Clinically feasible automated MRI volumetry of the brain as a prognostic marker in subjective and mild cognitive impairment.

Background/aims: The number of patients suffering from cognitive decline and dementia increases, and new possible treatments are being developed. Thus, the need for time efficient and cost-effective methods to facilitate an early diagnosis and prediction of future cognitive decline in patients with early cognitive symptoms is becoming increasingly important. The aim of this study was to evaluate whether an MRI based software, NeuroQuant® (NQ), producing volumetry of the hippocampus and whole brain volume (WBV) could predict: (1) conversion from subjective cognitive decline (SCD) at baseline to mild cognitive impairment (MCI) or dementia at follow-up, and from MCI at baseline to dementia at follow-up and (2) progression of cognitive and functional decline defined as an annual increase in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score. Methods: MRI was performed in 156 patients with SCD or MCI from the memory clinic at Oslo University Hospital (OUH) that had been assessed with NQ and had a clinical follow-up examination. Logistic and linear regression analyses were performed with hippocampus volume and WBV as independent variables, and conversion or progression as dependent variables, adjusting for demographic and other relevant covariates including Mini-Mental State Examination-Norwegian Revised Version score (MMSE-NR) and Apolipoprotein E ɛ4 (APOE ɛ4) carrier status. Results: Hippocampus volume, but not WBV, was associated with conversion to MCI or dementia, but neither were associated with conversion when adjusting for MMSE-NR. Both hippocampus volume and WBV were associated with progression as measured by the annual change in CDR-SB score in both unadjusted and adjusted analyses. Conclusion: The results indicate that automated regional MRI volumetry of the hippocampus and WBV can be useful in predicting further cognitive decline in patients with early cognitive symptoms.

Longitudinal Patterns of Systolic Blood Pressure, Diastolic Blood Pressure, Cardiorespiratory Fitness, and Their Association With Dementia Risk: The HUNT Study.

BACKGROUND: High blood pressure and poor cardiorespiratory fitness are independent risk factors for dementia. However, few studies have examined if combined longitudinal patterns of these modifiable risk factors are associated with dementia risk. METHODS: In this prospective cohort study, we used data from the population-based Trøndelag Health (HUNT) Study, Norway. We applied group-based multidimensional trajectory modeling to identify age-specific multidimensional trajectories of SBP, DBP, and estimated cardiorespiratory fitness across 3 surveys (HUNT1, 1984-1986 to HUNT3, 2006-2008). Dementia was diagnosed in the HUNT4 70+ substudy in 2017-2019. We used multivariate logistic regression to estimate odds ratios (ORs) and risk differences (RDs) of dementia. RESULTS: In total, 7 594 participants (54.9% women) were included, with a mean age of 44.7 (SD 6.3) years at HUNT1. Dementia was diagnosed in 1 062 (14.0%) participants. We identified 2 multidimensional trajectories throughout adulthood within 3 age groups: one with higher systolic blood pressure (SBP) and diastolic blood pressure (DBP), and lower estimated cardiorespiratory fitness (the poorer group), and one with lower SBP and DBP, and higher cardiorespiratory fitness (the better group). After adjustment for sex, apolipoprotein E ε4 status, education, marital status, and diabetes, the better group had consistently lower risk of dementia in all age groups with the lowest OR in the middle-aged group of 0.63 (95% confidence intervals [95% CI]: 0.51, 0.78) with corresponding RD of -0.07 (95% CI: -0.10, -0.04). CONCLUSIONS: Having a beneficial multidimensional trajectory of SBP, DBP, and cardiorespiratory fitness in adulthood was associated with reduced dementia risk. Aiming for optimal SBP, DBP, and estimated cardiorespiratory fitness throughout adulthood may reduce dementia risk.

Constructing personalized characterizations of structural brain aberrations in patients with dementia using explainable artificial intelligence.

Deep learning approaches for clinical predictions based on magnetic resonance imaging data have shown great promise as a translational technology for diagnosis and prognosis in neurological disorders, but its clinical impact has been limited. This is partially attributed to the opaqueness of deep learning models, causing insufficient understanding of what underlies their decisions. To overcome this, we trained convolutional neural networks on structural brain scans to differentiate dementia patients from healthy controls, and applied layerwise relevance propagation to procure individual-level explanations of the model predictions. Through extensive validations we demonstrate that deviations recognized by the model corroborate existing knowledge of structural brain aberrations in dementia. By employing the explainable dementia classifier in a longitudinal dataset of patients with mild cognitive impairment, we show that the spatially rich explanations complement the model prediction when forecasting transition to dementia and help characterize the biological manifestation of disease in the individual brain. Overall, our work exemplifies the clinical potential of explainable artificial intelligence in precision medicine.

Prevalence and Determinants of Diagnosed Dementia: A Registry Linkage Study Linking Diagnosis of Dementia in the Population-Based HUNT Study to Registry Diagnosis of Dementia in Primary Care and Hospitals in Norway.

Background: A timely diagnosis of dementia can be beneficial for providing good support, treatment, and care, but the diagnostic rate remains unknown and is probably low. Objective: To determine the dementia diagnostic rate and to describe factors associated with diagnosed dementia. Methods: This registry linkage study linked information on research-based study diagnoses of all-cause dementia and subtypes of dementias, Alzheimer's disease, and related dementias, in 1,525 participants from a cross-sectional population-based study (HUNT4 70+) to dementia registry diagnoses in both primary-care and hospital registries. Factors associated with dementia were analyzed with multiple logistic regression. Results: Among those with research-based dementia study diagnoses in HUNT4 70+, 35.6% had a dementia registry diagnosis in the health registries. The diagnostic rate in registry diagnoses was 19.8% among home-dwellers and 66.0% among nursing home residents. Of those with a study diagnosis of Alzheimer's disease, 35.8% (95% confidence interval (CI) 32.6-39.0) had a registry diagnosis; for those with a study diagnosis of vascular dementia, the rate was 25.8% (95% CI 19.2-33.3) and for Lewy body dementias and frontotemporal dementia, the diagnosis rate was 63.0% (95% CI 48.7-75.7) and 60.0% (95% CI 43.3-75.1), respectively. Factors associated with having a registry diagnosis included dementia in the family, not being in the youngest or oldest age group, higher education, more severe cognitive decline, and greater need for help with activities of daily living. Conclusions: Undiagnosed dementia is common, as only one-third of those with dementia are diagnosed. Diagnoses appear to be made at a late stage of dementia.

Prevalence and change in alcohol consumption in older adults over time, assessed with self-report and Phosphatidylethanol 16:0/18:1 -The HUNT Study.

BACKGROUND: Changes in alcohol consumption may affect older adults' health. We examined prevalence and changes in the alcohol consumption of older women and men (≥65 years) in Norway over a 24-year period. METHODS: Data from three population-based health surveys (The Trøndelag Health Study-HUNT2 1995-97, HUNT3 2006-08, HUNT4 2017-19) were used. Alcohol consumption was measured using self-reported measures and an objective measure of alcohol consumption (Phosphatidylethanol 16:0/18:1, PEth). Self-reported lifetime abstinence, former drinking, current drinking, frequent drinking (≥4 times/week), and risk drinking (≥8 units/week) were measured. The PEth concentrations were stratified: <0.03 µmol/l (abstinence/very low level of alcohol consumption); >0.06 µmol/l (indicating >1 unit/day); >0.10 µmol/l (indicating >3 units/day), and >0.30 µmol/l (heavy alcohol consumption). RESULTS: In HUNT4, the prevalence of self-reported lifetime abstinence, frequent drinking, and risk drinking was 5.2%, 4.4%, and 5.6%, respectively, while prevalence of PEth <0.03 µmol/l was 68.1% and PEth >0.06 µmol/l was 21.2%. Over the course of the three surveys, the prevalence of self-reported lifetime abstinence decreased, while the prevalence of frequent drinking and risk drinking increased. Men were less often abstainers and more often frequent and risky drinkers than women in all three surveys. Gender differences for abstinence and current drinking reduced with time. From HUNT3 to HUNT4, the prevalence of PEth <0.03 µmol/l decreased, while the prevalence of PEth >0.06 µmol/l increased. Men compared to women, had less often PEth <0.03 µmol/l and more often PEth >0.06 and >0.10 µmol/l in HUNT3 and HUNT4. Women and men ≥75 years were just as likely to have PEth >0.30 µmol/l in HUNT4. The gender differences in PEth concentrations were reduced in HUNT4 among those aged 70-74 years or ≥75 years. CONCLUSION: Alcohol consumption has increased among Norwegian older adults over a 24-year period, but at a slower pace during the last decade.

Genetic associations with psychosis and affective disturbance in Alzheimer's disease.

INTRODUCTION: Individuals with Alzheimer's disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study's goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes. METHODS: Genome-wide association meta-analysis of 9988 AD participants from six source studies with participants characterized for AD+P AD+A, and a joint phenotype (AD+A+P). RESULTS: AD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms. AD+A was positively correlated with anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereas AD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations. DISCUSSION: AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development. Highlights: It has long been known that psychotic and affective symptoms are often comorbid in individuals diagnosed with Alzheimer's disease. Here we examined for the first time the genetic architecture underlying this clinical observation, determining that psychotic and affective phenotypes in Alzheimer's disease are genetically correlated.Nevertheless, psychotic and affective phenotypes in Alzheimer's disease diverged in their genetic correlations with psychiatric phenotypes assessed in individuals without Alzheimer's disease. Psychosis in Alzheimer's disease was negatively genetically correlated with bipolar disorder and positively with depressive symptoms, whereas the affective phenotypes in Alzheimer's disease were positively correlated with anxiety disorder and more strongly correlated than psychosis with depressive symptoms.Psychosis in Alzheimer's disease, and the joint psychotic and affective phenotype, had significant estimated heritability, whereas the affective in AD did not.Examination of the loci most strongly associated with the psychotic, affective, or joint phenotypes revealed overlapping and unique associations.

Regional MRI volumetry using NeuroQuant versus visual rating scales in patients with cognitive impairment and dementia.

BACKGROUND AND PURPOSE: The aims were to compare the novel regional brain volumetric measures derived by the automatic software NeuroQuant (NQ) with clinically used visual rating scales of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal (GCA-f), and posterior atrophy (PA) brain regions, assessing their diagnostic validity, and to explore if combining automatic and visual methods would increase diagnostic prediction accuracy. METHODS: Brain magnetic resonance imaging (MRI) examinations from 86 patients with subjective and mild cognitive impairment (i.e., non-dementia, n = 41) and dementia (n = 45) from the Memory Clinic at Oslo University Hospital were assessed using NQ volumetry and with visual rating scales. Correlations, receiver operating characteristic analyses calculating area under the curves (AUCs) for diagnostic accuracy, and logistic regression analyses were performed. RESULTS: The correlations between NQ volumetrics and visual ratings of corresponding regions were generally high between NQ hippocampi/temporal volumes and MTA (r = -0.72/-0.65) and between NQ frontal volume and GCA-f (r = -0.62) but lower between NQ parietal/occipital volumes and PA (r = -0.49/-0.37). AUCs of each region, separating non-dementia from dementia, were generally comparable between the two methods, except that NQ hippocampi volume did substantially better than visual MTA (AUC = 0.80 vs. 0.69). Combining both MRI methods increased only the explained variance of the diagnostic prediction substantially regarding the posterior brain region. CONCLUSIONS: The findings of this study encourage the use of regional automatic volumetry in locations lacking neuroradiologists with experience in the rating of atrophy typical of neurodegenerative diseases, and in primary care settings.

Trajectories of Occupational Cognitive Demands and Risk of Mild Cognitive Impairment and Dementia in Later Life: The HUNT4 70+ Study.

BACKGROUND AND OBJECTIVES: The cognitive reserve hypothesis posits that cognitively stimulating work delays the onset of mild cognitive impairment (MCI) and dementia. However, the effect of occupational cognitive demands across midlife on the risk of these conditions is unclear. METHODS: Using a cohort study design, we evaluated the association between registry-based trajectories of occupational cognitive demands from ages 30-65 years and clinically diagnosed MCI and dementia in participants in the HUNT4 70+ Study (2017-19). Group-based trajectory modeling identified trajectories of occupational cognitive demands, measured by the routine task intensity (RTI) index (lower RTI indicates more cognitively demanding occupation) from the Occupational Information Network. Multinomial regression was implemented to estimate the relative risk ratios (RRRs) of MCI and dementia, after adjusting for age, sex, education, income, baseline hypertension, obesity, diabetes, psychiatric impairment, hearing impairment, loneliness, smoking status, and physical inactivity assessed at HUNT1-2 in 1984-1986 and 1995-1997. To handle missing data, we used inverse probability weighting to account for nonparticipation in cognitive testing and multiple imputation. RESULTS: Based on longitudinal RTI scores for 305 unique occupations, 4 RTI trajectory groups were identified (n = 7,003, 49.8% women, age range 69-104 years): low RTI (n = 1,431, 20.4%), intermediate-low RTI (n = 1,578, 22.5%), intermediate-high RTI (n = 2,601, 37.1%), and high RTI (n = 1,393, 19.9%). Participants in the high RTI group had a higher risk of MCI (RRR 1.74, 95% CI 1.41-2.14) and dementia (RRR 1.37, 95% CI 1.01-1.86), after adjusting for age, sex, and education compared with participants in the low RTI group. In a sensitivity analysis, controlling for income and baseline health-related factors, the point estimates were not appreciably changed (RRR 1.66, 95% CI 1.35-2.06 for MCI, and RRR 1.31, 95% CI 0.96-1.78 for dementia). DISCUSSION: People with a history of cognitively stimulating occupations during their 30s, 40s, 50s, and 60s had a lower risk of MCI and dementia older than 70 years, highlighting the importance of occupational cognitive stimulation during midlife for maintaining cognitive function in old age. Further research is required to pinpoint the specific occupational cognitive demands that are most advantageous for maintaining later-life cognitive function.

A longitudinal cohort study on the use of health and care services by older adults living at home with/without dementia before and during the COVID-19 pandemic: the HUNT study.

BACKGROUND: Older adults and people with dementia were anticipated to be particularly unable to use health and care services during the lockdown period following the COVID-19 pandemic. To better prepare for future pandemics, we aimed to investigate whether the use of health and care services changed during the pandemic and whether those at older ages and/or dementia experienced a higher degree of change than that observed by their counterparts. METHODS: Data from the Norwegian Trøndelag Health Study (HUNT4 70 + , 2017-2019) were linked to two national health registries that have individual-level data on the use of primary and specialist health and care services. A multilevel mixed-effects linear regression model was used to calculate changes in the use of services from 18 months before the lockdown, (12 March 2020) to 18 months after the lockdown. RESULTS: The study sample included 10,607 participants, 54% were women and 11% had dementia. The mean age was 76 years (SD: 5.7, range: 68-102 years). A decrease in primary health and care service use, except for contact with general practitioners (GPs), was observed during the lockdown period for people with dementia (p < 0.001) and those aged ≥ 80 years without dementia (p = 0.006), compared to the 6-month period before the lockdown. The use of specialist health services decreased during the lockdown period for all groups (p ≤ 0.011), except for those aged < 80 years with dementia. Service use reached levels comparable to pre-pandemic data within one year after the lockdown. CONCLUSION: Older adults experienced an immediate reduction in the use of health and care services, other than GP contacts, during the first wave of the COVID-19 pandemic. Within primary care services, people with dementia demonstrated a more pronounced reduction than that observed in people without dementia; otherwise, the variations related to age and dementia status were small. Both groups returned to services levels similar to those during the pre-pandemic period within one year after the lockdown. The increase in GP contacts may indicate a need to reallocate resources to primary health services during future pandemics. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov, with the identification number NCT04792086.

Exploring the lived experience: impact of dementia diagnosis on individuals with cognitive impairment - a qualitative study.

OBJECTIVE: Although knowledge about the experience of being diagnosed with dementia is limited, with the expected rise in dementia's prevalence in the coming decades, such knowledge is pivotal for the people diagnosed, their families, and healthcare planners. Thus, the aim of our study was to explore the experience of living with cognitive impairment and dementia and the impact of being diagnosed with dementia. METHOD: A qualitative design was applied. Participants were recruited based on age-adjusted values below ​​threshold values on the Montreal Cognitive Assessment Scale (i.e. 70-79 years, < 22; 80-89 years, < 21; 90 + years, < 20), and the sample ultimately included 15 participants: six with and nine without a documented dementia diagnosis. Qualitative content analysis was performed on the transcribed interviews in four steps to identify codes, categories, and the overall theme. RESULTS: Three major categories emerged from the interviews: (1) experiences with changes, (2) experiences with being diagnosed with dementia, and (3) existential experience. All participants with and most participants without a dementia diagnosis experienced changes in cognition. CONCLUSION: Our findings imply that being diagnosed with dementia is a relief because it explains observed cognitive and functional decreases and reduces confusion, shame and stigma. However, it also raises concerns about an unknown future. Most participants not diagnosed with dementia reported having little or no difficulty with everyday living and leading a fulfilling life. Those findings emphasise the significance of timely versus early diagnosis.

Meeting Summary of The NYO3 5th NO-Age/AD Meeting and the 1st Norway-UK Joint Meeting on Aging and Dementia: Recent Progress on the Mechanisms and Interventional Strategies.

Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a "Money Follows Cooperation agreement" between the 2 nations. The inaugural Norway-UK joint meeting on aging and dementia gathered leading experts on aging and dementia from the 2 nations to share their latest discoveries in related fields. Since aging is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular aging mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (eg, using NAD+ precursors). The meeting facilitated dialogue among policymakers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy aging.

The effect of a music-based caregiving intervention on pain intensity in nursing home patients with dementia: a cluster-randomized controlled study.

ABSTRACT: Treatment of chronic pain in patients with dementia is challenging because they have reduced ability to report pain and are particularly vulnerable to side effects of analgesics. Different types of music-based therapy have been recommended and are used as an alternative to analgesics, but the evidence is lacking. Therefore, we performed a cluster-randomized controlled study (RCT) to reduce pain intensity using music-based caregiving (MBC) over 8 weeks in nursing home patients with dementia and chronic pain. We also investigated if the amount of MBC and different chronic pain syndromes would impact on the effect. Of the 645 patients, 498 patients from 36 wards in 12 nursing homes were screened for dementia and pain. Using the Clinical Dementia Rating Scale and the Mobilization-Observation-Behavior-Intensity-Dementia Pain Scale (range 0-10), 279 (71% females, 42% severe dementia) nursing home patients were randomized to intervention group (n = 134, 18 wards) or control group (n = 145, 18 wards). The main outcome was change in pain intensity before and after the intervention. The study did not reveal any effect of MBC on pain intensity when compared with the control group (B = -0.15, 95% CI [-0.72 to 0.43]). No significant difference was found within the intervention group analyzing the impact of intervention time (B = 0.73, 95% CI [-0.55 to 2.02]) or chronic primary vs secondary pain syndromes (B = 0.45, 95% CI [-0.05 to 0.96]). Our data from this first RCT on music and pain intensity in patients with dementia and chronic pain did not find an effect of MBC on pain.

Oral symptoms in dying nursing home patients. Results from the prospective REDIC study.

BACKGROUND: The mouth is a central organ for communication and fluid intake, also for dying nursing home patients. This study describes the prevalence and severity of oral symptoms from nursing home admission until the day of perceived dying and the day of death. METHODS: A prospective, longitudinal cohort study including 696 patients who were admitted to 47 Norwegian nursing homes in 35 municipalities. During the first year of their stay, 189 died (27%), of whom 82 participants were assessed on the day they were perceived as dying and 134 on the day of death. Mouth care, nutrition, and bedsores were assessed with the Residents' Assessment Instrument for nursing homes (RAI-NH) and palliative care (RAI-PC). Pain intensity was assessed with the Mobilization-Observation-Behaviour-Intensity-Dementia-2 Pain Scale (MOBID-2). RESULTS: The proportion of patients with ≥ 6 oral symptoms increased from 16% when perceived as dying to 20% on the day of death (P = 0.001). On the day of death, xerostomia (66%), dysphagia (59%), and mastication problems (50%) were the most frequently observed oral symptoms. Only 16% received mouth care every hour and 12% were in pain during this procedure. Compared to people without dementia, those with a diagnosis of dementia at admission (N = 112, 86%) had xerostomia and mastication problems more frequently (50% vs. 73%; 32% vs. 56% (P = 0.038), respectively) on the day of death. CONCLUSIONS: The high extent of oral symptoms such as xerostomia, dysphagia, and mastication problems underline the need for systematic assessment and improved oral palliative care for dying nursing home patients with dementia. TRIAL REGISTRATION: Clinicaltrials.gov NCT01920100 08/08/2013. First submission to BMC oral 15/03/2023.

Trajectories of occupational physical activity and risk of later-life mild cognitive impairment and dementia: the HUNT4 70+ study.

Background: High levels of occupational physical activity (PA) have been linked to an increased risk of dementia. We assessed the association of trajectories of occupational PA at ages 33-65 with risk of dementia and mild cognitive impairment (MCI) at ages 70+. Methods: We included 7005 participants (49.8% were women, 3488/7005) from the HUNT4 70+ Study. Group-based trajectory modelling was used to identify four trajectories of occupational PA based on national registry data from 1960 to 2014: stable low (30.9%, 2162/7005), increasing then decreasing (8.9%, 625/7005), stable intermediate (25.1%, 1755/7005), and stable high (35.2%, 2463/7005). Dementia and MCI were clinically assessed in 2017-2019. We performed adjusted multinomial regression to estimate relative risk ratios (RRR) with 95% confidence intervals (CI) for dementia and MCI. Findings: 902 participants were diagnosed with dementia and 2407 were diagnosed with MCI. Absolute unadjusted risks for dementia and MCI were 8.8% (95% CI: 7.6-10.0) and 27.4% (25.5-29.3), respectively, for those with a stable low PA trajectory, 8.2% (6.0-10.4) and 33.3% (29.6-37.0) for those with increasing, then decreasing PA; while they were 16.0% (14.3-17.7) and 35% (32.8-37.2) for those with stable intermediate, and 15.4% (14.0-16.8) and 40.2% (38.3-42.1) for those with stable high PA trajectories. In the adjusted model, participants with a stable high trajectory had a higher risk of dementia (RRR 1.34, 1.04-1.73) and MCI (1.80, 1.54-2.11), whereas participants with a stable intermediate trajectory had a higher risk of MCI (1.36, 1.15-1.61) compared to the stable low trajectory. While not statistically significant, participants with increasing then decreasing occupational PA had a 24% lower risk of dementia and 18% higher risk of MCI than the stable low PA group. Interpretation: Consistently working in an occupation with intermediate or high occupational PA was linked to an increased risk of cognitive impairment, indicating the importance of developing strategies for individuals in physically demanding occupations to prevent cognitive impairment. Funding: This work was supported by the National Institutes of Health (R01AG069109-01) and the Research Council of Norway (296297, 262700, 288083).