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.

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.

Umbrella review and Delphi study on modifiable factors for dementia risk reduction.

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the "LIfestyle for BRAin health" (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta-analyses with a two-round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk scores need systematic updates based on emerging evidence. Future studies will validate the updated LIBRA score in different cohorts. HIGHLIGHTS: An umbrella review was combined with opinions of 18 dementia experts. Various candidate targets for dementia risk reduction were identified. Experts prioritized hearing impairment, social contact, and sleep. Re-assessment of dementia risk scores is encouraged. Future work should evaluate the predictive validity of updated risk scores.

Diagnostic accuracy of brain age prediction in a memory clinic population and comparison with clinically available volumetric measures.

The aim of this study was to assess the diagnostic validity of a deep learning-based method estimating brain age based on magnetic resonance imaging (MRI) and to compare it with volumetrics obtained using NeuroQuant (NQ) in a clinical cohort. Brain age prediction was performed on minimally processed MRI data using deep convolutional neural networks and an independent training set. The brain age gap (difference between chronological and biological age) was calculated, and volumetrics were performed in 110 patients with dementia (Alzheimer's disease, frontotemporal dementia (FTD), and dementia with Lewy bodies), and 122 with non-dementia (subjective and mild cognitive impairment). Area-under-the-curve (AUC) based on receiver operating characteristics and logistic regression analyses were performed. The mean age was 67.1 (9.5) years and 48.7% (113) were females. The dementia versus non-dementia sensitivity and specificity of the volumetric measures exceeded 80% and yielded higher AUCs compared to BAG. The explained variance of the prediction of diagnostic stage increased when BAG was added to the volumetrics. Further, BAG separated patients with FTD from other dementia etiologies with > 80% sensitivity and specificity. NQ volumetrics outperformed BAG in terms of diagnostic discriminatory power but the two methods provided complementary information, and BAG discriminated FTD from other dementia etiologies.

Dementia and mild cognitive impairment in older people in Trøndelag. / Demens og mild kognitiv svikt hos eldre personer i Trøndelag.

BACKGROUND: The number of people with dementia is expected to triple by 2050. We present figures showing the prevalence of dementia and mild cognitive impairment in Trondheim, and show how weighting for non-response and nursing home residency affects these figures when comparing Trondheim with Nord-Trøndelag. MATERIAL AND METHOD: In the fourth data collection in the Trøndelag Health Study (HUNT4) in the Norwegian county of Trøndelag, people aged 70 and over in Trondheim were invited to participate in HUNT4 Trondheim 70+. The participants were interviewed and underwent cognitive testing. A diagnostic team diagnosed dementia and mild cognitive impairment. Weights adjusting for non-response bias were used in the comparison of Trondheim and Nord-Trøndelag. RESULTS: The prevalence of dementia in Trondheim was estimated at 16.2 % for the age group 70 years and over, after weighting for non-response bias with regard to age, sex, education and proportion of nursing home residents. Unadjusted dementia prevalence was 21.0 % in Trondheim and 15.7 % in Nord-Trøndelag. After weighting, the prevalence was almost identical in the two samples. INTERPRETATION: Weighting for non-response is crucial for obtaining representative figures in prevalence studies of dementia.

Normative Scores on the Norwegian Version of the Mini-Mental State Examination.

BACKGROUND: The Mini-Mental State Examination (MMSE), a simple test for measuring global cognitive function, is frequently used to evaluate cognition in older adults. To decide whether a score on the test indicates a significant deviation from the mean score, normative scores should be defined. Moreover, because the test may vary depending on its translation and cultural differences, normative scores should be established for national versions of the MMSE. OBJECTIVE: We aimed to examine normative scores for the third Norwegian version of the MMSE. METHODS: We used data from two sources: the Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) and the Trøndelag Health Study (HUNT). After persons with dementia, mild cognitive impairment, and disorders that may cause cognitive impairment were excluded, the sample contained 1,050 cognitively healthy persons, 860 from NorCog, and 190 from HUNT, whose data we subjected to regression analyses. RESULTS: The normative MMSE score varied from 25 to 29, depending on years of education and age. More years of education and younger age were associated with higher MMSE scores, and years of education was the strongest predictor. CONCLUSION: Mean normative MMSE scores depend on test takers' years of education and age, with level of education being the strongest predictor.

Mobility and associations with levels of cerebrospinal fluid amyloid ß and tau in a memory clinic cohort.

Background: Mobility impairments, in terms of gait and balance, are common in persons with dementia. To explore this relationship further, we examined the associations between mobility and cerebrospinal fluid (CSF) core biomarkers for Alzheimer's disease (AD). Methods: In this cross-sectional study, we included 64 participants [two with subjective cognitive decline (SCD), 13 with mild cognitive impairment (MCI) and 49 with dementia] from a memory clinic. Mobility was examined using gait speed, Mini-Balance Evaluation Systems test (Mini-BESTest), Timed Up and Go (TUG), and TUG dual-task cost (TUG DTC). The CSF biomarkers included were amyloid-ß 42 (Aß42), total-tau (t-tau), and phospho tau (p-tau181). Associations between mobility and biomarkers were analyzed through correlations and multiple linear regression analyses adjusted for (1) age, sex, and comorbidity, and (2) SCD/MCI vs. dementia. Results: Aß42 was significantly correlated with each of the mobility outcomes. In the adjusted multiple regression analyses, Aß42 was significantly associated with Mini-BESTest and TUG in the fully adjusted model and with TUG DTC in step 1 of the adjusted model (adjusting for age, sex, and comorbidity). T-tau was only associated with TUG DTC in step 1 of the adjusted model. P-tau181 was not associated with any of the mobility outcomes in any of the analyses. Conclusion: Better performance on mobility outcomes were associated with higher levels of CSF Aß42. The association was strongest between Aß42 and Mini-BESTest, suggesting that dynamic balance might be closely related with AD-specific pathology.

The CERAD Word List Memory Test: Normative Data Based on a Norwegian Population-Based Sample of Healthy Older Adults 70 Years and Above. The HUNT Study.

BACKGROUND: The CERAD Word List Memory Test (WLMT) is widely used in the assessment of older adults with suspected dementia. Although normative data of the WLMT exist in many different regions of the world, normative data based on large population-based cohorts from the Scandinavian countries are lacking. OBJECTIVE: To develop normative data for the WLMT based on a large population-based Norwegian sample of healthy older adults aged 70 years and above, stratified by age, gender, and education. METHODS: A total of 6,356 older adults from two population-based studies in Norway, HUNT4 70 + and HUNT4 Trondheim 70+, were administered the WLMT. Only persons with normal cognitive function were included. We excluded persons with a diagnosis of mild cognitive impairment (MCI) and dementia, and persons with a history of stroke and/or depression. This resulted in 3,951 persons aged between 70 and 90 years, of whom 56.2% were females. Regression-based normative data were developed for this sample. RESULTS: Age, gender, and education were significant predictors of performance on the WLMT list-learning subtests and the delayed recall subtest, i.e., participants of younger age, female sex, and higher education level attained higher scores compared to participants of older age, male sex, and lower level of education. CONCLUSION: Regression-based normative data from the WMLT, stratified by age, gender, and education from a large population-based Norwegian sample of cognitively healthy older adults aged 70 to 90 years are presented. An online norm calculator is available to facilitate scoring of the subtests (in percentiles and z-scores).

The associations of psychological symptoms and cognitive patterns with pain and pain sensitization in people with hand osteoarthritis.

Objective: To examine whether psychological symptoms and cognitive patterns are associated with self-reported pain and pain sensitization in people with hand osteoarthritis (OA). Design: In the Nor-Hand study (n â€‹= â€‹300), people with hand OA self-reported psychological symptoms (Hospital Anxiety and Depression Scale), cognitive patterns (Pain catastrophizing Scale and Arthritis Self-Efficacy Scale) as well as their pain severity in hands, overall pain and multi-joint pain. Central pain sensitization was measured clinically by temporal summation and pressure pain threshold tests. We examined whether psychological symptoms and cognitive patterns were cross-sectionally associated with pain using linear regression. Beta coefficients (ß) per one standard deviation of the independent variable were presented. Stratified analyses were performed in cases of significant interactions (p â€‹< â€‹0.10). Results: Higher levels of anxiety, depressive symptoms and pain catastrophizing and low levels of self-efficacy were statistically significantly associated with higher levels of hand pain by Numeric Rating Scale (ߠ​= â€‹0.43, 0.48 and -0.57, respectively). Similar associations were found for overall pain, but not for measures of central pain sensitization. In stratified analyses, anxiety and depressive symptoms were more strongly related with pain in subgroups with younger age and higher comorbidity burden. Pain catastrophizing was more strongly related with pain in subgroups with younger age, overweight/obesity, higher comorbidity burden and poor sleep. Conclusion: Psychological symptoms and cognitive patterns were associated with self-reported OA pain, especially in people with younger age, overweight/obesity, higher comorbidity burden and poor sleep. No associations were found for psychological symptoms and cognitive patterns with pain sensitization.

Lifeworld perspectives of people with dementia: a meta-aggregation of qualitative studies.

OBJECTIVES: This meta-aggregation aims to interpret and synthesize present knowledge on the lifeworld perspectives of people with dementia and develop a model for guidance in clinical practice. METHOD: The data consist of four meta-syntheses describing different lifeworld perspectives in accordance with van Manen's existentials: lived relations, lived space, lived time and lived body. The meta-aggregation summarizes a range of views expressed by people with dementia in qualitative, interview-based studies, with the aim of generating a reliable model based on the studies' findings. RESULTS: In total, 88 studies among 1,191 persons with dementia were included. Sixteen areas of focus were found, representing four perspectives: (a) lived relations, consisting of connectedness, independence, equality and competence; (b) lived space, consisting of belonging, meaningfulness, safety and security, and autonomy; (c) lived time, consisting of being rooted in the past, being in the present, viewing the future and being in process; and (d) lived body, consisting of being functional, trustworthy, adaptable and presentable. A model shaped as a tree trunk captures the lifeworld perspectives of people with dementia. CONCLUSION: Sixteen areas were revealed from this meta-aggregation and form the basis of a model. This model may be used as a guide for health care personnel to ensure the overall lifeworld-perspectives of people with dementia in care for the target group and conduct lifeworld-preserving care with a person-centred approach.

Cohort profile: the Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) - a national research and quality registry with a biomaterial collection.

PURPOSE: The Norwegian Registry of Persons Assessed for Cognitive Symptoms (NorCog) was established to harmonise and improve the quality of diagnostic practice across clinics assessing persons with cognitive symptoms in Norwegian specialist healthcare units and to establish a large research cohort with extensive clinical data. PARTICIPANTS: The registry recruits patients who are referred for assessment of cognitive symptoms and suspected dementia at outpatient clinics in Norwegian specialist healthcare units. In total, 18 120 patients have been included in NorCog during the period of 2009-2021. The average age at inclusion was 73.7 years. About half of the patients (46%) were diagnosed with dementia at the baseline assessment, 35% with mild cognitive impairment and 13% with no or subjective cognitive impairment; 7% received other specified diagnoses such as mood disorders. FINDINGS TO DATE: All patients have a detailed baseline characterisation involving lifestyle and demographic variables; activities of daily living; caregiver situation; medical history; medication; psychiatric, physical and neurological examinations; neurocognitive testing; blood laboratory work-up; and structural or functional brain imaging. Diagnoses are set according to standardised diagnostic criteria. The research biobank stores DNA and blood samples from 4000 patients as well as cerebrospinal fluid from 800 patients. Data from NorCog have been used in a wide range of research projects evaluating and validating dementia-related assessment tools, and identifying patient characteristics, symptoms, functioning and needs, as well as caregiver burden and requirement of available resources. FUTURE PLANS: The finish date of NorCog was originally in 2029. In 2021, the registry's legal basis was reformalised and NorCog got approval to collect and keep data for as long as is necessary to achieve the purpose of the registry. In 2022, the registry underwent major changes. Paper-based data collection was replaced with digital registration, and the number of variables collected was reduced. Future plans involve expanding the registry to include patients from primary care centres.

Blood pressure trajectories over 35 years and dementia risk: A retrospective study: The HUNT study.

High blood pressure is a well-established risk factor of dementia. However, the timing of the risk remains controversial. The aim of the present study was to compare trajectories of systolic blood pressure (SBP) over a 35-year follow-up period in the Health Survey in Trøndelag (HUNT) from study wave 1 to 4 in people with and without a dementia diagnosis at wave 4 (HUNT4). This is a retrospective cohort study of participants aged ≥ 70 years in HUNT4, where 9,720 participants were assessed for dementia. In the HUNT study all residents aged ≥ 20 years have been invited to four surveys: HUNT1 1984-86, HUNT2 1995-97, HUNT3 2006-08 and HUNT4 2017-19. The study sample was aged 70-102 years (mean 77.6, SD 6.0) at HUNT4, 54% were women and 15.5% had dementia, 8.8% had Alzheimer's disease (AD), 1.6% had vascular dementia (VaD) and 5.1% had other types of dementia. Compared to those without dementia at HUNT4, those with dementia at HUNT4 had higher SBP at HUNT1 and HUNT2, but lower SBP at HUNT4. These differences at HUNT1 and 2 were especially pronounced among women. Results did not differ across birth cohorts. For dementia subtypes at HUNT4, the VaD group had a higher SBP than the AD group at HUNT2 and 3. Age trajectories in SBP showed that the dementia group experienced a steady increase in SBP until 65 years of age and a decrease from 70 to 90 years. SBP in the no- dementia group increased until 80 years before it leveled off from 80 to 90 years. The present study confirms findings of higher midlife SBP and lower late-life SBP in people with dementia. This pattern may have several explanations and it highlights the need for close monitoring of BP treatment in older adults, with frequent reappraisal of treatment needs.

Brain Morphometric Correlates of Depressive Symptoms among Patients with and without Dementia.

Introduction: Findings regarding brain morphometry among patients with dementia and concomitant depressive symptoms have been inconsistent. Thus, the aim of the present study was to test the hypothesis that dementia and concomitant depressive symptoms are associated with structural brain changes in the temporal lobe measured with structural magnetic resonance imaging (MRI). Methods: A sample of 492 patients from Norwegian memory clinics (n = 363) and Old Age Psychiatry services (n = 129) was studied. The assessment included the Cornell Scale for Depression in Dementia (CSDD), Instrumental Activities of Daily Living Scale, Mini Mental State Examination, and MRI of the brain, processed with FreeSurfer to derive ROI measures of cortical thickness, volume, and area using the Desikan-Killiany parcellation, as well as subcortical volumes. Dementia was diagnosed according to ICD-10 research criteria. Correlates of brain morphometry using multiple linear regression were examined. Results: Higher scores on the CSDD were associated with larger cortical volume (ß = 0.125; p value = 0.003) and area of the left isthmus of the cingulate gyrus (ß = 0.151; p value = <0.001) across all patients. Inclusion of an interaction term (dementia × CSDD) revealed a smaller area in the left temporal pole (ß = -0.345; p value = 0.001) and right-transverse temporal cortex (ß = -0.321; p value = 0.001) in patients with dementia and depressive symptoms. Discussion/Conclusion: We confirm the previous findings of structural brain changes in temporal regions among patients with dementia and concomitant depressive symptoms. This may contribute to a better understanding of the mechanisms underlying depression in dementia. To the best of our knowledge, this is the largest study conducted on this topic to date.

Family' members experiences of their older relative's alcohol and substance misuse.

BACKGROUND: Alcohol consumption in Norway and much of the western world has increased during the past decades, in particular among older adults (> 65 years). Although living with a family member's alcohol misuse has been shown to have a significant deleterious health impact, research on this topic is both lacking and urgently needed to develop targeted health services. AIM: To generate knowledge of how family members are affected by their older relatives' alcohol and other substance misuse problems. METHOD: In 2020, 17 individual interviews were carried out with the wives and adult children of older adults with alcohol and other substance misuse problems. Data were analysed using content analysis. FINDINGS: Analyses revealed two main themes; the impact of living with psychological stress over time, and the impact over time on family relationships and functioning. Both included four subthemes, representing different dimensions of participants' experiences of the impact of their older relative's alcohol and substance misuse. CONCLUSION: The challenges family members experienced through ongoing exposure to their relatives' alcohol and/or other substance misuse increased over time. These experiences had significant negative consequences for their health and life situation.

Hippocampal Atrophy Subtypes of Alzheimer's Disease Using Automatic MRI in a Memory Clinic Cohort: Clinical Implications.

INTRODUCTION: One pathological hallmark of Alzheimer's disease (AD) is atrophy of medial temporal brain regions that can be visualized on magnetic resonance imaging (MRI), but not all patients will have atrophy. The aim was to use MRI to categorize patients according to their hippocampal atrophy status and to present prevalence of the subtypes, difference in clinical symptomatology and progression, and factors associated with hippocampal subtypes. METHODS: We included 215 patients with AD who had been assessed with the clinically available MRI software NeuroQuant (NQ; CorTechs labs/University of California, San Diego, CA, USA). NQ measures the hippocampus volume and calculates a normative percentile. Atrophy was regarded to be present if the percentile was ≤5. Demographics, cognitive measurements, AD phenotypes, apolipoprotein E status, and results from cerebrospinal fluid and amyloid positron emission tomography analyses were included as explanatory variables of the hippocampal subtypes. RESULTS: Of all, 60% had no hippocampal atrophy. These patients were younger and less cognitively impaired concerning global measures, memory function, and abstraction but impaired concerning executive, visuospatial, and semantic fluency, and more of them had nonamnestic AD, compared to those with hippocampal atrophy. No difference in progression rate was observed between the two groups. In mild cognitive impairment patients, amyloid pathology was associated with the no hippocampal atrophy group. CONCLUSION: The results have clinical implications. Clinicians should be aware of the large proportion of AD patients presenting without atrophy of the hippocampus as measured with this clinical MRI method in the diagnostic set up and that nonamnestic phenotypes are more common in this group as compared to those with atrophy. Furthermore, the findings are relevant in clinical trials.

The Montreal Cognitive Assessment: Normative Data from a Large, Population-Based Sample of Cognitive Healthy Older Adults in Norway-The HUNT Study.

BACKGROUND: Several studies have found that normative scores on the Montreal Cognitive Assessment Scale (MoCA) vary depending on the person's education and age. The evidence for different normative scores between sexes is poor. OBJECTIVE: The main aim of the study was to determine normative scores on the MoCA for Norwegian older adults stratified by educational level, age, and sex. In addition, we aimed to explore sex differences in greater detail. METHODS: From two population-based studies in Norway, we included 4,780 people age 70 years and older. People with a diagnosis of dementia or mild cognitive impairment, a history of stroke, and depression were excluded. Trained health personnel tested the participants with the MoCA. RESULTS: The mean MoCA score varied between 22 and 27 and was highest among women 70-74 years with education >13 years and lowest among men age 85 and older with education ≤10 years. Education, age, and sex were significant predictors of MoCA scores. CONCLUSION: In the present study of cognitively healthy Norwegian adults 70 years and older, we found that the normative score on the MoCA varied between 22 and 27 depending on a person's education, age, and sex. We suggest that normative scores should be determined taking these three variables into consideration.

Associations between unmet needs for daytime activities and company and scores on the Neuropsychiatric Inventory-Questionnaire in people with dementia: a longitudinal study.

OBJECTIVES: To examine prospectively the association between unmet needs for daytime activities and company and behavioural and psychological symptoms of dementia. METHODS: We included 451 people with mild or moderate dementia, from eight European countries, who were assessed three times over 12 months. Unmet needs were measured with the Camberwell Assessment of Need for the Elderly. Three sub-syndromes of the Neuropsychiatric Inventory-Questionnaire were regressed, one-by-one, against unmet needs for daytime activities and company, adjusting for demographic and clinical-functional covariates. RESULTS: Unmet needs for daytime activities were associated with more affective symptoms at baseline, six and twelve months, mean 0.74 (p < 0.001), 0.76 (p < 0.001) and 0.78 (p = 0.001) points higher score respectively, and with more psychotic symptoms at baseline (mean 0.39 points, p = 0.007) and at six months follow-up (mean 0.31 points, p = 0.006). Unmet needs for company were associated with more affective symptoms at baseline, six and twelve months, mean 0.44 (p = 0.033), 0.67 (p < 0.001) and 0.91 (p < 0.001) points higher score respectively, and with more psychotic symptoms at baseline (mean 0.40 points, p = 0.005) and at six months (mean 0.35 points, p = 0.002) follow-up. CONCLUSION: Interventions to reduce unmet needs for daytime activities and company could reduce affective and psychotic symptoms in people with dementia.