Decision Making and the Brain: Neurologists' View

The article reflects the fact, that concepts like decision making and free will have entered the field of cognitive neuroscience towards the end of 20th century. It gives an overview of brain structures involved in decision making and the concept of free will; and presenting the results of clinical observations and new methods (functional neuroimaging, electrophysiology) it postulates possible mechanisms of these processes. We give a review of the neuroanatomy, specially discussing those parts of the brain important to the present topic, because the process of decision making is dependent on deep subcortical as well as superficial cortical structures. Dopamine has a central role in the in process of reward related behaviour and hedonism. A list of brain structures, related to dopamine action, is also given. The article especially concentrates on the Single Photon Emission Computer Tomography studies in patients with Parkinson's disease (neuroimaging), as well as to the studies concerning the Readiness Potential and Endogeneous Potential P300 (electrophysiology). In the end, we discuss the volition, whose functional anatomy overlaps with the functional anatomy of free will and decision making processes.cognitive neuroscience, brain, decision making, free will, electrophysiology, functional imaging, dopamine

Cerebrospinal Fluid Alzheimer Markers in Depressed Elderly Subjects with and without Alzheimer's Disease

Depression and Alzheimer’s disease (AD) are among the most common clinical diagnosis in older people. The relation between depression and AD is complex: depression has been shown to be a risk factor, prodromal symptom and a consequence of AD. Increased understanding of the underlying mechanisms of depression in AD may lead to early detection and differential diagnosis, and is crucial for development of novel and mechanism-based treatments. The first two studies of this doctoral thesis are exploring the associations between depressive symptoms and biomarkers of amyloid deposition and neuronal injury in patients with subjective cognitive impairment (SCI), mild cognitive impairment (MCI) and AD. The aims of the third study were to describe the use of antidepressants in patients with dementia and to explore the association between mortality risk and the use of antidepressants 3 years before the dementia diagnosis. CAIDE Dementia Risk Score is taking into account midlife risk and protective factors; age, educational level, gender, systolic blood pressure, body mass index, cholesterol level and physical activity and APOE genotyping, and can predict dementia over 20 years. The last study was focused on exploring the associations between CAIDE Dementia Risk Score and biomarkers of amyloid deposition, neuronal injury and small vessel pathology in SCI and MCI patients. Additionally we explored the capacity of CAIDE Dementia Risk Score to predict dementia in a memory clinic population. Data were obtained from Memory Clinic Karolinska University Hospital Huddinge Sweden (Study I, II and IV). In study III, two large national registries were merged: the Swedish Dementia Registry (SveDem) and the Swedish Prescribed Drug Register. In study I, analysis of the three different cerebrospinal fluid biomarkers; amyloid beta (CSF Aβ), total-tau (CSF t-tau), and phosphorylated-tau did not support the hypothesis that more severe amyloid or tau pathologies are associated with more severe depressive symptoms. In contrast, SCI and AD patients with depressive symptoms tended to have lower CSF p-tau levels and, in particular, lower CSF t-tau levels than those without depression, indicating less severe neuronal injury. In study II, we used two different analysis methods of MRI to measure medial temporal lobe atrophy and hippocampus volume. Using manual tracing of the hippocampi we found smaller left hippocampus volume in SCI patients with depressive symptoms compared to those without depressive symptoms. In contrast, AD patients with depressive symptoms had less medial temporal lobe atrophy compared with those without depressive symptoms. In study III, 20,050 patients with incident dementia diagnosed in memory clinics and registered in SveDem were included. Information on the total number of medication and all antidepressants dispensed at the time of dementia diagnosis and at the first, the second and the third year prior to dementia diagnosis was obtained from the Swedish Prescribed Drug Register. During a median follow up of 2 years, 5168 (25.8%) dementia patients died. At the time of dementia diagnosis, 5,004 (25.0%) patients were on antidepressant treatment. Use of antidepressant treatment for 3 consecutive years prior to a dementia diagnosis was associated with a lower mortality risk for all dementia disorders in general and particularly in AD. In study IV, a higher CAIDE Dementia Risk Score was associated with higher CSF t-tau levels, more severe medial temporal lobe atrophy and more severe white matter changes. For the CAIDE score including APOE, a score above 9 points was associated with lower CSF Aβ, more severe medial temporal lobe atrophy and more severe white matter changes. CAIDE Dementia Risk Score (version with APOE) performed better at predicting AD compared with CAIDE Dementia Risk Score without APOE. Conclusion: We found that depressive symptoms in patients with AD and SCI are not associated with more amyloid deposition nor more neuronal injury compared with AD and SCI patients without depressive symptoms. Thus our results are consistent with the hypothesis that the mechanisms underlying depression differ between older people with and without AD. Our results have shown that use of antidepressants in prodromal AD stages is associated with a lower mortality risk. Further longitudinal studies are needed to better understand the associations between the use of antidepressants and mortality risk in dementia

Feasibility and usability of remote monitoring in Alzheimer’s disease

Introduction: Remote monitoring technologies (RMTs) can measure cognitive and functional decline objectively at-home, and offer opportunities to measure passively and continuously, possibly improving sensitivity and reducing participant burden in clinical trials. However, there is skepticism that age and cognitive or functional impairment may render participants unable or unwilling to comply with complex RMT protocols. We therefore assessed the feasibility and usability of a complex RMT protocol in all syndromic stages of Alzheimer’s disease and in healthy control participants.Methods: For 8 weeks, participants (N=229) used two activity trackers, two interactive apps with either daily or weekly cognitive tasks, and optionally a wearable camera. A subset of participants participated in a 4-week sub-study (N=45) using fixed at-home sensors, a wearable EEG sleep headband and a driving performance device. Feasibility was assessed by evaluating compliance and drop-out rates. Usability was assessed by problem rates (e.g., understanding instructions, discomfort, forgetting to use the RMT or technical problems) as discussed during bi-weekly semi-structured interviews.Results: Most problems were found for the active apps and EEG sleep headband. Problem rates increased and compliance rates decreased with disease severity, but the study remained feasible.Conclusions: This study shows that a highly complex RMT protocol is feasible, even in a mild-to-moderate AD population, encouraging other researchers to use RMTs in their study designs. We recommend evaluating the design of individual devices carefully before finalizing study protocols, considering RMTs which allow for real-time compliance monitoring, and engaging the partners of study participants in the research.<br/

Cost of diagnosing and treating cognitive complaints : One-year cost-evaluation study in a patient cohort from a Slovenian memory clinic

Introduction: Dementias present a global health challenge and give rise to significant economic costs. This study aims to evaluate the economic impact of one-year outpatient healthcare, nursing home, and formal and informal home help costs for all patients referred to the Centre for Cognitive Impairments at the Department of Neurology, Ljubljana University Medical Centre, Slovenia. Methods: Data was acquired retrospectively from physicians' records and the costs for 2015 were calculated. Total costs were estimated by means of a bottom-up calculation of outpatient visits, diagnostic examinations and anti-dementia medication. In a subgroup of 120 patients with dementia, the Resource Utilization in Dementia questionnaire was used to estimate formal and informal care costs. Results: A total of 720 patients visited the memory clinic in 2015. Diagnosis at first visit was subjective cognitive or mild cognitive impairment (SCI/ MCI) for 322 patients, dementia for 258 patients, and psychiatric or other disorders for 140 patients. The average annual cost per patient was EUR 578. It was highest for patients with dementia (EUR 751), EUR 550 for patients with SCI/MCI, and lowest for patients with psychiatric and other disorders (EUR 324). Monthly informal and social care costs were between EUR 1,037 and EUR 3,369, depending on the methodology used. Conclusion: The cost of diagnosing a cognitive disorder depends on how extensive the diagnosis is. With an estimated prevalence of 34,137 persons with dementia in Slovenia, basic diagnostic investigations incur costs of approximately EUR 7 million. Direct medical costs represent a smaller portion of total dementia costs; this is because annual costs for formal and informal home help are estimated at EUR 265 million and nursing home placements at EUR 105 million

Subjective cognitive impairment subjects in our clinical practice

BACKGROUND: The clinical challenge in subjective cognitive impairment (SCI) is to identify which individuals will present cognitive decline. We created a statistical model to determine which variables contribute to SCI and mild cognitive impairment (MCI) versus Alzheimer's disease (AD) diagnoses. METHODS: A total of 993 subjects diagnosed at a memory clinic (2007-2009) were included retrospectively: 433 with SCI, 373 with MCI and 187 with AD. Descriptive statistics were provided. A logistic regression model analyzed the likelihood of SCI and MCI patients being diagnosed with AD, using age, gender, Mini-Mental State Examination score, the ratio of β-amyloid 42 divided by total tau, and phosphorylated tau as independent variables. RESULTS: The SCI subjects were younger (57.8 ± 8 years) than the MCI (64.2 ± 10.6 years) and AD subjects (70.1 ± 9.7 years). They were more educated, had less medial temporal lobe atrophy (MTA) and frequently normal cerebrospinal fluid biomarkers. Apolipoprotein E4/E4 homozygotes and apolipoprotein E3/E4 heterozygotes were significantly less frequent in the SCI group (6 and 36%) than in the AD group (28 and 51%). Within the regression model, cardiovascular risk factors, confluent white matter lesions, MTA and central atrophy increased the AD likelihood for SCI subjects. CONCLUSIONS: SCI patients form a distinct group. In our model, factors suggesting cardiovascular risk, MTA and central atrophy increased the AD likelihood for SCI subjects

CAIDE Dementia Risk Score and biomarkers of neurodegeneration in memory clinic patients without dementia

The aim of this study was to explore cross-sectional associations between Cardiovascular Risk Factors, Aging and Dementia Study (CAIDE) Dementia Risk Score and dementia-related cerebrospinal fluid and neuroimaging biomarkers in 724 patients without dementia from the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden. We additionally evaluated the score's capacity to predict dementia. Two risk score versions were calculated: one including age, gender, obesity, hyperlipidemia, and hypertension; and one additionally including apolipoprotein E (APOE) ε4 carrier status. Cerebrospinal fluid was analyzed for amyloid β (Aβ), total tau, and phosphorylated tau. Visual assessments of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal subscale, and Fazekas scale for white matter changes (WMC) were performed. Higher CAIDE Dementia Risk Score (version without APOE) was significantly associated with higher total tau, more severe MTA, WMC, and global cortical atrophy-frontal subscale. Higher CAIDE Dementia Risk Score (version with APOE) was associated with reduced Aβ, more severe MTA, and WMC. CAIDE Dementia Risk Score version with APOE seemed to predict dementia better in this memory clinic population with short follow-up than the version without APOE

Mortality after Ischemic Stroke in Patients with Alzheimer's Disease Dementia and Other Dementia Disorders

Background: Stroke and dementia are interrelated diseases and risk for both increases with age. Even though stroke incidence and age-standardized death rates have decreased due to prevention of stroke risk factors, increased utilization of reperfusion therapies, and other changes in healthcare, the absolute numbers are increasing due to population growth and aging. Objective: To analyze predictors of death after stroke in patients with dementia and investigate possible time and treatment trends. Methods: A national longitudinal cohort study 2007-2017 using Swedish national registries. We compared 12,629 ischemic stroke events in patients with dementia with matched 57,954 stroke events in non-dementia controls in different aspects of patient care and mortality. Relationship between dementia status and dementia type (Alzheimer's disease and mixed dementia, vascular dementia, other dementias) and death was analyzed using Cox regressions. Results: Differences in receiving intravenous thrombolysis between patients with and without dementia disappeared after the year 2015 (administered to 11.1% dementia versus 12.3% non-dementia patients, p = 0.117). One year after stroke, nearly 50% dementia and 30% non-dementia patients had died. After adjustment for demographics, mobility, nursing home placement, and comorbidity index, dementia was an independent predictor of death compared with non-dementia patients (HR 1.26 [1.23-1.29]). Conclusion: Dementia before ischemic stroke is an independent predictor of death. Over time, early and delayed mortality in patients with dementia remained increased, regardless of dementia type. Patients with≤80 years with prior Alzheimer's disease or mixed dementia had higher mortality rates after stroke compared to patients with prior vascular dementia