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.

The impact of medication reviews by general practitioners on psychotropic drug use and behavioral and psychological symptoms in home-dwelling people with dementia: results from the multicomponent cluster randomized controlled LIVE@Home.Path trial.

BACKGROUND: There is limited knowledge regarding the process of deprescribing psychotropic drugs to people with dementia (PwD) conducted by general practitioners (GP). We investigated the impact of a multicomponent intervention, emphasizing medication reviews, on psychotropic drugs and behavioral and psychological symptoms (BPSD) in home-dwelling PwD and quantified change in patient-GP communication evaluated by their informal caregivers. METHODS: LIVE@Home.Path is a stepped-wedge closed-cohort cluster randomized controlled trial for people with mild to moderate dementia aged ≥65 and their informal caregivers (dyads) in Norway. Complementary to health care as usual (control condition), municipal coordinators implemented the multicomponent LIVE intervention: Learning, Innovation, Volunteer support, and Empowerment (including medication review by the PwD's regular GPs). Block-randomization was used to allocate dyads in three groups receiving the intervention sequentially in periods of 6 months duration. Prepandemic data from the first period is reported, resulting in a 1:2 intervention-to-control ratio. Primary outcome was change in psychotropic drug use. Secondary outcomes were changes in BPSD by Neuropsychiatric Inventory and Cornell Scale of Depression in Dementia and patient-GP communication by an adaption of the Clinical Global Impression of Change. RESULTS: Four hundred thirty-eight dyads were screened, 280 included, and 237 participated at 6 months (intervention group n=67; control condition n=170). At baseline, 63% used psychotropic medication regularly: antidementia drugs (47%), antidepressants (13%), hypnotics/sedatives (13%), antipsychotics (5%), and anxiolytics (2%). At 6 months, medication reviews were more frequently conducted in the intervention group compared to control (66% vs 42%, P=0.001). We found no differences regarding a change in drug use and BPSD. Patient-GP communication enhanced in the intervention group (mean score 0.95 [standard deviation 1.68] vs 0.41 [1.34], P=0.022). In the intervention group, control group, and overall sample, the informal caregivers of those who had their medications reviewed reported improved patient-GP communication compared to those who did not. CONCLUSIONS: Change in psychotropic drug use and BPSD did not differ, even though patient-GP communication improved with medication reviews. Restricted psychotropic drug use among PwD likely reflects more judicious prescribing practices in recent years. Nevertheless, medication reviews could be cultivated to optimize pharmacologic treatment for this complex population. TRIAL REGISTRATION: ClinicalTrials.gov : NCT04043364 ; registered 15/03/2019.

Impact of COVID-19 restrictions on behavioural and psychological symptoms in home-dwelling people with dementia: a prospective cohort study (PAN.DEM).

OBJECTIVES: To investigate the impact of the COVID-19 restrictions on behavioural and psychological symptoms of dementia (BPSD). DESIGN: Prospective cohort study (PAN.DEM) nested within the halted parent trial (LIVE@Home.Path). SETTING: Households in Norway immediate before and 6-9 weeks into the COVID-19 restrictions. PARTICIPANTS: 104 dyads (persons with mild to moderate dementia aged ≥65 and their informal carers) completed both prepandemic and pandemic assessments, among 237 in the parent trial. Mini-Mental Status Examination score 15-26 or Functional Assessment Staging score 3-7 covered dementia severity. MAIN OUTCOME MEASURES: Neuropsychiatric Inventory (NPI-12) total (range 0-144), psychosis (range 0-24), hyperactive behaviour (range 0-60) and mood subsyndrome (range 0-48) scores; Cornell Scale for Depression in Dementia (CSDD) total score (range 0-38). RESULTS: We found an overall increase in BPSD by NPI-12 total score comparing prepandemic to pandemic levels (median 16 IQR (4.5-29) to 20 (7-32.5), p=0.03) over a mean of 86 days (SD 19). NPI-12 total score worsened in 57 (55%) of people with dementia and was associated with postponed or averted contacts with healthcare professionals (logistic regression, OR 3.96, 95% CI 1.05 to 14.95). Psychosis subsyndrome levels increased (0 (0-3) to 0.5 (0-6), p=0.01) in 37 (36%) persons; this worsening was associated with partial insight (9.57, 1.14 to 80.71) and reduced informal carer contact (4.45, 1.01 to 19.71). Moreover, depressive symptoms increased as assessed by CSDD total score (5 (3-9) to 7 (4-12), p=0.01) and worsened for 56 (54%), which was inversely associated with psychotropic drugs on-demand (0.16, 0.03 to 0.75). CONCLUSIONS: BPSD worsened during the first months of the COVID-19 restrictions, most pronounced for psychosis and depression. These BPSD exacerbations have implications for pandemic policies, emphasising that restrictions must balance COVID-19 morbidity and mortality against dementia deterioration. TRIAL REGISTRATION NUMBER: NCT04043364; Results.

Diffusion tension imaging is a good tool for assessing patients with dementia and behavioral problems and discriminating them from other dementia patients.

BACKGROUND: Dementia is one of the leading public health concerns as the world's population ages. Although Alzheimer's disease (AD) is the most common dementia diagnosis among older patients, some patients have additional behavioral symptoms. It is therefore important to provide an exact diagnosis, both to provide the best possible treatment for patients and to facilitate better understanding. PURPOSE: To investigate whether magnetic resonance imaging (MRI) with fractional anisotropy (FA) can accurately find patients with behavioral symptoms within a group of AD patients. MATERIAL AND METHODS: Forty-five patients from the geriatric outpatient clinic were recruited consecutively to form a group of patients with AD and behavioral symptoms (AD + BS) and a control group of 50 patients with established AD. All patients had a full assessment for dementia to establish the diagnosis according to ICD-10. MRI included 3D anatomical recordings for morphometric measurements, DTI for fiber tracking, and quantitative assessment of regional white matter integrity. The DTI analyses included computing of the diffusion tensor and its derived FA index. RESULTS: We found a significant difference in FA values between the patient groups' frontal lobes. The FA was greater in the study group in both left (0.39 vs 0.09, p < 0.05) and right (0.40 vs 0.16, p < 0.05) frontal lobes. CONCLUSION: MRI with FA will find damage in frontal tracts and may be used as a diagnostic tool and be considered a robust tool for the recognizing different types of dementia in the future.

Neopterin and kynurenic acid as predictors of stroke recurrence and mortality: a multicentre prospective cohort study on biomarkers of inflammation measured three months after ischemic stroke.

BACKGROUND: Chronic low-grade inflammation is associated with both ischemic stroke and sedentary behaviour. The aim of this study was to investigate the predictive abilities of biomarkers of inflammation and immune modulation associated with sedentary behaviour for ischemic stroke recurrence and mortality in a stroke population. METHODS: Patients admitted to hospital for acute stroke were recruited to the prospective multicentre cohort study, the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study, from May 2015 until March 2017. Patients with ischemic stroke, blood samples available from the three-month follow-up, and no stroke recurrence before the three-month follow-up were included. Serum was analysed for C-reactive protein (CRP) with high-sensitive technique, and plasma for interleukin-6 (IL-6), neopterin, pyridoxic acid ratio index (PAr-index: 4-pyridoxic acid: [pyrioxal+pyridoxal-5'-phosphate]) and kynurenic acid (KA). Ischemic stroke recurrence and death were identified by the Norwegian Stroke Registry and the Cause of Death Registry until 31 December 2018. RESULTS: The study included 354 patients, 57% male, mean age 73 (SD 11) years, mean observation time 2.5 (SD 0.6) years, and median National Institute of Health Stroke Scale of 0 (IQR 1) at three months. CRP was associated with mortality (HR 1.40, CI 1.01, 1.96, p = 0.046), and neopterin was associated with the combined endpoint (recurrent ischemic stroke or death) (HR 1.52, CI 1.06, 2.20, p = 0.023), adjusted for age, sex, prior cerebrovascular disease, modified Rankin Scale, and creatinine. When adding neopterin and KA to the same model, KA was negatively associated (HR 0.57, CI 0.33, 0.97, p = 0.038), and neopterin was positively associated (HR 1.61, CI 1.02, 2.54, p = 0.040) with mortality. Patients with cardioembolic stroke at baseline had higher levels of inflammation at three months. CONCLUSION: Neopterin might be a valuable prognostic biomarker in stroke patients. The use of KA as a measure of anti-inflammatory capacity should be investigated further. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted on 08/01/2016.

Investigating novel biomarkers of immune activation and modulation in the context of sedentary behaviour: a multicentre prospective ischemic stroke cohort study.

BACKGROUND: Sedentary behaviour is associated with disease, but the molecular mechanisms are not understood. Valid biomarkers with predictive and explanatory properties are required. Therefore, we have investigated traditional and novel biomarkers of inflammation and immune modulation and their association to objectively measured sedentary behaviour in an ischemic stroke population. METHODS: Patients admitted to hospital with acute ischemic stroke were included in the multicentre Norwegian Cognitive Impairment After Stroke (Nor-COAST) study (n = 815). For this sub-study (n = 257), sedentary behaviour was registered 3 months after stroke using position transition data from the body-worn sensor, ActivPal®. Blood samples were analysed for high sensitive C-reactive protein (hsCRP), the cytokines interleukin-6 (IL-6) and 10 (IL-10), neopterin, tryptophan (Trp), kynurenine (kyn), kynurenic acid (KA), and three B6 vitamers, pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and pyridoxic acid (PA). The kynurenine/tryptophan ratio (KTR) and the pyridoxic acid ratio index (PAr = PA: PL + PLP) were calculated. RESULTS: Of the 815 patients included in the main study, 700 attended the three-month follow-up, and 257 fulfilled the inclusion criteria for this study. Sedentary time was significantly associated with levels of hsCRP, IL-6, neopterin, PAr-index, and KA adjusted for age, sex, waist circumference, and creatinine. In a fully adjusted model including all the significant biomarkers except hsCRP (because of missing values), sedentary time was independently positively associated with the PAr-index and negatively with KA. We did not find an association between sedentary behaviour, IL-10, and KTR. CONCLUSIONS: The PAr-index is known to capture several modes of inflammation and has previously shown predictive abilities for future stroke. This novel result indicates that the PAr-index could be a useful biomarker in future studies on sedentary behaviour and disease progression. KA is an important modulator of inflammation, and this finding opens new and exciting pathways to understand the hazards of sedentary behaviour. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted 08/01/2016.

Less Is More: The Impact of Deprescribing Psychotropic Drugs on Behavioral and Psychological Symptoms and Daily Functioning in Nursing Home Patients. Results From the Cluster-Randomized Controlled COSMOS Trial.

OBJECTIVE: To investigate the impact of medication reviews using collegial mentoring and systematic clinical evaluation on psychotropic prescriptions, behavioral and psychological symptoms of dementia (BPSD), and activities of daily living (ADL). DESIGN: Four-month multicenter, multicomponent, cluster-randomized, single-blinded controlled trial. SETTING: Thirty-three Norwegian nursing homes including 67 nursing home wards (clusters). PARTICIPANTS: A total of 723 enrolled patients, of which 428 participated in the study; 217 were randomized to the intervention and 211 to care as usual (control). INTERVENTION: The COSMOS intervention consisted of Communication, Systematic pain management, Medication reviews, Organization of activities, and Safety. During medication review, the nursing home physician evaluated treatment with colleagues systematically using the results from validated clinical assessments. MEASUREMENTS: Mean changes from baseline to month 4 in the number of prescribed psychotropic drugs (antipsychotics, anxiolytics, hypnotics or sedatives, antidepressants, and antidementia drugs); Neuropsychiatric Inventory Nursing Home Version (NPI-NH) and Cornell Scale of Depression in Dementia (CSDD); Lawton and Brody's Physical Self Maintenance Scale (PSMS). RESULTS: Compared to control, the mean change in prescribed psychotropic drugs was reduced both in total and regular number, while mean changes in NPI-NH and CSDD scores did not differ between the groups. Mean change in PSMS showed improvement in the intervention group, and deterioration in the control group. CONCLUSION: Medication reviews using collegial mentoring and systematic clinical evaluation led to safe deprescribing, as the reductions in psychotropic drug use did not negatively affect BPSD, while ADL improved.

Is long-bout sedentary behaviour associated with long-term glucose levels 3 months after acute ischaemic stroke? A prospective observational cohort study.

BACKGROUND AND PURPOSE: Sedentary behaviour is a risk factor for vascular disease and stroke patients are more sedentary than their age-matched peers. The association with glucose levels, as a potential mediator, is unclear, and we have investigated the association between long-bout sedentary behaviour and long-term glucose levels in stroke survivors. METHODS: This study uses data from the Norwegian Cognitive Impairment After Stroke study, a multicentre cohort study. The patients were recruited at hospital admission for acute stroke, and the follow-up was done at the outpatient clinic. Sedentary behaviour-being in a sitting or reclining position-was registered 3 months after stroke using position transition data from the body-worn sensor activPAL attached to the unaffected thigh. A MATLAB script was developed to extract activity data from 08:00 to 10:00 for 4 days and to categorise the data into four bout-length categories. The primary outcome was glycated haemoglobin (HbA1c), analysed at 3 months. Regression models were used to analyse the association between HbA1c and sedentary behaviour in the whole population and stratified based on a diagnosis of diabetes mellitus (DM). Age, body mass index and the use of antidiabetic drugs were added as covariates into the models. RESULTS: From a total of 815 included patients, 379 patients fulfilled the inclusion criteria for this study. We found no association between time in sedentary behaviour and HbA1c in the whole stroke population. We found time in sedentary behaviour in bouts of ≥90 min to be associated with a higher HbA1c in patients with DM. CONCLUSION: Long-bout sedentary time is associated with a higher HbA1c in patients with DM 3 months after ischaemic stroke. Future research should investigate the benefit of breaking up sedentary time as a secondary preventive measure. TRIAL REGISTRATION NUMBER: NCT02650531, https://clinicaltrials.gov/ct2/show/NCT02650531.

The Power of EEG to Predict Conversion from Mild Cognitive Impairment and Subjective Cognitive Decline to Dementia.

INTRODUCTION: The aim of this study was to examine if quantitative electroencephalography (qEEG) using the statistical pattern recognition (SPR) method could predict conversion to dementia in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHODS: From 5 Nordic memory clinics, we included 47 SCD patients, 99 MCI patients, and 67 healthy controls. EEGs analyzed with the SPR method together with clinical data recorded at baseline were evaluated. The patients were followed up for a mean of 62.5 (SD 17.6) months and reexamined. RESULTS: Of 200 participants with valid clinical information, 70 had converted to dementia, and 52 had developed Alzheimer's disease. Receiver-operating characteristic analysis of the EEG results as defined by a dementia index (DI) ranging from 0 to 100 revealed that the area under the curve was 0.78 (95% CI 0.70-0.85), corresponding to a sensitivity of 71%, specificity of 69%, and accuracy of 69%. A logistic regression analysis showed that by adding results of a cognitive test at baseline to the EEG DI, accuracy could improve. CONCLUSION: We conclude that applying qEEG using the automated SPR method can be helpful in identifying patients with SCD and MCI that have a high risk of converting to dementia over a 5-year period. As the discriminant power of the method is of moderate degree, it should be used in addition to routine diagnostic methods.

LIVE@Home.Path-innovating the clinical pathway for home-dwelling people with dementia and their caregivers: study protocol for a mixed-method, stepped-wedge, randomized controlled trial.

BACKGROUND: The global health challenge of dementia is exceptional in size, cost and impact. It is the only top ten cause of death that cannot be prevented, cured or substantially slowed, leaving disease management, caregiver support and service innovation as the main targets for reduction of disease burden. Institutionalization of persons with dementia is common in western countries, despite patients preferring to live longer at home, supported by caregivers. Such complex health challenges warrant multicomponent interventions thoroughly implemented in daily clinical practice. This article describes the rationale, development, feasibility testing and implementation process of the LIVE@Home.Path trial. METHODS: The LIVE@Home.Path trial is a 2-year, multicenter, mixed-method, stepped-wedge randomized controlled trial, aiming to include 315 dyads of home-dwelling people with dementia and their caregivers, recruited from 3 municipalities in Norway. The stepped-wedge randomization implies that all dyads receive the intervention, but the timing is determined by randomization. The control group constitutes the dyads waiting for the intervention. The multicomponent intervention was developed in collaboration with user-representatives, researchers and stakeholders to meet the requirements from the national Dementia Plan 2020. During the 6-month intervention period, the participants will be allocated to a municipal coordinator, the core feature of the intervention, responsible for regular contact with the dyads to facilitate L: Learning, I: Innovation, V: Volunteering and E: Empowerment (LIVE). The primary outcome is resource utilization. This is measured by the Resource Utilization in Dementia (RUD) instrument and the Relative Stress Scale (RSS), reflecting that resource utilization is more than the actual time required for caring but also how burdensome the task is experienced by the caregiver. DISCUSSION: We expect the implementation of LIVE to lead to a pathway for dementia treatment and care which is cost-effective, compared to treatment as usual, and will support high-quality independent living, at home. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04043364. Registered on 15 March 2019.

Cholinergic dysfunction, neurodegeneration, and amyloid-beta pathology in neurodegenerative diseases.

Cholinergic dysfunction is central in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). The electroencephalography-based acetylcholine index (EEG-Ach index) has been proposed as a biomarker of cholinergic dysfunction. However, it is unclear how the EEG-Ach index relates to amyloid-beta pathology and neurodegeneration. We investigated the association between the EEG-Ach index and cerebrospinal fluid (CSF) amyloid-beta, CSF total tau, cortical thickness, and hippocampal volume from magnetic resonance imaging (MRI), and cognition. A total of 127 patients with different neurodegenerative diseases were studied. The EEG-Ach index was calculated from quantitative EEG using statistical pattern recognition. The EEG-Ach index was associated with hippocampal volume and cortical thickness in frontal, temporal, and occipital cortices. Cross-sectional sub-analyses based on a small sample suggests that the EEG-Ach index increases the closest to AD dementia, downstream to amyloid-beta pathology, CSF total tau, and hippocampal volume. We conclude that cholinergic dysfunction correlates with atrophy in brain areas important for AD pathogenesis, and this association is more prominent in the dementia stage. These results together with previous studies from this project suggest that the EEG-Ach index may be a useful biomarker for cholinergic dysfunction, with value for differential diagnosis of dementia and monitoring patients at the dementia stage.

Changes in the left temporal microstate are a sign of cognitive decline in patients with Alzheimer's disease.

INTRODUCTION: Large-scale brain networks are disrupted in the early stages of Alzheimer's disease (AD). Electroencephalography microstate analysis, a promising method for studying brain networks, parses EEG signals into topographies representing discrete, sequential network activations. Prior studies indicate that patients with AD show a pattern of global microstate disorganization. We investigated whether any specific microstate changes could be found in patients with AD and mild cognitive impairment (MCI) compared to healthy controls (HC). MATERIALS AND METHODS: Standard EEGs were obtained from 135 HC, 117 patients with MCI, and 117 patients with AD from six Nordic memory clinics. We parsed the data into four archetypal microstates. RESULTS: There was significantly increased duration, occurrence, and coverage of microstate A in patients with AD and MCI compared to HC. When looking at microstates in specific frequency bands, we found that microstate A was affected in delta (1-4 Hz), theta (4-8 Hz), and beta (13-30 Hz), while microstate D was affected only in the delta and theta bands. Microstate features were able to separate HC from AD with an accuracy of 69.8% and HC from MCI with an accuracy of 58.7%. CONCLUSIONS: Further studies are needed to evaluate whether microstates represent a valuable disease classifier. Overall, patients with AD and MCI, as compared to HC, show specific microstate alterations, which are limited to specific frequency bands. These alterations suggest disruption of large-scale cortical networks in AD and MCI, which may be limited to specific frequency bands.

Oscillatory connectivity as a diagnostic marker of dementia due to Alzheimer's disease.

OBJECTIVE: Quantitative EEG power has not been as effective in discriminating between healthy aging and Alzheimer's disease as conventional biomarkers. But EEG coherence has shown promising results in small samples. The overall aim was to evaluate if EEG connectivity markers can discriminate between Alzheimer's disease, mild cognitive impairment, and healthy aging and to explore the early underlying changes in coherence. METHODS: EEGs were included in the analysis from 135 healthy controls, 117 patients with mild cognitive impairment, and 117 patients with Alzheimer's disease from six Nordic memory clinics. Principal component analysis was performed before multinomial regression. RESULTS: We found classification accuracies of above 95% based on coherence, imaginary part of coherence, and the weighted phase-lag index. The most prominent changes in coherence were decreased alpha coherence in Alzheimer's disease, which was correlated to the scores of the 10-word test in the Consortium to Establish a Registry for Alzheimer's Disease battery. CONCLUSIONS: The diagnostic accuracies for EEG connectivity measures are higher than findings from studies investigating EEG power and conventional Alzheimer's disease biomarkers. Furthermore, decreased alpha coherence is one of the earliest changes in Alzheimer's disease and associated with memory function. SIGNIFICANCE: EEG connectivity measures may be useful supplementary diagnostic classifiers.

EEG Theta Power Is an Early Marker of Cognitive Decline in Dementia due to Alzheimer's Disease.

BACKGROUND: Quantitative EEG (qEEG) power could potentially be used as a diagnostic tool for Alzheimer's disease (AD) and may further our understanding of the pathophysiology. However, the early qEEG power changes of AD are not well understood. OBJECTIVE: To investigate the early changes in qEEG power and the possible correlation with memory function and cerebrospinal fluid biomarkers. In addition, whether qEEG power could discriminate between AD, mild cognitive impairment (MCI), and older healthy controls (HC) at the individual level. METHODS: Standard EEGs from 138 HC, 117 MCI, and 117 AD patients were included from six Nordic memory clinics. All EEGs were recorded consecutively before the diagnosis and were not used for the consensus diagnosis. Absolute and relative power was calculated for both eyes closed and open condition. RESULTS: At group level using relative power, we found significant increases globally in the theta band and decreases in high frequency power in the temporal regions for eyes closed for AD and, to a lesser extent, for MCI compared to HC. Relative theta power was significantly correlated with multiple neuropsychological measures and had the largest correlation coefficient with total tau. At the individual level, the classification rate for AD and HC was 72.9% for relative power with eyes closed. CONCLUSION: Our findings suggest that the increase in relative theta power may be the first change in patients with dementia due to AD. At the individual level, we found a moderate classification rate for AD and HC when using EEGs alone.

Quantitative Electroencephalography Analyzed by Statistical Pattern Recognition as a Diagnostic and Prognostic Tool in Mild Cognitive Impairment: Results from a Nordic Multicenter Cohort Study.

AIM: To examine diagnostic and prognostic potential of quantitative electroencephalography (qEEG) analyzed by the statistical pattern recognition (SPR) method in patients with cognitive impairment. We compared the differential diagnostic ability of SPR to visual EEG analysis. Correlation between SPR findings and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers were evaluated. METHODS: It is a multicenter cohort study involving 129 patients, (mild cognitive impairment [MCI], AD, and healthy controls). Standardized EEG was performed at baseline. Patients were continuously clinically evaluated. RESULTS: Receiver Operating Characteristic curves showed a low discriminative ability of SPR and no ability to predict clinical progression in patients with MCI. Moderate correlation between SPR analysis and CSF AD biomarkers was found. CONCLUSION: The diagnostic and prognostic abilities of qEEG were low. The SPR method was superior to the visual EEG analysis. The qEEG method correlates well to CSF AD biomarkers, suggesting association with pathology in AD.

Electroencephalography Is a Good Complement to Currently Established Dementia Biomarkers.

BACKGROUND/AIMS: Dementia biomarkers that are accessible and easily applicable in nonspecialized clinical settings are urgently needed. Quantitative electroencephalography (qEEG) is a good candidate, and the statistical pattern recognition (SPR) method has recently provided promising results. We tested the diagnostic value of qEEG-SPR in comparison to cognition, structural imaging, and cerebrospinal fluid (CSF) biomarkers. METHODS: A total of 511 individuals were recruited from the multicenter NORD EEG study [141 healthy controls, 64 subjective cognitive decline, 124 mild cognitive impairment, 135 Alzheimer's disease (AD), 15 dementia with Lewy bodies/Parkinson's disease with dementia (DLB/PDD), 32 other dementias]. The EEG data were recorded in a standardized way. Structural imaging data were visually rated using scales of atrophy in the medial temporal, frontal, and posterior cortex. RESULTS: qEEG-SPR outperformed structural imaging, cognition, and CSF biomarkers in DLB/PDD diagnosis, outperformed structural imaging in AD diagnosis, and improved the differential diagnosis of AD. In addition, qEEG-SPR allowed differentiation of two clinically different AD subtypes. CONCLUSION: Adding qEEG to the diagnostic workup substantially increases the detection of AD pathology even in pre-dementia stages and improves differential diagnosis. EEG could serve as a good complement to currently established dementia biomarkers since it is cheap, noninvasive, and extensively applied outside academic centers.

Quantitative EEG Applying the Statistical Recognition Pattern Method: A Useful Tool in Dementia Diagnostic Workup.

BACKGROUND/AIM: The aim of this study was to examine the discriminatory power of quantitative EEG (qEEG) applying the statistical pattern recognition (SPR) method to separate Alzheimer's disease (AD) patients from elderly individuals without dementia and from other dementia patients. METHODS: The participants were recruited from 6 Nordic memory clinics: 372 unselected patients [mean age 71.7 years (SD 8.6), 54% women] and 146 healthy elderly individuals [mean age 66.5 years (SD 7.7), 60% women]. After a standardized and comprehensive assessment, clinical diagnoses were made according to internationally accepted criteria by at least 2 clinicians. EEGs were recorded in a standardized way and analyzed independently of the clinical diagnoses, using the SPR method. RESULTS: In receiver operating characteristic curve analyses, the qEEGs separated AD patients from healthy elderly individuals with an area under the curve (AUC) of 0.90, representing a sensitivity of 84% and a specificity of 81%. The qEEGs further separated patients with Lewy body dementia or Parkinson's disease dementia from AD patients with an AUC of 0.9, a sensitivity of 85% and a specificity of 87%. CONCLUSION: qEEG using the SPR method could be a useful tool in dementia diagnostic workup.

A novel blood test for the early detection of Alzheimer's disease.

Despite a variety of testing approaches, it is often difficult to make an accurate diagnosis of Alzheimer's disease (AD), especially at an early stage of the disease. Diagnosis is based on clinical criteria as well as exclusion of other causes of dementia but a definitive diagnosis can only be made at autopsy. We have investigated the diagnostic value of a 96-gene expression array for detection of early AD. Gene expression analysis was performed on blood RNA from a cohort of 203 probable AD and 209 cognitively healthy age matched controls. A disease classification algorithm was developed on samples from 208 individuals (AD = 103; controls = 105) and was validated in two steps using an independent initial test set (n = 74; AD = 32; controls = 42) and another second test set (n = 130; AD = 68; controls = 62). In the initial analysis, diagnostic accuracy was 71.6 ± 10.3%, with sensitivity 71.9 ± 15.6% and specificity 71.4 ± 13.7%. Essentially the same level of agreement was achieved in the two independent test sets. High agreement (24/30; 80%) between algorithm prediction and subjects with available cerebrospinal fluid biomarker was found. Assuming a clinical accuracy of 80%, calculations indicate that the agreement with underlying true pathology is in the range 85%-90%. These findings suggest that the gene expression blood test can aid in the diagnosis of mild to moderate AD, but further studies are needed to confirm these findings.

Diffusion tensor imaging (DTI) in dementia patients with frontal lobe symptoms.

BACKGROUND: Diffusion tensor imaging (DTI) is a recent MRI technique demonstrating white matter tracts in the brain. Dementia is a neurodegenerative disease and this method has been used to demonstrate the loss of axonal fibers and myelin and decrease of fiber density in this condition. PURPOSE: To study a possible correlation between frontal lobe symptoms in patients with dementia and reduced fractional anisotropy (FA) in white matter/fascicles in the frontal lobes. MATERIAL AND METHODS: The study included 23 patients with dementia and frontal lobe symptoms and 20 controls (10 Alzheimer patients without frontal lobe symptoms and 10 normal controls). Clinical tests and MRI with DTI were performed. FA in subcortical white matter of both the frontal lobes was analyzed and correlated with clinical frontal score tests. RESULTS: We found a significant correlation between frontal score results and reduction in FA in the frontal lobes. The FA in the study group was significantly lower than the FA in the control group. CONCLUSION: The present study reveals that there is a probable correlation between the extent of frontal lobe symptoms and FA in fascicles/white matter tissue in the frontal lobes.

The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) is associated with informant stress.

OBJECTIVE: To study the association between informant stress and appraisal of patients' cognitive functioning as reported by the Informant Questionnaire on Cognitive Decline in the Elderly--IQCODE. METHODS: Routinely collected data from a geriatric outpatient department (207 dyads) during the years 1995-1998 were analysed. Relative stress scale (RSS) has been categorised for possible low, intermediate and high risk of psychiatric morbidity and caregivers were combined to four groups (female and male spouses and female and male non-spouses, respectively). The relationship between IQCODE (dependent) and categorised RSS and informant groups and patient age was further studied by means of the general linear model (GLM-UNIANOVA). RESULTS: In general, spouses reported better cognitive functioning than non-spouses. There was a significant association between IQCODE and RSS (p < 0.001), and the composite variable informant group and informant gender (p < 0.001). The main effect of the interaction term RSS x informant group + informant gender was not significant. Post hoc test, however, revealed a significant effect of the interaction term RSS x female spouses (p < 0.001) on IQCODE. CONCLUSION: IQCODE is associated with informant stress. Categorisation of RSS score into groups of low, intermediate and high risk for psychiatric morbidity can be a valuable contribution to a more meaningful application of RSS in general practice.