Profiles of subjective health among people living alone: a latent class analysis.

BACKGROUND: Living alone has increased globally and especially in Finland where 45% of all households are single occupancy. Epidemiological research has found that living alone a risk factor for a wide range of adversities related to quality of life but the rapidly-changing demographics of people living alone calls for a more detailed investigation of their subjective health status. METHODS: Using a cross-sectional survey sent for a random sample of Finnish residents in single-person households (n = 884), we explored with latent class analysis whether the respondents form different health profiles based on the three health dimensions defined by the World Health Organization: physical, social, and mental well-being. The identified groups were then compared in terms of demographic characteristics with the χ2 test and quality of life using linear regression models. Sensitivity analyses were run using more refined, manual 3-step BCH method. RESULTS: Four distinct health profiles were found: Languishing (4%), Managing (35%), Healthy (30%), and Flourishing (31%). The groups differed in most socio-demographic aspects such as marital and employment status, but not in terms of geographic location or gender (apart from group Languishing that contained more men). Controlling for these socio-demographic differences, all groups showed different average levels of perceived quality of life to the expected direction. CONCLUSIONS: Our findings suggest that people living alone are indeed a very heterogeneous group in terms of subjective health. Instead of seeing living alone as a mere risk for low quality of life, concept of living alone should be understood more broadly both in public discussion and scientific research.

Biallelic Mutations in PDE10A Lead to Loss of Striatal PDE10A and a Hyperkinetic Movement Disorder with Onset in Infancy.

Deficits in the basal ganglia pathways modulating cortical motor activity underlie both Parkinson disease (PD) and Huntington disease (HD). Phosphodiesterase 10A (PDE10A) is enriched in the striatum, and animal data suggest that it is a key regulator of this circuitry. Here, we report on germline PDE10A mutations in eight individuals from two families affected by a hyperkinetic movement disorder due to homozygous mutations c.320A>G (p.Tyr107Cys) and c.346G>C (p.Ala116Pro). Both mutations lead to a reduction in PDE10A levels in recombinant cellular systems, and critically, positron-emission-tomography (PET) studies with a specific PDE10A ligand confirmed that the p.Tyr107Cys variant also reduced striatal PDE10A levels in one of the affected individuals. A knock-in mouse model carrying the homologous p.Tyr97Cys variant had decreased striatal PDE10A and also displayed motor abnormalities. Striatal preparations from this animal had an impaired capacity to degrade cyclic adenosine monophosphate (cAMP) and a blunted pharmacological response to PDE10A inhibitors. These observations highlight the critical role of PDE10A in motor control across species.

Use of Health Services Among People Living Alone in Finland.

Although health issues are more common in people living alone than in those living with someone, research on the service use of people living alone has focused on older age groups. Based on large Finnish cross-sectional health survey (FinHealth 2017, n = 4686), we examined the difference in the use and assessment of health services between those living alone and those living with someone, and whether some sub-groups within those living alone use or perceive the use of health care services differently to those living with someone. The adjusted proportions, based on logistic regression models controlling for demographic variables and perceived health and mental health, showed that those living alone had seen a doctor in the past year less often (65.5%) than those not living alone (71.9%). People living alone had also less often had a health examination in the past 5 years (72.4%) than those not living alone (79.2%), and this proportion was particularly low within people living alone with high levels of depressive symptoms (59.0%) compared to lower levels (75.0%). Conclusively, among people living alone, those who suffer from depressive symptoms might be a potential group that does not receive the same levels of preventive care than others.

Reading, listening and memory-related brain activity in children with early-stage temporal lobe epilepsy of unknown cause-an fMRI study.

BACKGROUND AND AIMS: The changes in functional brain organization associated with paediatric epilepsy are largely unknown. Since children with epilepsy are at risk of developing learning difficulties even before or shortly after the onset of epilepsy, we assessed the functional organization of memory and language in paediatric patients with temporal lobe epilepsy (TLE) at an early stage in epilepsy. METHODS: Functional magnetic resonance imaging was used to measure the blood oxygenation level-dependent (BOLD) response to four cognitive tasks measuring reading, story listening, memory encoding and retrieval in a population-based group of children with TLE of unknown cause (n = 21) and of normal intelligence and a healthy age and gender-matched control group (n = 21). RESULTS: Significant BOLD response differences were found only in one of the four tasks. In the story listening task, significant differences were found in the right hemispheric temporal structures, thalamus and basal ganglia. Both activation and deactivation differed significantly between the groups, activation being increased and deactivation decreased in the TLE group. Furthermore, the patients with abnormal electroencephalograms (EEGs) showed significantly increased activation bilaterally in the temporal structures, basal ganglia and thalamus relative to those with normal EEGs. The patients with normal interictal EEGs had a significantly stronger deactivation than those with abnormal EEGs or the controls, the differences being located outside the temporal structures. CONCLUSIONS: Our results suggest that TLE entails a widespread disruption of brain networks. This needs to be taken into consideration when evaluating learning abilities in patients with TLE. The thalamus seems to play an active role in TLE. The changes in deactivation may reflect neuronal inhibition.

Neuropsychological performance in children with temporal lobe epilepsy having normal MRI findings.

BACKGROUND AND AIMS: Most information on the neuropsychological performance of pediatric patients with temporal lobe epilepsy (TLE) is derived from selected surgical series. Non-lesional pediatric TLE patients were studied here at the population level in order to investigate the extent to which neuropsychological deficits predisposing to learning difficulties exist in this more common group. METHODS: Language, memory and executive functions were measured in children aged 8-15 years with non-lesional TLE and of normal intelligence (n = 21), and their performance was compared with that of healthy age and gender-matched children (n = 21). The effects of clinical epilepsy variables on performance were examined. RESULTS: Although neuropsychological performance did not differ between the TLE patients and the healthy controls, female gender, early onset, longer duration and abnormal interictal EEG had a negative effect on neuropsychological performance. CONCLUSIONS: Children with early-onset epilepsy should be assessed carefully for neuropsychological impairment using sufficiently broad batteries of tests in order to detect even slight deficits. Our sample size was small and these findings should be interpreted as preliminary results and need to be confirmed in larger studies.

A multicenter study on Leigh syndrome: disease course and predictors of survival.

BACKGROUND: Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients. METHODS: This is a retrospective study of patients with Leigh syndrome that have been followed at eight centers specialising in mitochondrial diseases in Europe; Gothenburg, Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu. RESULTS: A total of 130 patients were included (78 males; 52 females), of whom 77 patients had identified pathogenic mutations. The median age of disease onset was 7 months, with 80.8% of patients presenting by the age of 2 years. The most common clinical features were abnormal motor findings, followed by abnormal ocular findings. Epileptic seizures were reported in 40% of patients. Approximately 44% of patients experienced acute exacerbations requiring hospitalisation during the previous year, mainly due to infections. The presence of pathological signs at birth and a history of epileptic seizures were associated with higher occurrence of acute exacerbations and/or relapses. Increased lactate in the cerebrospinal fluid was significantly correlated to a more severe disease course, characterised by early onset before 6 months of age, acute exacerbations and/or relapses, as well as brainstem involvement. 39% of patients had died by the age of 21 years, at a median age of 2.4 years. Disease onset before 6 months of age, failure to thrive, brainstem lesions on neuroimaging and intensive care treatment were significantly associated with poorer survival. CONCLUSIONS: This is a multicenter study performed in a large cohort of patients with Leigh syndrome. Our data help define the natural history of Leigh syndrome and identify novel predictors of disease severity and long-term prognosis.

Connectivity disruptions in resting-state functional brain networks in children with temporal lobe epilepsy.

Functional resting-state connectivity has been shown to be altered in certain adult epilepsy populations, but few connectivity studies have been performed on pediatric epilepsy patients. Here functional connectivity was measured in pediatric, non-lesional temporal lobe epilepsy patients with normal intelligence and compared with that in age and gender-matched healthy controls using the independent component analysis method. We hypothesized that children with non-lesional temporal lobe epilepsy have disrupted functional connectivity within resting-state networks. Significant differences were demonstrated between the two groups, pointing to a decrease in connectivity. When the results were analyzed according to the interictal electroencephalogram findings, however, the connectivity disruptions were seen in different networks. In addition, increased connectivity and abnormally anti-correlated thalamic activity was detected only in the patients with abnormal electroencephalograms. In summary, connectivity disruptions are already to be seen at an early stage of epilepsy, and epileptiform activity seems to affect connectivity differently. The results indicate that interictal epileptiform activity may lead to reorganization of the resting-state brain networks, but further studies would be needed in order to understand the pathophysiology behind this phenomenon.

Alterations in regional homogeneity of baseline brain activity in pediatric temporal lobe epilepsy.

Recent findings on intracortical EEG measurements show that the synchrony of localized neuronal networks is altered in epileptogenesis, leading to generalized seizure activity via connector hubs in the neuronal networks. Regional homogeneity (ReHo) analysis of blood oxygen level-dependent (BOLD) signals has demonstrated localized signal synchrony and disease-related alterations in a number of instances. We wanted to find out whether the ReHo of resting-state activity can be used to detect regional signal synchrony alterations in children with non-lesional temporal lobe epilepsy (TLE). Twenty-one TLE patients were compared with age and gender-matched healthy controls. Significantly increased ReHo was discovered in the posterior cingulate gyrus and the right medial temporal lobe of the patients, and they also had significantly decreased ReHo in the cerebellum compared with the healthy controls. However, the alterations in ReHo differed between the patients with normal and abnormal interictal EEGs, the latter showing significantly increased ReHo in the right fusiform gyrus and significantly decreased ReHo in the right medial frontal gyrus relative to the controls, while those with normal EEGs had significantly increased ReHo in the right inferior temporal gyrus and the left posterior cingulate gyrus. We conclude that altered BOLD signal synchrony can be detected in the cerebral and cerebellar cortices of children with TLE even in the absence of interictal EEG abnormalities.

Age-Related Differences in Functional Nodes of the Brain Cortex - A High Model Order Group ICA Study.

Functional MRI measured with blood oxygen dependent (BOLD) contrast in the absence of intermittent tasks reflects spontaneous activity of so-called resting state networks (RSN) of the brain. Group level independent component analysis (ICA) of BOLD data can separate the human brain cortex into 42 independent RSNs. In this study we evaluated age-related effects from primary motor and sensory, and, higher level control RSNs. One hundred sixty-eight healthy subjects were scanned and divided into three groups: 55 adolescents (ADO, 13.2 ± 2.4 years), 59 young adults (YA, 22.2 ± 0.6 years), and 54 older adults (OA, 42.7 ± 0.5 years), all with normal IQ. High model order group probabilistic ICA components (70) were calculated and dual-regression analysis was used to compare 21 RSN's spatial differences between groups. The power spectra were derived from individual ICA mixing matrix time series of the group analyses for frequency domain analysis. We show that primary sensory and motor networks tend to alter more in younger age groups, whereas associative and higher level cognitive networks consolidate and re-arrange until older adulthood. The change has a common trend: both spatial extent and the low frequency power of the RSN's reduce with increasing age. We interpret these result as a sign of normal pruning via focusing of activity to less distributed local hubs.