"Cerebellar Challenge" for Older Adults: Evaluation of a Home-Based Internet Intervention

There is converging evidence that maintenance of function in the multiple connectivity networks involving the cerebellum is a key requirement for healthy aging. The present study evaluated the effectiveness of a home-based, internet-administered “cerebellar challenge” intervention designed to create progressive challenges to vestibular function, multi-tasking, and dynamic coordination. Participants (n = 98, mean age 68.2, SD 6.6) were randomly allocated to either intervention (the cerebellar challenge training for 10 weeks) or no intervention. All participants undertook an initial series of pre-tests, and then an identical set of post-tests following the intervention period. The test battery comprised five suites of tests designed to evaluate cognitive-sensori-motor-affective functions, including Physical Coordination, Memory, Language Dexterity, Fluid Thinking and Affect. The intervention group showed significant pre- to post improvements in 9 of the 18 tests, whereas the controls improved significantly on one only. Furthermore, the intervention group showed significantly greater improvement than the controls on the “Physical Coordination” suite of tests, with evidence also of differential improvement on the Delayed Picture Recall test. Frequency of intervention use correlated significantly with the improvement in balance and in peg-moving speed. It is concluded that an internet-based cerebellar challenge programme for older adults can lead to benefits in balance, coordination and declarative memory. Limitations and directions for further research are outlined

Failure to Modulate Attentional Control in Advanced Aging Linked to White Matter Pathology

Advanced aging is associated with reduced attentional control and less flexible information processing. Here, the origins of these cognitive effects were explored using a functional magnetic resonance imaging task that systematically varied demands to shift attention and inhibit irrelevant information across task blocks. Prefrontal and parietal regions previously implicated in attentional control were recruited by the task and most so for the most demanding task configurations. A subset of older individuals did not modulate activity in frontal and parietal regions in response to changing task requirements. Older adults who did not dynamically modulate activity underperformed their peers and scored more poorly on neuropsychological measures of executive function and speed of processing. Examining 2 markers of preclinical pathology in older adults revealed that white matter hyperintensities (WMHs), but not high amyloid burden, were associated with failure to modulate activity in response to changing task demands. In contrast, high amyloid burden was associated with alterations in default network activity. These results suggest failure to modulate frontal and parietal activity reflects a disruptive process in advanced aging associated with specific neuropathologic processes

PET studies of the dopamine system in relation to cognitive functions

The human brain is intricately designed to execute cognitive functions such as perception, attention, memory and learning. Deficits in cognitive functions accompany major psychiatric disorders such as schizophrenia, attention deficit hyperactivity disorder and Parkinson s disease. The biological underpinnings of cognitive functions, is however poorly understood. One of the neurotransmitters proposed to play a central role in cognition is dopamine (DA). Positron emission tomography (PET) is a non-invasive molecular imaging technique by which biomarkers for neurotransmission systems can be examined in the human brain in vivo and related to higher brain functions. Development of new tests based on advances in cognitive science provides tools to identify basic elements of cognition. The first aim of the present thesis was to develop improved methodologies, both for molecular imaging and cognitive testing. The second aim was to apply these methods in a combined fashion with the intention to increase understanding of the organization of the DA system in the human brain and its role in cognitive functions. In the first study, a new selective radioligand for the dopamine transporter (DAT) was developed. [11C]PE2I binding was characterized in four non-human primates and in one human control subject, showing better selectivity for the DAT when compared to previously developed radioligands. In addition, the distinctive contrast of this radioligand demonstrated sufficient signal not only in striatum, but also in substantia nigra. The relationship between the presynaptic DAT and the mainly postsynaptic DA D2 receptor was examined in a double-tracer PET study (Study II). The results from 17 human subjects demonstrated a lack of a correlation, suggesting independent regulation of the two DA biomarkers in the human striatum. The results suggest that these two biomarkers may not be mutually interchangeable when assessing the DAergic system in the healthy brain. Visuospatial working memory (VSWM) is commonly impaired in patients with schizophrenia resulting in disorganization in both thoughts and behavior. In Study III, a standard VSWM-test was modified to reduce ceiling effects among control subjects, thus allowing for a less biased comparison between patients with schizophrenia and controls. In addition, during high WM load the control group showed improved performance when the stimulus arrangement invited the use of cognitive strategies, as compared to an arrangement with random location of the target stimulus. This improvement was not present in the patient group. The results indicate that patients with schizophrenia do not make use of, or generate strategies to the same extent as control subjects. In the final study, the role of the DAT was examined in relation to cognitive aging. Cognitive performance was assessed in 12 human subjects, ranging from 34-81 years of age, and DAT density was quantified using PET. The results indicate that DAT may serve as a biomarker of age-related deficits in episodic memory and executive function, and that DAT is implicated in cognitive performance irrespective of age. In conclusion the present thesis, based on a combination of molecular imaging and cognitive assessment, corroborates a role for the DA system in higher brain functions in man

Improved cognitive functions after treatment with an oral appliance in obstructive sleep apnea

Åke Tegelberg,1,4,5 Bo Wilhelmsson,2 Nina Erixon-Lindroth,6 Leif H Lindström3,41Department of Stomatognathic Physiology, 2Department of Otorhinolaryngology, 3Department of Psychiatry, Central Hospital, Västerås, Sweden; 4Centre for Clinical Research, Uppsala University, Central Hospital, Västerås, Sweden; 5Faculty of Odontology, Malmö University, Malmö, Sweden; 6Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, SwedenObjective: The objective of this study was to evaluate the effect of oral appliance (OA) treatment on cognitive functions in patients with obstructive sleep apnea (OSA).Materials and methods: In a prospective study, 50 male patients with verified moderate-to-severe OSA received an OA with mandibular advancement. The cognitive functions assessed included working memory, vigilance, executive functioning, and mental pace, measured before as well as after 6 months of treatment. Somnography was used to measure physiological treatment effects. Forty-three patients completed the 6-month follow-up study.Results: All domains of cognitive functioning measured improved after 6 months of treatment with an OA (P < 0.001). The apnea/hypopnea- and oxygen desaturation-indices decreased significantly after treatment (P < 0.01). An obvious treatment response was reached in 60% of the patients, and 54% of the patients had recovered ie, had normalized breathing during sleep.Conclusion: OA with mandibular advancement is a treatment modality for the physiological symptoms of OSA, and may have a positive impact on cognitive functions, after only 6 months of treatment.Keywords: clinical trial, cognition, oral appliance, sleep apnea, treatmen

Improved cognitive functions after treatment with an oral appliance in obstructive sleep apnea

OBJECTIVE: The objective of this study was to evaluate the effect of oral appliance (OA) treatment on cognitive functions in patients with obstructive sleep apnea (OSA). MATERIALS AND METHODS: In a prospective study, 50 male patients with verified moderate-to-severe OSA received an OA with mandibular advancement. The cognitive functions assessed included working memory, vigilance, executive functioning, and mental pace, measured before as well as after 6 months of treatment. Somnography was used to measure physiological treatment effects. Forty-three patients completed the 6-month follow-up study. RESULTS: All domains of cognitive functioning measured improved after 6 months of treatment with an OA (P <; 0.001). The apnea/hypopnea- and oxygen desaturation-indices decreased significantly after treatment (P <; 0.01). An obvious treatment response was reached in 60% of the patients, and 54% of the patients had recovered ie, had normalized breathing during sleep. CONCLUSION: OA with mandibular advancement is a treatment modality for the physiological symptoms of OSA, and may have a positive impact on cognitive functions, after only 6 months of treatment