Forskningsartikler

The aim of this study was to investigate whether cognitive performance was equally influenced by Apolipoprotein E (APOE, with its three alleles, e2, e3, and e4) in patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). In addition, we examined a group of patients with a combination of Vascular dementia (VaD) and AD (VaD/AD). We asked if the APOE e4 allele influenced cognition in these patient groups in the same way. Our study comprised data from 1,991 patients (55% women), with a mean age of 70.9 years (SD 10.8) and 12.1 years of education (SD 3.8). Of them, 1,111 (56%) had at least one APOE e4 allele; 871 (44%) had one and 240 (12%) had two e4 alleles. Three neurocognitive tests were used to measure cognition: the Mini Mental State Examination (MMSE), the 10-word test of the Consortium to Establish a Registry for Alzheimer’s Disease Word List (CERAD-WL) (immediate and delayed recall), and the Trail Making Test Part A (TMTA). The APOE genotypes were regressed against cognitive function using linear regression, adjusting for diagnosis, age, sex, and education. The interaction diagnosis∗APOE was investigated. The allele type had the largest effect on cognitive performance assessed by the CERAD-WL delayed recall test, less for the other tests. Those without the e4 type scored 0.7 units better than those with e4 allele(s) (p < 0.001). Furthermore, there was a significant inverse dose-response pattern between number of e4 alleles and cognitive performance; those with one allele scored 0.4 units better than those with two alleles (p = 0.006), and those without e4 scored 0.7 units better than those with one e4 (p < 0.001). This pattern did not differ between the four diagnostic groups studied.

Knut Hestad, Knut Engedal, Peter Horndalsveen and Bjørn Heine Strand

Objective: This study aimed to explore the magnitude and significance of associations among nutritional status, functional status, comorbidities, age, and gender in older adults receiving assistance from the in-home nursing care service.

Method: In this cross-sectional study, 210 home-dwelling persons 65 years or older who received in-home nursing care service were evaluated. Demographic variables, nutritional status, comorbidities, and the dependency levels of activities of daily living were analyzed. To assess the correlation among the factors that influence nutritional status, a theoretical model was developed and adjusted using the path analysis model.

Results: The primary finding is that functional status is directly associated with nutritional status (β = 0.32; p < 0.001) and severity of comorbidities is indirectly associated with nutritional status (β = −0.07; p < 0.017).
Conclusion: The elicited outcomes in this study reinforce the concept that nutritional status is linked with functional status in older adults receiving in-home care nursing service.

Luana Lemos Leão, Knut Engedal, Renato Sobral Monteiro-Junior, Gro Gujord Tangen and Maria Krogseth

Abstract

Tom Borza, Magnus Harneshaug, Lene Kirkhus, Jūratė Šaltytė Benth, Geir Selbæk, Sverre Bergh, Marit Slaaen

Abstract: Psychotic symptoms, defined as the occurrence of delusions or hallucinations, are frequent in Alzheimer disease (AD with psychosis, AD + P). AD + P affects ~50% of individuals with AD, identifies a subgroup with poor outcomes, and is associated with a greater degree of cognitive impairment and depressive symptoms, compared to subjects without psychosis (AD − P). Although the estimated heritability of AD + P is 61%, genetic sources of risk are unknown. We report a genome-wide meta-analysis of 12,317 AD subjects, 5445 AD + P. Results showed common genetic variation accounted for a significant portion of heritability. Two loci, one in ENPP6 (rs9994623, O.R. (95%CI) 1.16 (1.10, 1.22), p = 1.26 × 10−8) and one spanning the 3′-UTR of an alternatively spliced transcript of SUMF1 (rs201109606, O.R. 0.65 (0.56–0.76), p = 3.24 × 10−8), had genome-wide significant associations with AD + P. Gene-based analysis identified a significant association with APOE, due to the APOE risk haplotype ε4. AD + P demonstrated negative genetic correlations with cognitive and educational attainment and positive genetic correlation with depressive symptoms. We previously observed a negative genetic correlation with schizophrenia; instead, we now found a stronger negative correlation with the related phenotype of bipolar disorder. Analysis of polygenic risk scores supported this genetic correlation and documented a positive genetic correlation with risk variation for AD, beyond the effect of ε4. We also document a small set of SNPs likely to affect risk for AD + P and AD or schizophrenia. These findings provide the first unbiased identification of the association of psychosis in AD with common genetic variation and provide insights into its genetic architecture.

Mary Ann A. DeMichele-Sweet, Lambertus Klei, Byron Creese, Janet C. Harwood, Elise A. Weamer, Lora McClain, Rebecca Sims, Isabel Hernandez, Sonia Moreno-Grau, Lluís Tárraga, Mercè Boada, Emilio Alarcón-Martín, Sergi Valero, NIA-LOAD Family Based Study Consortium, Alzheimer’s Disease Genetics Consortium (ADGC), Yushi Liu, Basavaraj Hooli, Dag Aarsland, Geir Selbaek, Sverre Bergh, Arvid Rongve, Ingvild Saltvedt, Håvard K. Skjellegrind, Bo Engdahl, Eystein Stordal, Ole A. Andreassen, Srdjan Djurovic, Lavinia Athanasiu, Davide Seripa, Barbara Borroni, Diego Albani, Gianluigi Forloni, Patrizia Mecocci, Alessandro Serretti, Diana De Ronchi, Antonis Politis, Julie Williams, Richard Mayeux, Tatiana Foroud, Agustin Ruiz, Clive Ballard, Peter Holmans, Oscar L. Lopez, M. Ilyas Kamboh, Bernie Devlin & Robert A. Sweet

Abstract: Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.

Itziar de Rojas […] Geir Selbæk […] Agustín Ruiz

Background: Sarcopenia is an age-related muscle disease primarily characterized by reductions in muscle strength that increases the risk of falls, fractures, cognitive impairment, and mortality. Exercise is currently preferred in prevention and treatment, but it is unknown how different habitual physical activity and sedentary behaviour patterns associate with sarcopenia status. The purpose of the present study was to compare associations of these patterns with probable sarcopenia in older adults.

Methods: In 3653 community-dwelling participants (51% women) aged 60–84 years from the seventh survey of the Tromsø Study, we assessed objective physical activity and sedentary behaviour collected over 8 days (ActiGraph wGT3X-BT Accelerometer), grip strength (Jamar+ Digital Dynamometer), five-repetition chair stands, and self-reported disease. We combined tertiles of sedentary (SED) time and moderate-to-vigorous physical activity (MVPA) to create nine different activity profiles (SEDHIGH, SEDMOD, and SEDLOW combined with MVPAHIGH, MVPAMOD, or MVPALOW). Multiple logistic regression models were used to examine how these profiles associated with probable sarcopenia, defined by low handgrip strength and/or slow chair stands time according to the revised European Working Group on Sarcopenia in Older People criteria.

Results: Probable sarcopenia was present in 227 (6.2%) participants. Men with probable sarcopenia had on average 35.3 min more SED time and 20 min less MVPA compared with participants without sarcopenia (P < 0.01 for all), while women with probable sarcopenia only had 18 min less MVPA (P < 0.001). Compared with the SEDHIGH–MVPALOW reference activity profile (714.2 min SED/day and 10.4 min MVPA/day), the SEDHIGH–MVPAMOD profile (697.1 min SED/day and 31.5 min MVPA/day) had significantly lower odds ratio (OR) for probable sarcopenia (OR 0.17, 95% confidence interval [CI] 0.08–0.35), while the SEDLOW–MVPALOW profile (482.9 min SED/day and 11.0 min MVPA/day) did not (OR 0.72, 95% CI 0.47–1.11). These findings were not influenced by age, sex, smoking, or self-reported diseases, and higher levels of MVPA did not further decrease ORs for probable sarcopenia.

Conclusions: Older adults who achieve moderate amounts of MVPA have reduced odds for probable sarcopenia, even when they have high sedentary time. Those with low sedentary time did not have reduced odds for probable sarcopenia when they also had low amounts of MVPA. These findings need confirmation in longitudinal studies but suggest that interventions for preventing sarcopenia should prioritize increasing MVPA over reducing sedentary behaviour.

Jonas Johansson, Bente Morseth, David Scott, Bjørn Heine Strand, Laila A Hopstock, Sameline Grimsgaard

Introduction: The aims were to examine if the total and item scores on the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) and self-reported memory problems differed between older women and men, and if self-reported memory problems were associated with scores on the 2 tests. Methods: We included 309 home-dwelling people aged 70 years and older, 155 women, mean age 75.6 (SD 4.1) years, and 154 men, mean age 76.0 (SD 4.6) years. They were examined with MoCA and MMSE, and they answered 2 questions: “have you experienced any memory problems” and “have you experienced significant memory problems the last 5 years?” Results: The participants scored significantly higher on the MMSE (women 28.0 [1.8], men 28.4 [1.4]) than on MoCA (women 24.6 [3.3], men 24.3 [3.1]). Spearman’s rho was 0.36 between the tests. Women scored significantly higher than men on delayed recall of MoCA (3.0 [1.6] vs. 2.4 [1.6]), whereas men scored significantly higher on visuoconstruction (3.8 [1.2] vs. 3.5 [1.0]) and serial subtraction on MoCA (2.7 [0.6] vs. 2.5 [0.8]) and serial sevens on MMSE (4.5 [0.8] vs. 4.1 [1.1]). Multivariate linear regression analyses revealed that female sex, younger age, and higher education were associated with a higher score on MoCA, whereas age and education were associated with a higher score on MMSE. About half of the participants (no sex difference) had experienced significant memory problems the last 5 years, and they had significantly lower scores on both tests. Conclusions: The MoCA score was associated with sex, age, and education, whereas sex did not influence the MMSE score. The question “have you experienced significant memory problems the last 5 years?” may be useful to evaluate older people’s cognition.

Knut Engedal, Linda Gjøra, Thea Bredholt, Pernille Thingstad, Gro Gujord Tangen, Linda Ernstsen, Geir Selbæk

Background: As the population of older adults continues to grow, changes in alcohol consumption are important to monitor because an increase may have public health consequences. Rates of alcohol use vary with geographical location. The aim of this study was to examine trends in alcohol consumption among older adults in a geographically defined area in Norway, especially changing sex differences in drinking patterns over a 22-year period.
Methods: Repeated cross-sectional survey (in 1994-95, 2007-08, and 2015-16) of a general population of older adults. Eligible for this study were 20,939 participants (aged 60-99 years). The data were analysed using generalized estimating equations, stratified by age and sex. Alcohol consumption and drinking patterns were assessed, using an adaptation of the AUDIT-C.
Results: Between 1994 and 2016, there has been a significant increase in the proportion of current drinkers among older adults. Furthermore, the probability of frequent drinking (alcohol consumption at least twice weekly) increased significantly between 1994 and 2016, particularly among older women; OR 8.02 (CI 5.97-10.79) and OR 5.87 (CI 4.00-8.63) in the age groups 60-69 and 70+ respectively for women, and OR 4.13 (CI 3.42-4.99) and OR 3.10 (CI 2.41-3.99), in the age groups 60-69 and 70+ respectively for men. The majority of older adults drank small amounts of alcohol on typical drinking days, but there was an increasing probability of drinking three drinks or more on each occasion over the study period, except among women aged 70+ years.
Conclusions: Among older adults in Norway, alcohol consumption in terms of frequency and quantity on typical drinking days has increased considerably from 1996 to 2016. This change is in the opposite direction of what has been reported among younger adults. The gap between women and men in frequent drinking has been markedly narrowed, which indicate that women’s drinking patterns are approaching those of men. This may involve a need to change alcohol policy in Norway to more targeted interventions aimed at older people.

Line Tegner Stelander, Anne Høye, Jørgen G Bramness, Geir Selbæk, Linn-Heidi Lunde, Rolf Wynn, Ole Kristian Grønli

Abstract: Virtual reality-based exercise (exergames) improves cognition of the elderly but the neurophysiological effects are poorly understood. The hypothesis herein established is that an ultrafast neurophysiological adaptation occurs in prefrontal cortex of elderly after completion of a single exergames session. To reinforce the aforementioned hypothesis, individuals living in a Long-Term Care Home (LTCH) participated in the study and were randomly allocated into two groups (Virtual Reality Group, VRG, n=5; and Active Control Group, ACG n=5). VRG performed six exercises with exergames and ACG performed exercises with the same VRG movements but with no virtual reality. Assessment of frontal cortical activity at rest and during cognitive testing via electroencephalographic activity (EEG) was performed before and immediately after the intervention. Significant decrease in relative power of EEG (RPEEG) Beta brainwave (-29±18%) in the left prefrontal cortex of VRG compared to ACG (4±9%) (p=0.007). A slight improvement on semantic fluency in VRG (ES=0.21) was noted. An ultrafast prefrontal cortical adaptation may occur as an effect of a single exergames session, causing a small improvement on cognition of institutionalized elderly.

Mariana Rocha Alves, Knut Engedal, Jerson Laks, Vinícius Dias Rodrigues, Lara S.F. Carneiro, Ana Carolina de Mello Alves Rodrigues, Alfredo Maurício B. de Paula, Renato Sobral Monteiro-Juniora