) in Alzheimer's disease (AD). In the present study we test the reliability of this EEG index in subjects with AD. Methods. Correlation between EEG markers and volumetric differences in mapped hippocampal regions was estimated in AD patients. Results. Results show that the increase of alpha3/alpha2 power ratio is correlated with atrophy of mapped hippocampal regions in Alzheimer's disease. Conclusions. The findings confirm the possible diagnostic role of EEG markers.

MCI patients' EEGs show group differences between those who progress and those who do not progress to AD.

The theta/gamma and alpha3/alpha2 ratio were investigated as early markers for prognosticating of progression to dementia. 76 subjects with mild cognitive impairment (MCI) underwent EEG recording, MRI scans and neuropsychological (NPS) tests. After 3 years of follow-up, three subgroups were characterized as converters to Alzheimer's disease (AD, N=18), converters to non-AD dementia (N=14) and non-converters (N=44). The theta/gamma and alpha3/alpha2 ratio, performance on cognitive tests and hippocampal volume, as evaluated at the time of initial MCI diagnosis, were studied in the three groups. As expected, MCI to AD converters had the smallest mean hippocampal volume and poorest performance on verbal learning tests, whereas MCI to non-AD converters had poorest cognitive performance in non-verbal learning tests, abstract thinking, and letter fluency. Increased theta/gamma ratio was associated with conversion to both AD and non-AD dementia; increased alpha3/alpha2 ratio was only associated with conversion to AD. Theta/gamma and alpha3/alpha2 ratio could be promising prognostic markers in MCI patients. In particular, the increase of high alpha frequency seems to be associated with conversion in AD. EEG markers allow a mean correct percentage of correct classification up to 88.3%. Future prospective studies are needed to evaluate the sensitivity and specificity of these measures for predicting an AD outcome.

The new Alzheimer's criteria in a naturalistic series of patients with mild cognitive impairment.

To test the validity of the new diagnostic criteria for Alzheimer's disease (AD) in a naturalistic series of patients with mild cognitive impairment (MCI). Ninety consecutive MCI patients were enrolled in a longitudinal study on the natural history of cognitive impairment. Medial temporal (MT) atrophy on MRI was defined as hippocampal volume below the fifth percentile of the distribution in healthy elders, abnormal CSF was based on Sjogren's cutoffs for Abeta42 and tau, and temporoparietal hypometabolism on 18F-FDG PET based on Herholz's t sum score. Patients were followed clinically to detect conversion to AD (MCI-AD), non-AD dementia (MCI-nAD), or no conversion (MCI-NC). The 24 MCI-AD and 15 MCI-nAD patients had sociodemographic, clinical, and neuropsychological baseline features similar to the 51 MCI-NC patients. All MCI patients with MT atrophy converted to AD, as did all those with abnormal CSF, but only 48 and 35% of those without MT atrophy or abnormal CSF converted (p on logrank test = 0.0007 and 0.001). Prediction of AD conversion was enhanced when positivity to either MT atrophy or abnormal CSF was considered, with only 15% of those MCI patients negative on both converting to AD (p < 0.0005). Markers were not predictive of non-AD dementia conversion. The accuracy of either MT atrophy or abnormal CSF in discriminating MCI-AD from MCI-NC was good (AUC 0.82, 95% CI 0.70-0.95). MT atrophy and abnormal CSF are the single most robust predictors of conversion to AD in MCI patients, and their combination enhances prediction. AD markers are not predictive of conversion to non-AD dementia.

EEG markers discriminate among different subgroup of patients with mild cognitive impairment.

Aim of the study is to discriminate among participants with mild cognitive impairment through electroencephalography brain rhythms. A total of 79 participants with MCI were classified into 4 subgroups based on the beginning of memory complaints up to the time of first visit. All participants underwent electroencephalography recording, magnetic resonance imaging, apolipoprotein E characterization, and volumetric morphometry estimation of hippocampal region. Electroencephalography markers show 2 distinct patterns: (1) increase of theta/ delta power ratio and highest value of alpha2 band power in the group with shorter duration of disease, the greater right-left hippocampal volume difference and worst memory performance; (2) the highest value of alpha3 band power and the highest alpha3/alpha2 power ratio in the group with the lesser total hippocampal volume but preserved memory performance. Apolipoprotein E4 is linked to a major risk of early beginning of disease. Electroencephalography markers allow a mean correct percentage of correct classification up to 89%.

Needs of caregivers of the patients with dementia.

This study was conducted to isolate the needs families express both for medical and psychological care, and for educational and social support in 112 caregivers of patients affected by moderate to severe dementia (mini mental state examination=MMSE score: 9+/-7) consecutively recruited at our Memory Clinic, to develop approaches as individualized as possible. The medical needs caregivers express are mainly relative to a better knowledge of the disease (78%) and the exact diagnosis (65%); the education-related needs are mainly relative to the acquisition of communicational skills (83%) and the optimal handling of cognitive (77%) and behavioral disorders (81%); the psychological ones mainly concern the area of assistance induced emotional stress management (37%) and the elaboration of feelings such as anxiety, rage and guilt (49%). Variance analysis shows a correlation between emotional caregivers' needs and the subjective and objective burdens they carry. Despite the attention to the role families play in caring for patients with a diagnoses of moderate to severe dementia, caregivers still express low levels of illness-consciousness and high levels of psychological discomfort. A lot more ought to be done in order to provide better information about the disease, about appropriate cognitive and behavioral disorder management skills, and about viable psychological support.

Life expectancy in Alzheimer's disease (AD).

Survival following a diagnosis of AD is important information for health planners, caregivers, patients, and their families. AD is associated with variable, but shortened life expectancy. Knowing the expected survival time may empower people with AD and their families, but clinicians currently have limited predictive information. A better knowledge about prognosis in patients affected by AD and related disorders should be of paramount importance in order to improve care plans and assist in medical decisions, above all for patients in the moderate-severe stages of the disease. Life expectancy for patients with AD can vary between 3 to 10 years. Many studies have tried to identify predictive factors that can be of help for clinicians. The main predictor of life expectancy is the age. Therefore caregivers, patients, and their families could plan on a median life span as long as 7 to 10 years for patients whose conditions are diagnosed when they are in their 60s and early 70s, to only about 3 years or less for patients whose conditions are diagnosed when they are in their 90s. Dementias with prominent psychiatric-behavioral manifestations and gait impairment have a faster progression compared to AD. However the many variables that influence life expectancy make difficult to define prognosis at the bedside and more studies are needed to assist clinicians in they daily routine with patients and caregivers.

Increase of theta/gamma ratio is associated with memory impairment.

OBJECTIVE: In this study the theta/gamma ratio was investigated as early marker of cognitive decline. METHODS: Forty-nine subjects with mild cognitive impairment (MCI) underwent EEG recording and MRI scan. The theta/gamma ratio of the relative power at the peak frequency was computed. Based on the tertiles values of the ratio, three groups with increasing values of theta/gamma ratio were obtained. The groups were characterized by the performance on cognitive tests. Changes in functional brain connectivity, as expressed by interhemisperic and intrahemispheric EEG linear coherence in the groups were also evaluated. RESULTS: Increase in theta/gamma ratio was associated with impairment in memory tests. This relationship was confirmed by correlation and multiple regression analysis. An independent association was found between theta/gamma ratio and alpha3/alpha2 power ratio. Coherence analysis showed modifications of interhemispheric functional coupling on temporal regions on slow frequencies. CONCLUSIONS: Theta/gamma ratio of relative power at peak frequency is significantly associated to memory decline. It could be a useful tool in detecting MCI subjects which are at major risk to develop Alzheimer's disease (AD) or other dementias. SIGNIFICANCE: A global modulation of brain rhythms could be driven by the pathological alterations of theta/gamma ratio.

Transcranial magnetic stimulation improves naming in Alzheimer disease patients at different stages of cognitive decline.

OBJECTIVE: Word-finding difficulty (anomia) is commonly observed in Alzheimer's dementia (AD). The aim of this study was to assess the effect of repetitive transcranial magnetic stimulation (rTMS) applied to the dorso-lateral prefrontal cortex (dlPFC) on picture naming in 24 probable AD patients with different degrees of cognitive decline. METHODS: High-frequency rTMS was applied to the left and right dlPFC during object and action naming in AD patients. A sham stimulation was used as a control condition. RESULTS: Whilst, as previously reported, stimulation to both the left and the right dlPFC improved action, but not object naming in the mild AD group; an improved naming accuracy for both classes of stimuli was found in the moderate to severe group. CONCLUSIONS: Repetitive transcranial magnetic stimulation applied to the dlPFC improves naming performance also in the advanced stages of AD. Moreover, in the severe group the effect is not specific for action naming, as in the case of the mild AD group. These findings suggest that rTMS can affect the intrinsic ability of the brain to restore or compensate for damaged function and may represent an useful new tool for cognitive rehabilitation.

The contribution of TMS to frontotemporal dementia variants.

OBJECTIVE: Frontotemporal lobar degeneration (FTLD) includes different heterogeneous conditions mainly characterized by personality changes and cognitive deficits in language and executive functions; movement disorders have also been associated with FTLD. The present study aimed to measure the primary motor cortex (M1) inhibitory and facilitatory functions in patients affected by FTLD. MATERIALS AND METHODS: The study included 17 FTLD patients, 8 age-matched healthy controls and 8 Alzheimer's disease (AD) patients. Transcranial magnetic stimulation (TMS) was used to study intracortical inhibition (ICI) and facilitation (ICF) by using a double-pulse paradigm. RESULTS: FTLD patients were comparable with controls and AD patients for ICI and ICF. Corticobasal degeneration (CBD) patients presented significant reduced inhibition at ISI3; moreover two out of seven CBD patients had only ipsilateral responses. DISCUSSION: The present study reveals a selective impairment of M1 ICI inhibitory response in CBD, which may help in distinguishing among the FTLD clinical spectrum.

Serum leptin levels are higher in females affected by frontotemporal lobar degeneration than Alzheimer's disease.

Frontotemporal lobar degeneration (FTLD) includes different heterogeneous conditions, mainly characterised by personality changes, along with cognitive deficits in language and executive functions. Movement disorders are variably represented. Behavioural disturbances constitute the core feature of FTLD, and eating disorders represent one of the most distinguishing symptoms between FTLD and Alzheimer's disease (AD). The biochemical correlates of such dysfunctions remain to be defined. The adipocyte derived hormone leptin is known to play a foundamental role in food intake and energy balance. To understand whether leptin could be involved in FTLD eating abnormalities, we measured serum leptin levels in 59 patients with FTLD compared with 25 with AD. Serum leptin levels in patients with FTLD were comparable with those in patients with AD. Nevertheless, females with FTLD showed significantly higher leptin levels compared with females with AD. No difference was found between FTDL and AD males or within the spectrum of patients with FTLD. Hyperphagic FTLD females showed higher circulating leptin levels in comparison with those without eating abnormalities; no differences were found between males with FTLD with respect to serum leptin and food intake disturbances. The present study showed a selective gender difference in leptin levels between females with FTLD and AD, which may suggest specific cognitive and behavioural networks need to be investigated.