Analyse av søvnforstyrrelser, med fokus på REM søvn atferdsfortyrrelser, samt korrelasjoner med kognisjon og nevropatologisk diagnose.

Background: Sleep disorders are frequent in patients with dementia. Sleep disturbances can negatively influence the disease burden of dementia and accelerate the rate of cognitive decline. It is hypothesized that sleep pathology, such as REM sleep behavior disorder (RBD), can occur many years before symptomatic disease and that it can be one of the early manifestation of neurodegeneration in alpha-synucleinopathies, such as dementia with Lewy bodies (DLB). DLB is the third most frequent type of dementia, after Alzheimer’s dementia (AD) and vascular dementia (VaD). However, there are few validation studies of the DLB consensus criteria from 2005, and the criteria appear to still have low sensitivity. Objectives: The main goals of this thesis were: 1) to investigate the frequency of sleep disturbances in dementia and compare sleep disturbance profiles in a group of patients with AD and DLB; 2) to assess the potential influence of probable RBD (pRBD) on the rate of dementia progression; and 3) to compare neuropathological diagnoses with clinical diagnoses based on DLB ​​consensus criteria from 2005. Results: A total of 266 patients were included in the DEMVEST study, and our cohort consisted of 139 with AD, 82 with DLB, 17 with PDD, 13 with VaD and 5 with FTD, six with other diagnoses (normal ageing, mixed AD and VaD, alcoholic dementia, unspecified dementia). Numbers of participants varied in the three papers according to purposes of the studies. Paper 1: 56% of patients with dementia, represented by AD and DLB, had at least one sleep disorder, with predominance of insomni (34.8%). Sleep problems were significantly more frequent in the group of patients with DLB than with AD (73.2% vs. 45.7%, p<0,001). DLB diagnoses also increased the risk of having three or more sleep disorders. Having at least one sleep-related problem was associated with significantly higher rates of psychopathological symptoms compared to patients without any sleep disorders. The second most common sleep problem in the DLB group after insomni was pRBD, which was present in 40% of patients. Paper 2: Of the total 246 patients included at baseline we identified 47 (19.1%) with pRBD. Patients with pRBD had the same progression rate of dementia as patients without RBD, both in global cognition measured by MMSE and in different cognitive domains, during 4 years of follow-up. However, the results showed that patients with RBD had significantly lower performance in figure copying in MMSE, VOSP Cube, TMT A and Stroop Words compared to RBD-negative patients throughout the observation period. Paper 3: In a cohort of 56 patients who came to autopsy we found 31 cases with neuropathologically verified AD, 20 with DLB and PDD and five with other diagnoses. Results showed that for overall DLB/ PDD diagnosis there was a relative good consistency between the clinical and pathological diagnoses, with a sensitivity (SN) and specificity (SP) of 80% and 92% and that the positive predictive value (PPV) and negative predictive value (NPV) were 84% and 89% respectively. For possible and probable DLB alone (without PDD), the values ​​of 73% (SN), 93% (SP), 79% (PPV) and 90% (NPV) were found. Of the 56 patients, seven were misdiagnosed; three patients with false positive DLB diagnosis and four with false negative DLB diagnosis. Conclusions: Sleep disturbances are common in dementia, but patients with DLB have more sleep problems and a more complicated pattern of sleep pathology than those with AD. Occurrence of at least one sleep disturbance seems to be related to a more severe course of psychiatric symptoms. We could not demonstrate that pRBD is a risk factor for faster progression of global cognition and cognition in various cognitive domains of dementia. Sensitivity, specificity and accuracy of clinical diagnoses were similar to results from previous studies which applied DLB consensus criteria from 2005 and showed that there is still a need to improve sensitivity. The defense is scheduled for January 2019. The project underscores the need for better recognition and treatment of sleep disorders in people with dementia. The project also draws attention to the importance of RBD in the diagnosis of dementia with Lewy bodies, and the potential role of RBD in the early diagnosis of this type of dementia in preclinical stages. In the end, the project pays attention to the need for intensive studies to improve the accuracy and earlier identification of patients with the probable diagnosis of DLB. The last part of our project, neuropathological validation, is the starting point for the next validation of the new criteria from 2017.