Longitudinal changes in quality of life among elderly people with and without dementia.

ABSTRACTObjective:To study longitudinal changes in the quality of life (QoL) in persons with and without dementia, and explore the factors associated with baseline QoL and changes of QoL over the follow-up period. DESIGN: Prospective longitudinal study. SETTING: Data were collected from 17 municipalities in Norway in the period from January 2009 to August 2012. A total of 412 persons were included, 254 (61.7 %) persons without dementia and 158 (38.3 %) with dementia at baseline. SUBJECTS: Persons 70 years of age or older, receiving municipal care services. Main outcome measures include the following: self-rated and proxy-rated QoL over a period of 18 months, cognitive status, functional status, neuropsychiatric symptoms, and demographics. RESULTS: Longitudinal changes in QoL were small, despite changes in clinical variables. Proxy ratings of patients QoL were lower than the patients' own ratings. Belonging to a group with low QoL trajectory was associated with symptoms of depression, reduced physical and instrumental functioning, and more severe dementia. CONCLUSION: Patients and proxies evaluated the patients' QoL differently and QoL did not necessarily correspond with deterioration in clinical parameters. To prevent impaired QoL, we need to address identified factors and keep an approach open to the individual perceptions of QoL.

Does increased physical activity in school affect children's executive function and aerobic fitness?

This study seeks to explore whether increased PA in school affects children's executive function and aerobic fitness. The "Active school" study was a 10-month randomized controlled trial. The sample included 449 children (10-11 years old) in five intervention and four control schools. The weekly interventions were 2×45 minutes physically active academic lessons, 5×10 minutes physically active breaks, and 5×10 minutes physically active homework. Aerobic fitness was measured using a 10-minute interval running test. Executive function was tested using four cognitive tests (Stroop, verbal fluency, digit span, and Trail Making). A composite score for executive function was computed and used in analyses. Mixed ANCOVA repeated measures were performed to analyze changes in scores for aerobic fitness and executive function. Analysis showed a tendency for a time×group interaction on executive function, but the results were non-significant F(1, 344)=3.64, P=.057. There was no significant time×group interaction for aerobic fitness. Results indicate that increased physical activity in school might improve children's executive function, even without improvement in aerobic fitness, but a longer intervention period may be required to find significant effects.

Progression and survival in Parkinson's disease with subthalamic nucleus stimulation.

BACKGROUND: Treatment for Parkinson's disease (PD) is symptomatic. Surgical treatment with continuous high-frequency stimulation of the subthalamic nucleus (STN-DBS) is established as a safe symptomatic treatment with long-term beneficial effects. It has been postulated that STN-DBS could halt the progression of PD through a disease modifying or neuroprotective effect. OBJECTIVE: To investigate the postulated disease modifying or neuroprotective effect of STN-DBS by comparing the rate of deterioration of parkinsonism and mortality over time in two selected and matched groups of patients with PD with and without surgery. METHODS: Group A was derived from all patients who received STN-DSB surgery at Oslo University Hospital, from January 2001 to December 2007. Group B was derived from a prevalence study of PD in the Stavanger area of Western Norway in 1993. The two groups were individually matched and the disease progression measured by Unified Parkinson's Disease Rating Scale-motor scores, and the mortality was compared. RESULTS: The mean annual change based on baseline and last observation scores in individually matched groups was 0.97 (SD = 3.57) for the surgery group and 1.04 (SD = 3.33) for the controls and thus not significantly different, F(1, 104) = .21, P = 0.89. The long-term mortality was also similar in the two groups during long-term follow-up, hazard ratio = 1.76, CL 0.91-3.40, P = 0.091. CONCLUSION: This study gives no support to a postulated disease modifying or neuroprotective effect of STN-DBS in patients with PD.

Mild cognitive impairment in drug-naive patients with PD is associated with cerebral hypometabolism.

OBJECTIVE: To characterize brain metabolic changes associated with mild cognitive impairment (MCI) in drug-naive patients with Parkinson disease (PD) using (18)F-fluorodeoxyglucose (FDG) and PET (FDG-PET). METHODS: This cross-sectional study included newly diagnosed patients with PD with MCI in single or multiple domain (PD-MCI; n =12) and without MCI (PD-nMCI; n =12), and healthy controls (n =12). The groups were matched for age. Moreover, the patient groups were matched for motor disability. All subjects underwent a FDG-PET study. Cerebral regional relative metabolic maps were compared in PD-MCI, PD-nMCI, and controls using regions of interest analysis (ROIs) and voxel-based analysis with statistical parametric mapping. RESULTS: ROIs and voxel-based analyses revealed significant relative hypometabolism in the prefrontal, superior/inferior parietal, and associative occipital cortices as well as in the striatum in patients with PD-MCI relative to controls (p < 0.05) and to a lesser extent in patients with PD-nMCI. In contrast, patients with PD-nMCI did not show significant metabolic changes as compared to controls. CONCLUSION: MCI in patients with PD is associated with cortical hypometabolism since the earliest stage, independent of therapy or motor disability. The early involvement of posterior cortical region, a pattern shared by advanced stages of PD-MCI and PD with dementia, could represent an early marker of dementia. The relevance of this pattern in predicting prodromal dementia has to be evaluated in longitudinal studies.

Mild cognitive impairment in Parkinson disease: a multicenter pooled analysis.

BACKGROUND: In studies of mild cognitive impairment (MCI) in Parkinson disease (PD), patients without dementia have reported variable prevalences and profiles of MCI, likely to be due to methodologic differences between the studies. OBJECTIVE: The objective of this study was to determine frequency and the profile of MCI in a large, multicenter cohort of well-defined patients with PD using a standardized analytic method and a common definition of MCI. METHODS: A total of 1,346 patients with PD from 8 different cohorts were included. Standardized analysis of verbal memory, visuospatial, and attentional/executive abilities was performed. Subjects were classified as having MCI if their age- and education-corrected z score on one or more cognitive domains was at least 1.5 standard deviations below the mean of either control subjects or normative data. RESULTS: A total of 25.8% of subjects (95% confidence interval [CI] 23.5-28.2) were classified as having MCI. Memory impairment was most common (13.3%; 11.6-15.3), followed by visuospatial (11.0%; 9.4-13.0) and attention/executive ability impairment (10.1%; 8.6-11.9). Regarding cognitive profiles, 11.3% (9.7-13.1) were classified as nonamnestic single-domain MCI, 8.9% (7.0-9.9) as amnestic single-domain, 4.8% (3.8-6.1) as amnestic multiple-domain, and 1.3% (0.9-2.1) as nonamnestic multiple-domain MCI. Having MCI was associated with older age at assessment and at disease onset, male gender, depression, more severe motor symptoms, and advanced disease stage. CONCLUSIONS: MCI is common in patients with PD without dementia, affecting a range of cognitive domains, including memory, visual-spatial, and attention/executive abilities. Future studies of patients with PD with MCI need to determine risk factors for ongoing cognitive decline and assess interventions at a predementia stage.

The spectrum of neuropsychiatric symptoms in patients with early untreated Parkinson's disease.

BACKGROUND: Neuropsychiatric symptoms are common in Parkinson's disease (PD) and have important clinical consequences for patients, caregivers and society. Few studies of neuropsychiatric symptoms in early untreated PD exist. OBJECTIVE: To explore the range, clustering and correlates of neuropsychiatric symptoms in an incidence cohort of untreated subjects with PD. METHODS: All cases with incident PD identified during a 22 month period in four counties of Western and Southern Norway were included. Standardised criteria were used to diagnose PD. The Neuropsychiatric Inventory (NPI) was administered to 175 PD and 166 healthy control subjects with similar age and sex distributions. Cluster analysis was used to investigate the interrelationship of NPI items. RESULTS: The proportion with any NPI symptoms was higher in PD (56%) than in controls (22%) (p<0.001). Depression (37%), apathy (27%), sleep disturbance (18%) and anxiety (17%) were the most common symptoms. Clinically significant symptoms occurred in 27% of the PD group compared with only 3% in the control group (p<.001). Subjects with clinically significant neuropsychiatric symptoms had more severe parkinsonism than those without. Two neuropsychiatric clusters were identified, one characterised by mood symptoms and one by apathy. CONCLUSIONS: Although the majority of patients with early untreated PD do not have clinical significant neuropsychiatric symptoms, these symptoms are more common in patients than in people without PD. Both psychological stress and brain changes associated with PD are likely to contribute to the higher frequencies.

Cognitive impairment in incident, untreated Parkinson disease: the Norwegian ParkWest study.

BACKGROUND: Little is known regarding the cognitive impairment in subjects with early, drug-naïve Parkinson disease (PD). The aim of this study was to explore the proportion with mild cognitive impairment (MCI) and subtypes in an incidence cohort of untreated PD in Southern and Western Norway. METHODS: A total of 196 non-demented, drug-naive patients who were recruited after an extensive search of all new cases of PD in the area and 201 healthy control subjects completed a battery of neuropsychological tests of verbal memory, visuospatial, and attentional-executive functioning. Subjects were classified as MCI if the age- and education-corrected z-score was falling 1.5 standard deviations below the mean for at least one of the cognitive domains. RESULTS: The PD group was more impaired on all neuropsychological tests than controls, but the effect sizes were small. The largest effect size was found for verbal memory. A total of 18.9% of the patients with PD were classified as MCI, with a relative risk of 2.1 (1.2-3.6) in PD compared to the control group. Patients with PD with and without MCI did not differ significantly regarding demographic and motor features. Among PD-MCI patients, nearly two-thirds had a non-amnestic MCI subtype, and one third had an amnestic MCI subtype. CONCLUSIONS: The findings demonstrate a twofold increase in the proportion with cognitive impairment in subjects with early, untreated Parkinson disease (PD) compared to controls. This has implications for diagnosis and management of PD. AD = Alzheimer disease; aMCI-MD = amnestic multiple-domain MCI; aMCI-SD = amnestic single-domain MCI; CVLT-2 = California Verbal Learning Test II; IQCode = Informant Questionnaire on Cognitive decline in the elderly; MADRS = Montgomery and Aasberg Depression Rating Scale; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; naMCI-MD = non-amnestic multiple-domain MCI; naMCI-SD = non-amnestic single-domain MCI; PD = Parkinson disease; RR = relative risks; UPDRS = Unified Parkinson's Disease Rating Scale; VOSP = Visual Object and Space Perception Battery.

Neuropsychiatric symptoms in patients with Parkinson's disease and dementia: frequency, profile and associated care giver stress.

OBJECTIVE: To explore the profile of neuropsychiatric symptoms in patients with dementia associated with Parkinson's disease (PDD). METHODS: 537 patients with PDD drawn from an international multicentre clinical trial of rivastigmine were assessed using the 10-item Neuropsychiatric Inventory (NPI). A cluster analysis was used to investigate the inter-relationship of NPI items. Associations between the clusters and demographic and clinical variables were analysed. RESULTS: 89% of the patients presented at least one symptom on the NPI, 77% had two or more symptoms and 64% had at least one symptom with a score > or = 4. The most common symptoms were depression (58%), apathy (54%), anxiety (49%) and hallucinations (44%). Patients with more severe dementia and advanced Parkinson's disease had more neuropsychiatric symptoms. Nearly 60% of the care givers reported at least one NPI symptom to be of at least moderate severe distress. Five NPI clusters were identified: one group with few and mild symptoms (52%); a mood cluster (11%, high scores on depression, anxiety and apathy); apathy (24%; high apathy and low scores on other items); agitation (5%, high score on agitation and high total NPI score); and a psychosis cluster (8%; high scores on delusions and hallucinations). The psychosis and agitation clusters had the lowest Mini-Mental State Examination score and the highest Unified Parkinson's Disease Rating Scale and care giver distress scores. CONCLUSION: Neuropsychiatric symptoms are common in patients with PDD. The profile of these symptoms differs from that in other types of dementia. Subgroups with different neuropsychiatric profiles were identified. These subgroups may be associated with distinct neurobiological changes, which should be explored in future studies.

Attentional deficits affect activities of daily living in dementia-associated with Parkinson's disease.

OBJECTIVE: To investigate the effects of attentional deficits on activities of daily living (ADL) in patients with dementia associated with Parkinson's disease (PDD). METHOD: 461 patients were assessed neuropsychologically. Factor analyses were used to differentiate attention from other cognitive functions and to differentiate different aspects of ADL functions. The effects of the attentional measure on ADL were examined using sequential multiple regression, controlling for age, sex, education, severity of motor symptoms and other cognitive functions. RESULTS: Three cognitive factors were identified, with one factor emerging as a measure of vigilance and focused attention. This factor predicted different aspects of ADL status even after controlling for motor functions and other cognitive factors. The attention factor was the single strongest cognitive predictor of ADL status, matching the strength of the effects of motor functions on ADL status. CONCLUSION: Impaired attention is an important determinant of ADL functions in patients with PDD.

Neuropsychiatric disturbances in Parkinson's disease clusters in five groups with different prevalence of dementia.

OBJECTIVE: To investigate the inter-relationship of neuropsychiatric disturbances in Parkinson's disease (PD) by cluster analysis and describe the properties of the clusters. METHOD: A total of 139 patients were assessed using the neuropsychiatric inventory (NPI). A cluster-analysis was used to investigate the inter-relationship of NPI items. The clusters were profiled regarding dementia (PDD) and major depression. RESULTS: A total of 39 patients showed no neuropsychiatric symptoms. The remaining 100 patients (43% PDD) were divided in to five clusters. The largest group (42, 31% PDD) showed symptoms of mild depression, followed by a group (29, 79.3% PDD) with hallucinations and mild other symptoms. The third group (14, 7.1% PDD) had sleep disturbances exclusively. The fourth group (8, 25% PDD) showed apathy, anxiety and depression. The smallest group (7, 57.1% PDD) had high scores on several NPI items. CONCLUSION: Our PD sample can be divided in to clusters based on the NPI, with different prevalence of dementia and depression.

Effects of attention on dichotic listening: an 15O-PET study.

The present study investigated the effect of attention on brain activation in a dichotic listening situation. Dichotic listening is a technique to study laterality effects in the auditory sensory modality. Two different stimuli were presented simultaneously, one in each ear. Twelve subjects listened to lists of consonant-vowel syllables, or short musical instrument passages, with the task of detecting a "target" syllable or musical instrument by pressing a button. The target stimulus appeared an equal number of times in the left and right ear. The subjects were instructed to either concentrate on the stimuli presented in both ears, or only on the left or right ear stimulus. Brain activation was measured with 15O-PET, and significant changes in regional normalized counts (rNC) were evaluated using statistical parametric mapping (SPM96) software. Concentrating on either the right or left ear stimulus significantly decreased activity bilaterally in the temporal lobes compared to concentrating on both ear stimuli, at the expense of an increased activation in the right posterior and inferior superior parietal lobe. The CV-syllables activated areas corresponding to the classic language areas of Broca and Wernicke. The musical instrument stimuli mainly activated areas in visual association cortex, cerebellum, and the hippocampus. An interpretation of the findings is that attention has a facilitating effect for auditory processing, causing reduced activation in the primary auditory cortex when attention is explicitly recruited. The observed activations in the parietal lobe during the focused attention conditions could be part of a modality non-specific "attentional network".

Brain activation during dichotic presentations of consonant-vowel and musical instrument stimuli: a 15O-PET study.

Dichotic listening means that two different stimuli are presented at the same time, one in each ear. This technique is frequently used in experimental and clinical studies as a measure of hemispheric specialization. The primary aim of the present study was to record regional changes in the distribution of cerebral blood flow (CBF) with the 15O-PET technique to dichotically presented consonant-vowel (CV) and musical instrument stimuli, in order to test the basic assumption of differential hemispheric involvement when stimuli presented to one ear dominate over stimuli presented in the other ear. All stimuli were 380 ms in duration with a 1000 ms interstimulus interval, and were presented in blocks of either CV-syllable or musical instrument pairs. Twelve normal healthy subjects had to press a button whenever they detected a CV-syllable or a musical instrument target in a stream of CV- and musical instrument distractor stimuli. The targets appeared equally often in the right and left ear channel. The CV-syllable and musical instrument targets activated bilateral areas in the superior temporal gyri. However, there were significant interactions with regard to asymmetry of the magnitude of peak activation in the significant activation clusters. The CV-syllables resulted in greater neural activation in the left temporal lobe while the musical instruments resulted in greater neural activation in the right temporal lobe. Within-subjects correlations between magnitude of dichotic listening and CBF asymmetry were, however, non-significant. The changes in neural activation were closely mimicked by the performance data which showed a right ear superiority in response accuracy for the CV-syllables, and a left ear superiority for the musical instruments. In addition to the temporal lobe activations, there were activation tendencies in the left inferior frontal lobe, right dorsolateral prefrontal cortex, left occipital lobe, and cerebellum.

Event-related potentials (ERPs) to deviant auditory stimuli during sleep and waking.

Using an oddball paradigm with two tones differing in pitch and probability, event-related potentials (ERPs) were compared during wake and two sleep stages. REM and NREM sleep stages were identified in nine subjects using the Nightcap which continuously records eye and body movements. The N1 occurred later and the P2 was larger during sleep than when awake. The N1 to the infrequent tones was larger during both sleep stages. A late negative wave was significantly larger to infrequent tones during REM sleep. It is concluded that representations of auditory stimuli occur in sleep, and most prominently during the REM phase. The prolonged latency of the ERP components indicates that processing of external sensory stimuli may be delayed.