Moyra E. Mortby

Apathy associated with neurocognitive disorders: Recent progress and future directions

Apathy is common in neurocognitive disorders (NCDs) such as Alzheimers disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities.

Prevalence of Depression in Patients With Mild Cognitive Impairment: A Systematic Review and Meta-analysis

Importance Depression is common in individuals with mild cognitive impairment (MCI) and may confer a higher likelihood of progression to dementia. Prevalence estimates of depression in those with MCI are required to guide both clinical decisions and public health policy, but published results are variable and lack precision. Objective To provide a precise estimate of the prevalence of depression in individuals with MCI and identify reasons for heterogeneity in the reported results. Data Sources A search of literature from database inception to March 2016 was performed using Medline, Embase, and PsycINFO. Hand searching of all included articles was performed, including a Google Scholar search of citations of included articles. Study Selection Articles were included if they (1) were published in English, (2) reported patients with MCI as a primary study group, (3) reported depression or depressive symptoms using a validated instrument, and (4) reported the prevalence of depression in patients with MCI. Data Extraction and Synthesis All abstracts, full-text articles, and other sources were reviewed, with data extracted in duplicate. The overall prevalence of depression in patients with MCI was pooled using a random-effects model. Heterogeneity was explored using stratification and random-effects meta-regression. Main Outcomes and Measures The prevalence of depression in patients with MCI, reported as a percentage with 95% CIs. Estimates were also stratified by population source (community-based or clinic-based sample), method of depression diagnosis (clinician-administered, informant-based, or self-report), and method of MCI diagnosis (cognitive vs global measure and amnestic vs nonamnestic). Results Of 5687 unique abstracts, 255 were selected for full-text review, and 57 studies, representing 20 892 patients, met all inclusion criteria. The overall pooled prevalence of depression in patients with MCI was 32% (95% CI, 27-37), with significant heterogeneity between estimates (I2 = 90.7%). When stratified by source, the prevalence of depression in patients with MCI in community-based samples was 25% (95% CI, 19-30) and was 40% (95% CI, 32-48) in clinic-based samples, which was significantly different (P < .001). The method used to diagnose depression did not significantly influence the prevalence estimate, nor did the criteria used for MCI diagnosis or MCI subtype. Conclusions and Relevance The prevalence of depression in patients with MCI is high. A contributor to heterogeneity in the reported literature is the source of the sample, with greater depression burden prevalent in clinic-based samples.

The Mild Behavioral Impairment Checklist (MBI-C): A Rating Scale for Neuropsychiatric Symptoms in Pre-Dementia Populations.

BACKGROUND Mild behavioral impairment (MBI) is a construct that describes the emergence at ≥50 years of age of sustained and impactful neuropsychiatric symptoms (NPS), as a precursor to cognitive decline and dementia. MBI describes NPS of any severity, which are not captured by traditional psychiatric nosology, persist for at least 6 months, and occur in advance of or in concert with mild cognitive impairment. While the detection and description of MBI has been operationalized in the International Society to Advance Alzheimers Research and Treatment - Alzheimers Association (ISTAART-AA) research diagnostic criteria, there is no instrument that accurately reflects MBI as described. OBJECTIVE To develop an instrument based on ISTAART-AA MBI criteria. METHODS Eighteen subject matter experts participated in development using a modified Delphi process. An iterative process ensured items reflected the five MBI domains of 1) decreased motivation; 2) emotional dysregulation; 3) impulse dyscontrol; 4) social inappropriateness; and 5) abnormal perception or thought content. Instrument language was developed a priori to pertain to non-demented functionally independent older adults. RESULTS We present the Mild Behavioral Impairment Checklist (MBI-C), a 34-item instrument, which can easily be completed by a patient, close informant, or clinician. CONCLUSION The MBI-C provides the first measure specifically developed to assess the MBI construct as explicitly described in the criteria. Its utility lies in MBI case detection, and monitoring the emergence of MBI symptoms and domains over time. Studies are required to determine the prognostic value of MBI for dementia development, and for predicting different dementia subtypes.

Apathy: a separate syndrome from depression in dementia? A critical review

Apathy and depression are the most prevalent neuropsychiatric symptoms in Alzheimer’s disease and mild cognitive impairment. Despite much research on apathy and depression in dementia, the nosological position of apathy as a separate syndrome from depression remains debated. This literature review provides a critical analysis of the areas of clinical manifestation, symptomatology, assessment, prevalence and neuropathology. Evidence does not provide a clear view of the nosological position of apathy in dementia for symptoms and neuropathology. However, the ambiguity of the evidence may be attributed in large part to a lack of clarity in definition and etiology, clinical criteria and assessment overlap. Given the evidence, it is concluded that the argument in favor of apathy as a separate syndrome from depression in dementia is persuasive. Reaching a consensus on the definition and nosological position of apathy within dementia is vital to provide patients and caregivers with the support they require, increase understanding of risk factors, and enable comparisons across research and practice.

High “Normal” Blood Glucose Is Associated with Decreased Brain Volume and Cognitive Performance in the 60s: The PATH through Life Study

Context Type 2 diabetes is associated with cerebral atrophy, cognitive impairment and dementia. We recently showed higher glucose levels in the normal range not to be free of adverse effects and to be associated with greater hippocampal and amygdalar atrophy in older community-dwelling individuals free of diabetes. Objective This study aimed to determine whether blood glucose levels in the normal range (<6.1 mmol/L) were associated with cerebral volumes in structures other than the hippocampus and amygdale, and whether these glucose-related regional volumes were associated with cognitive performance. Design, Setting and Participants 210 cognitively healthy individuals (68–73 years) without diabetes, glucose intolerance or metabolic syndrome were assessed in the large, community-based Personality and Total Health Through Life (PATH) study. Main Outcome Measure Baseline blood glucose levels in the normal range (3.2–6.1 mmol/l) were used to determine regional brain volumes and associated cognitive function at wave 3. Results Higher blood glucose levels in the normal range were associated with lower grey/white matter regional volumes in the frontal cortices (middle frontal gyrus, inferior frontal gyrus precentral gyrus). Moreover, identified cerebral regions were associated with poorer cognitive performance and the structure-function associations were gender specific to men. Conclusion These findings stress the need to re-evaluate what is considered as healthy blood glucose levels, and consider the role of higher normal blood glucose as a risk factor for cerebral health, cognitive function and dementia. A better lifetime management of blood glucose levels may contribute to improved cerebral and cognitive health in later life and possibly protect against dementia.

Caregiver rating bias in mild cognitive impairment and mild Alzheimer's disease: impact of caregiver burden and depression on dyadic rating discrepancy across domains

BACKGROUND Caregivers of individuals with dementia are biased in their rating of mental health measures of the care receiver. This study examines caregiver burden and depression as predictors of this bias for mild cognitive impairment and mild Alzheimers disease in different domains. METHODS The sample consisted of 202 persons: 60 with mild cognitive impairment, 41 with mild Alzheimers disease, and 101 caregivers. Discrepancy scores were calculated by subtracting the mean caregiver score from the respective mean patient score on the following assessment instruments: the Geriatric Depression Scale, Apathy Evaluation Scale, Bayer-Activities of Daily Living Scale, and Quality of Life-AD scale. Caregiver burden and depression were assessed by the Zarit Burden Interview and the Center for Epidemiologic Studies Depression Scale. RESULTS Intraclass correlation coefficients were low for apathy (0.38), daily functioning (0.38), and quality of life (0.30) and moderate for depression (0.49). These domains showed negative rating discrepancies, which indicates caregiver rating bias for all four domains. Regression analyses revealed that caregiver burden significantly contributed to explaining these discrepancies in the domains apathy, daily functioning, and quality of life. CONCLUSION Caregiver rating bias can be attributed to caregiver burden. When caregiver burden is present, data based on caregiver ratings should therefore be interpreted with caution.

Evaluation of a research diagnostic algorithm for DSM-5 neurocognitive disorders in a population-based cohort of older adults

BackgroundThere is little information on the application and impact of revised criteria for diagnosing dementia and mild cognitive impairment (MCI), now termed major and mild neurocognitive disorders (NCDs) in the DSM-5. We evaluate a psychometric algorithm for diagnosing DSM-5 NCDs in a community-dwelling sample, and characterize the neuropsychological and functional profile of expert-diagnosed DSM-5 NCDs relative to DSM-IV dementia and International Working Group criteria for MCI.MethodsA population-based sample of 1644 adults aged 72–78 years was assessed. Algorithmic diagnostic criteria used detailed neuropsychological data, medical history, longitudinal cognitive performance, and informant interview. Those meeting all criteria for at least one diagnosis had data reviewed by a neurologist (expert diagnosis) who achieved consensus with a psychiatrist for complex cases.ResultsThe algorithm accurately classified DSM-5 major NCD (area under the curve (AUC) = 0.95, 95% confidence interval (CI) 0.92–0.97), DSM-IV dementia (AUC = 0.91, 95% CI 0.85–0.97), DSM-5 mild NCD (AUC = 0.75, 95% CI 0.70–0.80), and MCI (AUC = 0.76, 95% CI 0.72–0.81) when compared to expert diagnosis. Expert diagnosis of dementia using DSM-5 criteria overlapped with 90% of DSM-IV dementia cases, but resulted in a 127% increase in diagnosis relative to DSM-IV. Additional cases had less severe memory, language impairment, and instrumental activities of daily living (IADL) impairments compared to cases meeting DSM-IV criteria for dementia. DSM-5 mild NCD overlapped with 83% of MCI cases and resulted in a 19% increase in diagnosis. These additional cases had a subtly different neurocognitive profile to MCI cases, including poorer social cognition.ConclusionDSM-5 NCD criteria can be operationalized in a psychometric algorithm in a population setting. Expert diagnosis using DSM-5 NCD criteria captured most cases with DSM-IV dementia and MCI in our sample, but included many additional cases suggesting that DSM-5 criteria are broader in their categorization.

Using sulcal and gyral measures of brain structure to investigate benefits of an active lifestyle

BACKGROUND Physical activity is associated with brain and cognitive health in ageing. Higher levels of physical activity are linked to larger cerebral volumes, lower rates of atrophy, better cognitive function and a lower risk of cognitive decline and dementia. Neuroimaging studies have traditionally focused on volumetric brain tissue measures to test associations between factors of interest (e.g. physical activity) and brain structure. However, cortical sulci may provide additional information to these more standard measures. METHOD Associations between physical activity, brain structure, and cognition were investigated in a large, community-based sample of cognitively healthy individuals (N=317) using both sulcal and volumetric measures. RESULTS Physical activity was associated with narrower width of the Left Superior Frontal Sulcus and the Right Central Sulcus, while volumetric measures showed no association with physical activity. In addition, Left Superior Frontal sulcal width was associated with processing speed and executive function. DISCUSSION These findings suggest sulcal measures may be a sensitive index of physical activity related to cerebral health and cognitive function in healthy older individuals. Further research is required to confirm these findings and to examine how sulcal measures may be most effectively used in neuroimaging.

Blood Pressure, Brain Structure, and Cognition: Opposite Associations in Men and Women

BACKGROUND Research on associations between blood pressure, brain structure, and cognitive function has produced somewhat inconsistent results. In part, this may be due to differences in age ranges studied and because of sex differences in physiology and/or exposure to risk factors, which may lead to different time course or patterns in cardiovascular disease progression. The aim of this study was to investigate the impact of sex on associations between blood pressure, regional cerebral volumes, and cognitive function in older individuals. METHODS In this cohort study, brachial blood pressure was measured twice at rest in 266 community-based individuals free of dementia aged 68-73 years who had also undergone a brain scan and a neuropsychological assessment. Associations between mean blood pressure (MAP), regional brain volumes, and cognition were investigated with voxel-wise regression analyses. RESULTS Positive associations between MAP and regional volumes were detected in men, whereas negative associations were found in women. Similarly, there were sex differences in the brain-volume cognition relationship, with a positive relationship between regional brain volumes associated with MAP in men and a negative relationship in women. CONCLUSIONS In this cohort of older individuals, higher MAP was associated with larger regional volume and better cognition in men, whereas opposite findings were demonstrated in women. These effects may be due to different lifetime risk exposure or because of physiological differences between men and women. Future studies investigating the relationship between blood pressure and brain structure or cognitive function should evaluate the potential for differential sex effects.

Midlife motivational abilities predict apathy and depression in Alzheimer disease: The aging, demographics, and memory study

Apathy and depression are the most common neuropsychiatric symptoms in mild cognitive impairment (MCI) and Alzheimer disease (AD). This study was the first to explore midlife motivational abilities as a predictor of the progression of apathy and depression in MCI and AD. It used a subsample of the Aging, Demographics, and Memory Study (N = 137). Participants, aged over 70, were categorized according to baseline clinical diagnosis (normal cognition, MCI, or AD). Assessments were conducted at an 18-month interval. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. Midlife motivational abilities were estimated on the basis of the main occupation using the Occupational Information Network (O*NET) database, which provides detailed information on worker abilities. Repeated measures analysis of covariance was used. Apathy and depression were found to be particularly high in participants with AD and high motivational abilities. Apathy, but not depression, increased over time in those with AD and high motivational abilities. It would appear that holding on to unattainable goals with strong motivational efforts when faced with severe cognitive loss might lead to unproductive persistence, depressive reaction, and more apathetic behavior.