Forskningsartikler

Preprint

Abstract:

Mental and neurological conditions have been linked to structural brain variations. However, aside from dementia, the value of brain structural characteristics derived from brain scans for prediction is relatively low. One reason for this limitation is the clinical and biological heterogeneity inherent to such conditions. Recent studies have implicated aberrations in the cerebellum, a relatively understudied brain region, in these clinical conditions. Here, we used machine learning to test the value of individual deviations from normative cerebellar development across the lifespan (based on trained data from >27k participants) for prediction of autism spectrum disorder (ASD) (n=317), bipolar disorder (BD) (n=238), schizophrenia (SZ) (n=195), mild cognitive impairment (MCI) (n=122), and Alzheimer’s disease (AD) (n=116). We applied several atlases and derived median, variance, and percentages of extreme deviations within each region of interest. Our results show that lobular and voxel-wise cerebellar data can be used to discriminate healthy controls from ASD and SZ with moderate accuracy (the area under the receiver operating characteristic curves ranged from 0.56 to 0.64), The strongest contributions to these predictive models were from posterior regions of the cerebellum, which are more strongly linked to higher cognitive functions than to motor control.

Milin Kim, Nitin Sharma, Esten H. Leonardsen, Saige Rutherford, Geir Selbæk, Karin Persson, Nils Eiel Steen, Olav B. Smeland, Torill Ueland, Geneviève Richard, Aikaterina Manoli, Sofie L. Valk, Dag Alnæs, Christian F. Beckman, Andre F. Marquand, Ole A. Andreassen, Lars T. Westlye, Thomas Wolfers, Torgeir Moberget

Background/Objectives: The annual incidence of falls is high in older adults with impaired cognitive function and dementia, and injuries have a detrimental effect on disability-adjusted life-years and public health spending. In this registry-based study, fall incidence and characteristics of the fallers were explored in a large population with cognitive impairment.
Methods: NorCog, “The Norwegian Registry of Persons Assessed for Cognitive Symptoms”, is a national research and quality registry with a biomaterial collection. This study included 9525 persons from the registry who had answered the question about falls. Fall incidence was studied, and the characteristics of fallers and non-fallers were compared.
Results: The annual fall incidence was 3774/9525 (39.6%). The incidence varied between types of dementia, from 22.4% in persons with the debut of Alzheimer’s disease before 65 years of age to 55.3% in persons with vascular dementia and with increasing degrees of cognitive impairment. A wide range of personal characteristics, symptoms, signs, laboratory tests, and physical, psychological, and cognitive tests differed between fallers and non-fallers, most in disfavour of the fallers. Age, reduced Personal Activities of Daily Living, reduced gait speed, delayed recall, use of a walking aid, and depression were independent predictors of falls.
Conclusions: Among cognitively impaired persons with a history of falls, frailty was an independent predictor of falls. Neither the type of dementia nor the degree of cognitive impairment were independent predictors of falls. Prevention of frailty by physical training and social activity may be important in mitigating fall risk among older adults with impaired cognition.

Per G. Farup, Knut Hestad and Knut Engedal

Abstract

Objectives: Dementia significantly impacts quality of life, health care costs, and caregiver burden, being a leading cause of death among older adults. We investigated predictors of mortality in people with severe behavioral and psychological symptoms of dementia (BPSD).

Design: A multicentric longitudinal observational study was conducted, comprising clinical assessments at baseline and every 6 months for 3 years.

Setting and participants: People with severe BPSD (Neuropsychiatric Inventory, NPI ≥32) living at home.

Methods: Data on demographics and clinical characteristics were collected at baseline and during 6-monthly follow-ups over 3 years. The main outcome was mortality, documented over a total period of 4 years and analyzed using the Cox proportional hazards model.

Results: Of the 508 patients with dementia with severe BPSD, 165 (32.5%) died during the 4-year follow-up. Non-survivors were older (79.8 ± 7.7 vs 77.3 ± 8.0; P < .001), more likely to be male (58.8% vs 38.5%; P < .001), and had higher BPSD severity (NPI: 57.2 ± 20.2 vs 50.3 ± 17.9; P < .001), lower cognitive function according to the Mini-Mental State Examination (MMSE) (13.5 ± 6.6 vs 16.4 ± 5.9; P < .001), and worse functional status according to the Alzheimer’s Disease Cooperative Study – Activities of Daily Living Scale (ADCS) (28.8 ± 16.4 vs 36.3 ± 17.2; P < .001) at baseline. Significant predictors of mortality included male sex (hazard ratio [HR], 2.03; 95% confidence interval [95% CI], 1.46-2.82; P < .001), older age at diagnosis (HR, 1.05; 95% CI, 1.03-1.07; P < .001), higher NPI scores (HR, 1.01; 95% CI, 1.01-1.02; P = .002), lower MMSE (HR, 0.95; 95% CI, 0.93-0.98; P = .001), lower ADCS (HR, 0.98; 95% CI, 0.98-0.99; P = .015), and lower quality of life rated by proxy (HR, 0.97; 95% CI, 0.95-0.99; P = .021). The use of antidepressants (HR, 0.69; 95% CI, 0.48-0.98; P = .038) was associated with increased survival. Delusions (HR, 1.0; 95% CI, 1.03-1.12; P < .001), hallucinations (HR, 1.07; 95% CI, 1.02-1.11; P = .002), and agitation/aggression (HR, 1.05; 95% CI, 1.01-1.09; P = .021) were significantly linked to increased mortality.

Conclusions and implications: Older age, male sex, severe BPSD, and lower cognitive and quality of life scores significantly predict increased mortality in patients with severe BPSD.

Aline Mendes, François R Herrmann, Sverre Bergh, Bruno Mario Cesana, Ron Handels, Alfonso Ciccone, Emmanuel Cognat, Andrea Fabbo, Sara Fascendini, Giovanni B Frisoni, Lutz Froelich, Maria Cristina Jori, Patrizia Mecocci, Paola Merlo, Oliver Peters, Magdalini Tsolaki, Carlo Alberto Defanti