Dr Moyra Mortby


Special Issue on mild behavioral impairment and non-cognitive prodromes to dementia.

Mortby ME, Lyketsos CG, Geda YE, Ismail Z

This Special Issue provides a systematic examination of the neuropsychiatric symptoms (NPS) and non-cognitive prodromes of dementia, with an eye toward validating the construct of mild behavioral impairment (MBI).

Dementia clinical trial implications of mild behavioral impairment.

Mortby ME, Black SE, Gauthier S, Miller D, Porsteinsson A, Smith EE, Ismail Z

The World Alzheimer Report 2016 estimated that 47 million people are living with dementia worldwide (Alzheimer's Disease International, 2016). In the inaugural World Health Organization Ministerial Conference on Global Action against Dementia, six of the top ten research priorities were focused on prevention, identification, and reduction of dementia risk, and on delivery and quality of care for people with dementia and their carers (Shah et al., 2016). While the Lancet Neurology Commission has suggested that even minor advances to delay progression or ameliorate symptoms might have substantial financial and societal benefits (Winblad et al., 2016), advances have been slow.

Prevalence estimates of mild behavioral impairment in a population-based sample of pre-dementia states and cognitively healthy older adults.

Mortby ME, Ismail Z, Anstey KJ

This study presents the first population-based prevalence estimates for MBI using the recently published ISTAART-AA diagnostic criteria. Findings indicate relatively high prevalence of MBI in pre-dementia clinical states and amongst cognitively healthy older adults. Findings were gender-specific, with MBI affecting more men than women. Knowing the estimates of these symptoms in the population is essential for understanding and differentiating the very early development of clinical disorders.

Affective and emotional dysregulation as pre-dementia risk markers: exploring the mild behavioral impairment symptoms of depression, anxiety, irritability, and euphoria.

Ismail Z, Gatchel J, Bateman DR, Barcelos-Ferreira R, Chantillon M, Jaeger J, Donovan NJ, Mortby ME

Affective symptoms are of prognostic utility, but interventions to prevent dementia syndromes are limited. Trials need to assess interventions targeting known dementia pathology, toward novel pathology, as well as using psychiatric medications. Research focusing explicitly on later life onset symptomatology will improve our understanding of the neurobiology of NPS and neurodegeneration, enrich the study sample, and inform observational and clinical trial design for prevention and treatment strategies.

Prevalence of mild behavioral impairment in mild cognitive impairment and subjective cognitive decline, and its association with caregiver burden.

Sheikh F, Ismail Z, Mortby ME, Barber P, Cieslak A, Fischer K, Granger R, Hogan DB, Mackie A, Maxwell CJ, Menon B, Mueller P, Patry D, Pearson D, Quickfall J, Sajobi T, Tse E, Wang M, Smith EE,

MBI was common in memory clinic patients without dementia and was associated with greater caregiver burden. These data show that MBI is a common and clinically relevant syndrome.

Differential associations between sensory loss and neuropsychiatric symptoms in adults with and without a neurocognitive disorder.

Kiely KM, Mortby ME, Anstey KJ

The extent to which this association is the result of underlying neuropathology, unmet need, or interpersonal factors is unclear. These findings have significant implications for dementia care settings, including hospitals and respite care, as patients with sensory loss are at increased risk of neuropsychiatric symptoms and may require additional psychosocial support. Interventions to manage sensory loss and reduce the impact of sensory limitations on neuropsychiatric symptoms are needed.

Neuropsychiatric Symptoms and Cognitive Impairment: Understanding the Importance of Co-Morbid Symptoms.

Mortby ME, Burns R, Eramudugolla R, Ismail Z, Anstey KJ

To characterize the prevalence of NPS and explore the clinical implications of co-morbid symptom presentation. Our findings confirm previous reports on the prevalence of NPS in community-based samples and are consistent with the profiles of NPS domain characteristics of MCI and dementia. Number of co-morbid NPS and not symptom clusters are associated with increased risk of dementia. Understanding such patterns will help inform our understanding of mild behavioral disorders and assist with clinical assessment.

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

Eramudugolla R, Mortby ME, Sachdev P, Meslin C, Kumar R, Anstey KJ

DSM-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.

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

Ismail Z, Agüera-Ortiz L, Brodaty H, Cieslak A, Cummings J, Fischer CE, Gauthier S, Geda YE, Herrmann N, Kanji J, Lanctôt KL, Miller DS, Mortby ME, Onyike CU, Rosenberg PB, Smith EE, Smith GS, Sultzer DL, Lyketsos C,

To develop an instrument based on ISTAART-AA MBI criteria. 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.

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

Ismail Z, Elbayoumi H, Fischer CE, Hogan DB, Millikin CP, Schweizer T, Mortby ME, Smith EE, Patten SB, Fiest KM

To provide a precise estimate of the prevalence of depression in individuals with MCI and identify reasons for heterogeneity in the reported results. 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.

Apathy associated with neurocognitive disorders: Recent progress and future directions.

Lanctôt KL, Agüera-Ortiz L, Brodaty H, Francis PT, Geda YE, Ismail Z, Marshall GA, Mortby ME, Onyike CU, Padala PR, Politis AM, Rosenberg PB, Siegel E, Sultzer DL, Abraham EH

Blood pressure, brain structure, and cognition: opposite associations in men and women.

Cherbuin N, Mortby ME, Janke AL, Sachdev PS, Abhayaratna WP, Anstey KJ

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.

Relating education, brain structure, and cognition: the role of cardiovascular disease risk factors.

Mortby ME, Burns R, Janke AL, Sachdev PS, Anstey KJ, Cherbuin N

The protective effect of education on cognitive and brain health is well established. While the direct effects of individual cardiovascular disease (CVD) risk factors (i.e., hypertension, smoking, diabetes, and obesity) on cerebral structure have been investigated, little is understood about the possible interaction between the protective effect of education and the deleterious effects of CVD risk factors in predicting brain ageing and cognition. Using data from the PATH Through Life study (N = 266), we investigated the protective effect of education on cerebral structure and function and tested a possible mediating role of CVD risk factors. Higher education was associated with larger regional grey/white matter volumes in the prefrontal cortex in men only. The association between education and cognition was mediated by brain volumes but only for grey matter and only in relation to information processing speed. CVD risk factors did not mediate the association between regional volumes and cognition. This study provides additional evidence in support for a protective effect of education on cerebral structures and cognition. However, it does not provide support for a mediating role of CVD risk factors in these associations.

Depressive symptoms in later life: differential impact of social support and motivational processes on depression in individuals with and without cognitive impairment.

Fankhauser S, Drobetz R, Mortby M, Maercker A, Forstmeier S

This study investigates the role of a motivational process based on a composite of four subcomponents (self-efficacy, decision regulation, activation regulation and motivation regulation), as a mediator of the relationship between social support and depression assessed with the Geriatric Depression Scale in cognitively impaired and unimpaired individuals. Participants were 229 adults with a mean age of 74 years (range: 52-94 years). The sample comprised 64 participants diagnosed with mild cognitive impairment (MCI), 47 participants diagnosed with early-stage Alzheimer's disease (AD), and a group of 118 participants without any cognitive impairment. In this cross-sectional study, bivariate correlations and linear regression models were used to assess the association between the predictor variables and depression. Linear regression models were controlled for age, gender, education, cognitive status, cognitive impairment and activities. In the total sample, social support ( = -0.15,  < 0.05) and motivational processes ( = -0.41,  < 0.001) were significantly associated with depression; the impact of social support was mediated by motivational processes. While motivational processes were associated with depression in all three groups (no impairment:  = -0.61,  < 0.001; MCI:  = -0.28,  < 0.05; early AD:  = -0.30,  < 0.06), social support lost significance (no impairment:  = -0.36,  < 0.001; MCI:  = 0.07,  = 0.59; early AD:  = -0.08,  = 0.62). Based on these findings, it can be argued that the impact of social support on depressive symptoms is attenuated by cerebral deterioration in cognitively impaired individuals, while motivational processes remain relevant.

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

Lamont AJ, Mortby ME, Anstey KJ, Sachdev PS, Cherbuin N

High "normal" blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the PATH through life study.

Mortby ME, Janke AL, Anstey KJ, Sachdev PS, Cherbuin N

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. 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.

Evaluation and management of the non-motor features of Parkinson's disease.

Wishart S, Macphee GJ

Parkinson's disease (PD) is traditionally viewed as a motor disorder with a characteristic triad of tremor, rigidity and bradykinesia. There is now increasing awareness that PD is a complex systemic disorder with many nonmotor symptoms (NMS) which include autonomic dysfunction, sleep disorders, sensory and neuropsychiatric features. NMS become more common in severity and frequency with advancing disease when neuropsychiatric features such as cognitive impairment and psychosis dominate the clinical picture. NMS are strongly correlated with quality of life for patients and their families as well as institutional care placement. Despite their importance, NMS are poorly recognized by clinicians and often undeclared by patients. Use of a validated screening tool NMSQuest followed by specific symptom assessment instruments strengthens the recognition and holistic management of NMS in PD. Some NMS such as mood disturbance, anxiety, pain and insomnia may be improved by optimization of dopaminergic therapy. Conversely, psychosis, excess daytime somnolence or impulse control disorder (ICD) may be triggered by dopaminergic drugs. Other NMS such as dementia and severe depression may be unresponsive to dopaminergic treatment and may reflect perturbations in cholinergic, serotonergic or noradrenergic neurotransmitter function. These symptoms are more challenging to manage but may be ameliorated to some extent by agents such as acetylcholinesterase inhibitor or antidepressant drugs. This contribution reviews the evidence for the evaluation and management of key NMS in PD (apathy, anxiety, depression, psychosis, dementia, ICD, sleep disturbance, autonomic dysfunction, pain) and highlights the urgent need for both novel therapies and more controlled trials for current therapeutic strategies.

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

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

Mortby ME, Maercker A, Forstmeier S

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.

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

Mortby ME, Maercker A, Forstmeier S

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.