Analysis of video-polysomnographic sleep findings in dementia with Lewy bodies.

Knowledge of sleep architecture and disorders of nocturnal sleep in dementia with Lewy bodies (DLB) is limited by a lack of systematic video-polysomnographic (video-PSG) investigations. We describe video-PSG findings in 29 consecutive subjects diagnosed with DLB. All the patients underwent a clinical interview and overnight video-PSG monitoring. Twenty-nine nondemented patients with Parkinson's disease (PD) matched for age and sex with the DLB cases were selected for comparison. The DLB subjects showed less 1NREM sleep (P = .000) and more 2NREM sleep (P = .000) than the PD subjects. Sleep apnea (30.7% vs. 34.8%) and periodic limb movements (60.9% versus 50.0%) were frequent in both groups. Disruptive motor behavioral manifestations were more frequent in subjects with DLB (69.6% vs. 26.9%, P = .008) and consisted of not only REM sleep behavior disorder (RBD) but also confusional events (30.3% vs. 3.8%, P = .020) and arousal-related episodes mimicking RBD. Subjects with DLB in whom a sleep disturbance had been the presenting symptom performed better than those with other onset symptoms on both the Mini-Mental State Examination (22.2 ± 4.1 vs. 18.1 ± 4.6, P = .019) and the Frontal Assessment Battery (15.8 vs. 10.3, P = .010). Polysomnographic findings in DLB show a complex mix of overlapping sleep alterations: impaired sleep structure, sleep comorbidities, and various motor-behavioral events (not restricted to RBD). Clinicians should be aware of the possibility of misleading symptoms and of the risk of overlooking sleep comorbidities, and consider performing polysomnographic sleep investigations in selected cases. We found evidence that a sleep disturbance as the presenting symptom might indicate a different phenotype of the disease, characterized by milder cognitive impairment.

Memantine in Alzheimer's disease: experience in an Alzheimer's disease assessment unit.

BACKGROUND AND AIMS: Memantine is an uncompetitive N-methyl-D-aspartate receptor antagonist. Clinical and observational studies have demonstrated its efficacy on both cognitive and behavioral symptoms of moderate-to-severe Alzheimer's disease (AD) and described its good safety and tolerability profile. We report here our experience with memantine in patients with AD during a two-year follow-up. METHODS: From June 2005 to May 2010, memantine was given to 201 outpatients with moderate-to-severe AD: 93 patients were concomitantly receiving treatment with acetyl cholinesterase inhibitors (AChEIs) (Group 1) and the other 108 were prescribed memantine as monotherapy (Group 2). All patients were administered the following scales: Mini Mental State Examination, Activities of Daily Living, Instrumental Activities of Daily Living, Neuropsychiatric Inventory. We report the results of followup assessments conducted at six months and 1, 2 and 3 years. RESULTS: Sixteen patients (8%) stopped treatment within the first month because of side-effects. In each group, about 20% of subjects showed no deterioration at six months and 1 year, and this proportion decreased only slightly at 2 years. Higher NPI scores at baseline and psychotropic drug use emerged as factors significantly related to reduced response to treatment (p<0.01). CONCLUSIONS: Results confirmed the short-term effect of memantine, both in monotherapy and in combination with AchEIs in moderate-to-severe AD. This efficacy, albeit slight, was found to persist in the longer term.

REM and NREM sleep enactment behaviors in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies.

BACKGROUND/OBJECTIVE: Nocturnal sleep enactment behaviors (SEBs) are common in patients affected by Parkinson's disease (PD), dementia associated with Parkinson's disease (PDD), and dementia with Lewy bodies (DLB). We investigated the occurrence and neurobiological significance of abnormal SEBs in the context of PD without cognitive decline compared to PDD/DLB patients. METHODS: We evaluated a sample of 139 patients with PD, PDD, or DLB in a cross-sectional survey. One hundred and seventeen patients showing either no cognitive impairment (PD group) or meeting the diagnostic requirements for dementia (PDD/DLB group) underwent video-polysomnography. Seventy subjects (42 males) in whom a clear-cut diagnosis of abnormal sleep-related motor-behavioral episodes was possible were included in the final analysis. RESULTS: SEBs consisting of RBD or occurring on arousal from NREM or REM sleep were globally more frequent in the dementia group (PDD/DLB) than in the PD group (p=0.001), the difference being statistically significant for arousal-related episodes (p=0.002), while a trend emerged for RBD (p=0.07). Male sex, daytime sleepiness, higher motor impairment, and lower mini-mental score were significantly more frequent with the occurrence of abnormal sleep-related motor-behavioral episodes. CONCLUSION: SEBs in PD, PDD, and DLB may consist of RBD episodes or of arousal-related NREM and REM episodes. These latter are more frequent in patients with PDD/DLB and seem to be mainly related to more advanced stages of disease with a higher degree of cognitive decline.

Caregiver burden and coping in early-stage Alzheimer disease.

This study was set out to describe caregiver-perceived burden and coping in early-stage Alzheimer disease (AD). A total of 163 consecutive pairs of patients with AD and their principal caregivers were initially recruited. The caregivers completed the Caregiver Burden Inventory (CBI) and the Coping Orientations to Problems Experienced scale, and also provided sociodemographic information; the patients with AD were assessed by means of the Mini Mental State Examination and the Neuropsychiatric Inventory. Data from 126 patient-caregiver pairs were analyzed. The caregivers (mean age 56.11±12.37 y) were mainly women (76%); 64% were the patient's offspring; 39% lived with the patient. From the CBI data, it emerged that caregivers perceived loss of personal time (objective burden, 33%) and the feeling of missing out on opportunities (developmental burden, 25%) as their main stressors. Total CBI score was negatively correlated with Mini Mental State Examination (P=0.005). As regards coping strategies, the caregivers predominantly used problem-oriented strategies associated with a positive attitude. The use of dysfunctional strategies was predictive of caregiver burden. It is important to be aware that avoidance and dysfunctional coping strategies predispose caregivers of patients with AD to higher level of distress, whereas successful caregiving seems to be based on the use of problem-oriented strategies early in the disease when solutions are still available.

The effects of alcohol on cognition in the elderly: from protection to neurodegeneration.

The effects of chronic alcohol abuse on cognition are well known. Memory and executive functions appear to be the cognitive domains primarily impaired, and prefrontal and frontal damage is reported on neuroimaging studies both at micro- and macrostructural levels. Abstinence can partially reverse these alterations through mechanisms of neuroplasticity. Alcohol acts in a dose-dependent fashion, and a light-to-moderate consumption indeed has protective effects on cardiovascular risk factors and promotes anti-inflammatory and anti-oxidative processes. In the elderly on such a regimen, several epidemiological studies have reported a decreased risk of both coronary and cerebrovascular disease and of dementia. However, because of data heterogeneity and the presence of several confounding variables, further studies are needed to clarify these findings. In addition, the complexity of alcohol neurobiology (interaction of alcohol effects with genetic predisposition and environmental factors) and the occurrence of age-related changes should also be taken into account. As dementia, stroke and cardiovascular disease are the leading causes of mortality in older people in developed countries, a better knowledge of the mechanisms underlying the effects of alcohol intake may be helpful from the perspective not only of medical management but also of social health policy.

Differences between physician and caregiver evaluations in Alzheimer's disease.

In Alzheimer's disease (AD) differences are often reported between caregivers' and physicians' aims and evaluations. The aim of this study was to investigate the presence of discrepancies between the evaluations of caregivers and physicians. Two hundred and eighteen caregivers of outpatients diagnosed with mild-to-moderate AD, referred to our Alzheimer's Disease Assessment Unit, entered the study. Caregiver burden was investigated using the Caregiver Burden Inventory (CBI) and the Neuropsychiatric Inventory Caregiver Distress Scale (NPIDS). Caregivers were also administered a four-point scale to assess quantitatively whether their expectations in relation to the efficacy of the pharmacological treatment had been satisfied and a scale exploring clinical global impression of change. Caregivers whose expectations had not been satisfied had significantly higher CBI and NPIDS scores and a lower level of education; moreover, caregivers tended to overestimate the degree of cognitive decline during the course of the disease. These results underline the importance of correct and constant communication with AD patients and their families.

Report of ten years' activity in an Alzheimer's disease assessment unit.

BACKGROUND AND AIMS: After ten years' treatment with cholinesterase inhibitors (AcheI) in Alzheimer's disease (AD), we report here the activity of the Alzheimer's Disease Assessment Unit of IRCCS C. Mondino, Pavia, Italy. METHODS: From September 2000 to December 2007, 794 out-patients (of 2236 referred to our Assessment Unit for cognitive disturbances) with AD of mild to moderate degree were treated with cholinesterase inhibitors (M/F: 273/521, mean age 73.6+/- 8.4 yrs, range 52-85 yrs). Outcome measures were scores on Mini Mental State Examination (MMSE), ADL, IADL and Neuropsychiatric Inventory (NPI). RESULTS: Mean treatment duration was 36.9+/-16.1 months. After three months' treatment, MMSE scores remained stable (responders) in 60% of cases and improved (increase of 3 or more points - good responders) in 15%, with good preservation of autonomy. After 15 months, the percentage of "good responders" decreased to 7%, while after 15, 27 and 39 months the percentage of responders progressively decreased to 40%, 30% and 8%, respectively; greater impairment in instrumental with respect to basic everyday activities was noted. No variables capable of predicting the response to treatment were detected. The onset of behavioral disturbances caused significant (p<0.02) worsening of both cognition and function and, in 12% of cases, suspension of treatment. CONCLUSIONS: Our results therefore confirm the efficacy of AcheI in AD of mild to moderate degree even in a nonselected population; efficacy also seems to persist in long-term treatment. This report, although brief and mainly descriptive, can make a contribution to better knowledge of the usefulness of these drugs in AD of mild to moderate extent in everyday clinical practice.

Deep brain stimulation and cognitive functions in Parkinson's disease: A three-year controlled study.

There is debate over the cognitive and behavioral effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD). To evaluate these effects, we performed a prospective, naturalistic controlled, 3-year follow-up study. A total of 65 PD patients were enrolled, of whom 32 underwent STN-DBS (PD-DBS) and 33, even though eligible for this treatment, declined surgery and chose other therapeutic procedures (PD-control). Motor and neuropsychological functions were assessed in all the subjects at baseline (T0) and 36 months (T36). The PD-DBS patients were also evaluated at 1, 6, 12, and 24 months after surgery (T1, T6, T12, and T24). At T1, compared with T0, the PD-DBS patients recorded worse logical executive function task and verbal fluency (FAS) scores, whereas their performance of memory tasks remained stable. At T12, their cognitive profile had returned within the pre-DBS range, thereafter remaining stable until T36. FAS scores at T36 were significantly worse in the PD-DBS compared with the PD-control patients. This is the first long-term naturalistic controlled study of cognitive functions in PD patients submitted to STN-DBS. Our results confirm previous reports of a worsening of verbal fluency after DBS, but show that STN-DBS seems to be relatively safe from a cognitive standpoint, as the short-term worsening of frontal-executive functions was found to be transient.

REM behavior disorder, hallucinations and cognitive impairment in Parkinson's disease: a two-year follow up.

In Parkinson's disease (PD) the presence of REM parasonnias as REM Behaviour Disorder (RBD) or vivid dreams/nightmares, is recognized as largely associated with hallucinations, even if the risk of the development of hallucinations seem not to depend on how long the REM parasomnias had been occurring. The aim of this study was to establish if RBDs occurring earlier than hallucinations in PD are predictive of cognitive impairment development. Three groups of PD patients: i) group 1, without RBD and without hallucinations; ii) group 2, with RBD but without hallucinations; iii) group 3, with RBD and hallucinations have been prospectively investigated at baseline and after two years throughout a clinical and neuropsychological evaluation. After two years, the group 1 continued to present normal neuropsychological tests and did not present either RBDs or hallucinations. In the group 2, the frontal impairment evidenced at baseline was confirmed; the onset of newly hallucinations was reported in a subgroup of 12 patients, who proved to be older, with a more severe executive impairment at baseline and with a more severe motor symptoms progression than those RBD patients who had not manifested hallucinations. The group 3, characterized at baseline by a more severe cognitive impairment presented, after two years, a cognitive worsening and a higher mortality rate. The longitudinal but at preliminary step investigation identified a PD subgroup of patients, in whom a common background disease profile, including the presence of RBD, could represent a "red flag" in developing further cognitive impairment.

Cognitive performance in REM sleep behaviour disorder: a possible early marker of neurodegenerative disease?

BACKGROUND: Rapid eye movement [REM] sleep behaviour disorder (RBD) may herald neurodegenerative diseases. Neurobiological deficits similar to those identified in neurodegenerative diseases have been reported in idiopathic RBD. Researchers are looking for early markers supporting a possible role of RBD as a harbinger of impending neurodegenerative disease. OBJECTIVE: To examine the neuropsychological functions in idiopathic RBD subjects. Should they be found to present a neuropsychological dysfunction that overlaps that reported in neurodegenerative diseases, it would be possible to consider cognitive deficits as possible early markers of an underlying degenerative process. METHODS: Twenty-three subjects with idiopathic RBD (21 males, mean age 67.0+/-7.0 years) and a group of healthy controls matched for sex, age and education underwent a neuropsychological battery evaluating different cognitive domains. FINDINGS: Considering mean values, poorer performances were observed in the Word Span (p<.001), Rey-Osterrieth's complex figure recall (p=.003), Digit Span (p=.003) and Logic Memory (p=.003) tests. On the basis of equivalent scores, the RBD subjects performed significantly more poorly on tests of visuo-constructional learning abilities (p<.001). INTERPRETATION: Our data show the possible presence of cognitive deficits in RBD defined as idiopathic, sharing common features in particular with Lewy body disease. Neuropsychological evaluation in RBD could lead to presymptomatic identification of neurodegenerative disease, but until more prolonged long-term follow-up data are available, the true neurobiological significance of cognitive deficits in RBD will remain unknown.