S7.4 Biomarkers and clinical factors in mild cognitive impairment and dementia – a multicenter study
Chair: Maria Barca
To predict progression of cognitive decline in patients with mild cognitive impairment (MCI) and dementia. The Prognosis of Alzheimer’s disease and resourse use (PADR) cohort consists of 555 patients from three memory clinics. At baseline, a comprehensive assessment was performed including clinical history, neuropsychological, neuropsychiatric (depression) and medical examination, MRI, blood sample for blood chemistry and examination of inflammatory markers, ApoE status and examination of spinal fluid for a subgroup. At baseline, 105 patients had amnestic MCI according to Winblad’s criteria and memory tests and 177 had Alzheimer disease (AD) dementia according to the NINCDS-ADRDA. These patients were followed up after mean of 24 months (range 16-36) after baseline with the same battery as at baseline. Additionally, saliva samples for cortisol were collected at follow-up. This proposed symposium will report on the progression of MCI and AD and examine whether depression, vascular factors, exposure to inappropriate drugs, ApoE genotype, MRI findings, inflammatory markers, stress or CSF markers predicts progression as measured by change in Clinical Dementia Rating scale sum of boxes. Additional results comparing data from the PADR study on stress with elderly from Old Age Psychiatry wards and from the community will be presented. Results will be presented at the symposium in five presentations.
S7.4.1 Do vascular risk factors and vascular diseases influence disease progression in Alzheimer’s disease?
Rannveig S. Eldholm1, Karin Persson2, Maria Lage Barca2, Geir Selbæk2, Knut Engedal2 and Ingvild Saltvedt1
1Norwegian University of Science and Technology, Norway, 2National Advisory Unit for Ageing and Health, Norway
Background: Vascular risk factors increase the risk of developing Alzheimer’s disease (AD). There is limited evidence on the impact of vascular diseases and risk factors on disease progression after symptom onset. The aim was to examine the association between vascular disease and vascular risk factors and progression of AD. Methods: Vascular burden was estimated by the Framingham Stroke Risk Profile (FSRP). The associations between vascular conditions and change in CDR-SB scores were analysed by multiple regression analyses, adjusted for age and sex. Results: In total, 282 patients diagnosed with AD dementia or amnestic MCI were included. Hypertension was shown in 83%, hypercholesterolemia 53%, overweight 38%, diabetes 9%, and 10% were smokers. One third had a history of vascular disease; 16% heart disease and 15% cerebrovascular events. Progression rates in AD show considerable variation, and almost half of the patients in the PADR study showed little or no progression during follow-up. None of the vascular risk factors or diseases nor the FSRP score was associated with disease progression. Conclusion: The results suggest substantial heterogeneity in disease progression. Vascular risk factors and vascular diseases do not influence the cognitive decline in memory clinic patients with MCI or mild to moderate dementia.
S7.4.2 Depressive symptoms and their relationship to the progression of dementia and cortisol levels?
Maria Lage Barca1, Rannveig S. Eldholm2, Karin Persson1, Guro Hanevold Bjørkløf1, Tom Borza5, Elisabeth Telenius4, Anne-Brita Knapskog3, Anne Brækhus3, Ingvild Saltvedt2, Geir Selbæk1 and Knut Engedal1
1National Advisory Unit for Ageing and Health, Norway, 2 Norwegian University of Science and Technology, Norway, 3 Oslo University Hospital, Ullevål, Norway; 4Oslo Metropolitan University – OsloMet, Norway, 5Sykehus Innlandet, Norway
Background: Increasing depressive symptoms are associated with faster progression of dementia in the PADR study. Depression and dementia may lead to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. We wanted to investigate if patients with both depression and dementia have higher level of cortisol compared to patients with depression without dementia, dementia without depression and older persons without depression or dementia. Methods: A sample of 650 old people (dementia n=319, depression, n=154, dementia + depression n=53, controls n=124) living at home and in nursing home was included. Assessment included MMSE, Cornell, ADL scales and salivary cortisol, three times at the same day. Cortisol levels were compared across the four groups. Multivariate linear regression analyses were performed to investigate associations to cortisol levels. Results: Patients with depression and dementia had higher levels of evening cortisol (p=0.033) and cortisol ratio (p=0.044) compared to controls, but lower levels than patients with dementia without depression (p=0.020 and p=0.003, respectively) and higher cortisol ratio (p=0.003) than non-demented patients with depression. Associates of cortisol levels will be presented. Conclusion: Levels of cortisol are higher among patients with depression and dementia than old people without depression and dementia and patients with depression, but lower than patients with dementia.
S7.4.3 MRI assessed atrophy subtypes in Alzheimer’s disease with mild degree of dementia
Karin Persson1, Maria Lage Barca1, Rannveig Sakshaug Eldholm2, Anne-Brita Knapskog3, Maria Vistnes4, Lena Cavallin, Daniel Ferreira, Geir Selbæk1, Anne Brækhus3, Ingvild Saltvedt2, Eric Westman, Knut Engedal1
1National Advisory Unit for Ageing and Health, Norway, 2 Norwegian University of Science and Technology, Norway, 3 Oslo University Hospital, Ullevål, Norway; 4University of Oslo, Norway
Background: Four patterns of MRI assessed brain atrophy have been demonstrated in patients with Alzheimer’s disease (AD) dementia: typical, limbic-predominant, hippocampal-sparing, and minimal-atrophy. These subtypes were also identified in the PADR study with similar prevalence as in previous studies. The aim was to compare demographic, clinical, progression rate, and biomarker data, including inflammatory markers and cortisol, between the subgroups, with a special emphasis on the subtype with minimal atrophy. Methods: In total, 123 patients diagnosed with mild AD dementia according to the ICD-10 and NINCDS-ADRDA criteria, and the clinical dementia rating scale (CDR) were included. Visual rating scales of medial temporal, frontal, and posterior brain regions were used with age-adjusted cut-offs to subtype the patients. ANOVA, t-tests and chi-square tests were carried out to compare the groups. Results: Lower level of education, a lower CDR-SB at baseline and higher level of beta-amyloid were found in the minimal-atrophy group compared to the other groups. No differences were found with regard to progression rate. The results regarding inflammatory markers and cortisol will be presented during the symposium. Conclusion: The discovery of an AD dementia subtype with minimal atrophy is of interest as one of the hallmarks of AD, i.e. atrophy, is less pronounced.
S7.4.4 Importance of low-grade inflammation in patients with cognitive impairment due to Alzheimer’s disease
Anne-Brita Knapskog1, Rannveig Eldholm2, Maria L. Barca3, Karin Persson3, Maria Vistnes4, Ingvild Saltvedt2, Geir Selbæk3 and Knut Engedal3
1Oslo University Hospital, Ullevål, Norway, 2Norwegian University of Science and Technology, Norway, 3National Advisory Unit for Ageing and Health, Norway, 4University of Oslo, Norway
Background: Neuroinflammation may play an important role in the pathogenesis of Alzheimer’s disease (AD). We wanted to examine if inflammatory activity at baseline could predict cognitive and functional decline among patients with mild cognitive impairment (MCI) and AD after 2 years, and if the levels of inflammatory activity remained stable during 2-year follow-up. We also wanted to explore the relationship between inflammatory activity and dementia stages. Methods: Samples of serum were collected from 250 patients with MCI and AD at baseline and 197 patients at follow-up after approximately two years (18 – 36 months), and analyzed for 14 inflammatory markers (interleukin (IL)-1?, -1ra, -6, -10, -12p40, -17a, -18, -22, -33, tumor necrosis factor (TNF), CD40 ligand, interferon (IFN)-?, CCL2 and -4) by bead-based multiplex immunoassay. Disease progression was measured by the annual increase in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) and annual decrease in the Mini-Mental State Examination test. Results: The samples are being analyzed, and the results will be presented at the congress. Conclusion: The results will contribute to a better understanding of the mechanisms behind AD.
S7.4.5 Inappropriate medications associated to cognitive decline in home-dwelling people with mild cognitive impairment and dementia
Hege Kersten1, Rannveig Sakshaug Eldholm2, Maria Lage Barca1, Karin Persson1, Ingvild Saltvedt2, Geir Selbæk1, Knut Engedal1
1National Advisory Unit for Ageing and Health, Norway, 2Norwegian University of Science and Technology, Norway
Background: Histamine-2 receptor antagonists, benzodiazepines and anticholinergic drugs are defined as inappropriate medications in older people with cognitive disorders (PIMcogs). This study investigated the association between PIMcog use and cognitive decline in patients with mild cognitive impairment (MCI) and dementia attending Norwegian memory clinics. Methods: Regularly prescribed drugs were recorded in the PADR-cohort, n=357, at baseline and follow-up and the prevalence of PIMcog was assessed at both visits. The association between PIMcog use and cognitive decline was evaluated. Results: The mean number of drugs used at baseline 3.39 (SD=2.73) increased to 4.47 (SD=3.31) at follow-up (p<0.001). At baseline 77 patients used 1-3 PIMcogs while at follow-up 105 patients used 1-5 PIMcogs, p<0.001. The highest increment was seen for benzodiazepines; 23 BZD-users at baseline and 46 BZD-users at follow up, p<0.001. Preliminary analyses did not identify any association between PIMcog use and cognitive decline. Conclusion: Even though the mean number of drugs was below five at both assessments, the prevalence of potentially exacerbating drugs increased from 21.5 % to 30 % after 24 months. However, PIMcog use was not associated with faster cognitive decline in preliminary results.