Shellie-Anne T. Levy and Glenn E. Smith
Dementia, also now known as major neurocognitive disorder, is a syndrome involving decline in two or more areas of cognitive function sufficient to disrupt a person’s daily function. Mild cognitive impairment (MCI), also known as minor neurocognitive disorder, represents a syndrome on the continuum of cognitive decline that is a stage prior to development of functional deficits. It involves decline in one or more areas of cognitive function with independence in instrumental activities of daily living, even though they may require greater effort or compensation on the part of the individual. Neuropsychological assessment of cognition and behavior provides the most powerful biomarkers for MCI and dementia syndromes associated with neurodegenerative diseases. Discrete cognitive and behavioral patterns that occur early in the course of cognitive decline aids in differential clinical diagnosis. Additionally, all diagnostic schemes for dementia syndromes include criteria that require the appraisal of functional status, which tests an individual’s capacity to engage in decision making and carry out activities of daily living independently. Methods for assessing functional status have historically had poor reliability and validity. Nevertheless, in a clinical setting, neuropsychologists rely on a combination of self-report, collateral informants, caregiver questionnaires, and objective performance-based measures to better assess functional status. Revisions to clinical criteria for dementia reflect the adoption of new research diagnostic criteria for neurodegenerative diseases, largely driven by the National Institutes of Aging (NIA) and the Alzheimer’s Association 2011 research criteria for Alzheimer’s disease (AD). The new approach differentiates the syndromic presentations common to most neurodegenerative diseases from the etiologies (AD, LBD, VaD, etc.) based on biomarkers. In the preclinical stage, biomarker abnormalities are present years before clinical symptom manifestation. In mild cognitive impairment stage, there is a report/concern for cognitive change by the patient, informant, or clinician. There is objective cognitive decline from estimated premorbid functioning and preserved independence in functional abilities. In the dementia stage, in the context of impaired functional status, there may be prominent cognitive and behavioral symptoms that may involve impairment in memory, executive function, visuospatial functioning, and language, as well as changes in personality and behavior. The most common dementias are AD, dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VaD). All can follow a trajectory of cognitive decline similar to the aforementioned stages and are associated with neuropathogenic mechanisms that may or may not be distinctive for a particular syndrome. Briefly, Alzheimer’s dementia is associated with accumulation of amyloid plaques and tau neurofibrillary tangles. Lewy body dementias (i.e., Parkinson’s disease dementia and DLB) are characterized by Lewy bodies (alpha-synuclein aggregates) and Lewy neurites in the brainstem, limbic system, and cortical regions; DLB is also associated with diffuse amyloid plaques. Frontotemporal dementia is a conglomerate of syndromes that may overlap and include behavioral variant FTD, semantic dementia, and primary progressive aphasia (PPA). FTD dementia syndromes are marked by frontotemporal lobar degeneration (FTLD) caused by pathophysiological processes involving FTLD-tau, FTLD-TDP, FTLD-FUS, or their combination, as well as beta amyloid. Lastly, vascular dementia is associated with cerebrovascular disease that can include large artery occlusions, microinfarcts, brain hemorrhages, and silent brain infarcts; comorbid AD pathology may lower the threshold for dementia conversion. There is an emerging shift in the field toward exploring prevention strategies for dementia. Given the lack of precision in our language regarding the distinction between dementia syndromes and etiologies, we can reallocate some of our efforts to preventing dementia more broadly rather than intervening on a certain pathology. Research already supports that many individuals have biomarker evidence of brain pathology without showing cognitive impairment or even sufficient levels of pathology in the brain to warrant a diagnosis without ever displaying the clinical syndrome of dementia. That said, building cognitive reserve or resilience through lifestyle and behavioral factors may slow the rate of cognitive decline and prevent the risk of a future dementia epidemic.
Anthony Randal McIntosh
Brain organization can be measured across multiple spatial and temporal scales where each scale affects the other in the emergent functions that are known as cognition. As a complex adaptive system, the interplay of these scales in the brain represents the information that ultimately supports what one thinks and does. The dynamics of these multiscale operations can be quantified with measures of complexity, which are sensitive to the balance between information that is coded in local cell populations and that is captured in the network interactions between populations. This local versus global balance has its foundation in the structural connectivity of the brain, which is then realized through the dynamics of cell populations and their ensuing interactions with other populations. Considering brain function and cognition in this way enables a different perspective on the changes in cognitive function in aging.
Changes in brain signal complexity from childhood to adulthood were assessed in two independent studies. Both showed that maturation is accompanied by an overall increase in signal complexity, which also correlated with more stable and accurate cognitive performance. There was some suggestion that the maximal change occurs in medial posterior cortical areas, which have been considered “network hubs” of the brain. In extending to the study of healthy aging, a scale-dependent change in brain complexity was observed across three independent studies. Healthy aging brings a shift in local and global balance, where more information is coded in local dynamics and less in global interactions. This balance is associated with better cognitive performance and, interestingly, in a more active lifestyle. It also seems that the lack of this shift in local and global balance is predictive of worse cognitive performance and potentially predictive of additional decline indicative of dementia.
Nadeeka N. Dissanayaka
Progressive neurological disorders are incurable disorders with gradual deterioration and impacting patients for life. Two common progressive neurological disorders found in late life are Parkinson’s disease (PD) and motor neuron disease (MND). Psychological complications such as depression and anxiety are prevalent in people living with PD and MND, yet they are underdiagnosed and poorly treated.
PD is classified a Movement Disorder and predominantly characterized by motor symptoms such as tremor, bradykinesia, gait problems and postural instability; however, neuropsychiatric complications such as anxiety and depression are common and contribute poorly to quality of life, even more so than motor disability. The average prevalence of depression in PD suggest 35% and anxiety in PD reports 31%. Depression and anxiety often coexist. Symptoms of depression and anxiety overlap with symptoms of PD, making it difficult to recognize. In PD, daily fluctuations in anxiety and mood disturbances are observed with clear synchronized relationships to wearing off of PD medication in some individuals. Such unique characteristics must be addressed when treating PD depression and anxiety. There is an increase in the evidence base for psychotherapeutic approaches such as cognitive behavior therapy to treat depression and anxiety in PD.
Motor neuron disease (MND) is classified a neuromuscular disease and is characterized by progressive degeneration of upper and lower motor neurons is the primary characteristic of MND. The most common form of MND is Amyotrophic lateral sclerosis (ALS) and the terms ALS and MND are simultaneously used in the literature. Given the short life expectancy (average 4 years), rapid deterioration, paralysis, nonmotor dysfunctions, and resulting incapacity, psychological factors clearly play a major role in MND. Depression and suicide are common psychological concerns in persons with MND. While there is an ALS-specific instrument to assess depression, evaluation of anxiety is poorly studied; although emerging studies suggesting that anxiety is highly prevalent in MND. Unfortunately, there is no substantial evidence-base for the treatment of anxiety and depression in MND.
Caregivers play a major role in the management of progressive neurological diseases. Therefore, evaluating caregiver burden and caregiver psychological health are essential to improve quality of care provided to the patient, as well as to improve quality of life for carers. In progressive neurological diseases, caregiving is often provided by family members and spouses, with professional care at advanced disease. Psychological interventions for PD carers addressing unique characteristics of PD and care needs is required. Heterogeneous clinical features, rapid functional decline, and short trajectory of MND suggest a multidisciplinary framework of carer services including psychological interventions to mitigate MND. A Supportive Care Needs Framework has been recently proposed encompassing practical, informational, social, psychological, physical, emotional, and spiritual needs of both MND patients and carers.
David Bunce and Sarah Bauermeister
Intraindividual variability in the present context refers to the moment-to-moment variation in attentional or executive engagement over a given time period. Typically, it is measured using the response latencies collected across the trials of a behavioral neurocognitive task. In aging research, the measure has received a lot of recent interest as it may provide important insights into age-related cognitive decline and neuropathology as well as having potential as a neurocognitive assessment tool in healthcare settings. In the present chapter, we begin by reviewing the key empirical findings relating to age and intraindividual variability. Here, research shows that intraindividual variability increases with age and predicts a range of age-related outcomes including gait impairment, falls and errors more broadly, mild cognitive impairment, dementia, and mortality. Brain imaging research suggests that greater variability is associated with age-related or neuropathological changes to a frontal–cingulate–parietal network and that white matter compromise and dopamine depletion may be key underlying mechanisms. We then consider the cognitive and neurobiological theoretical underpinnings of the construct before providing a description of the various methods and metrics that have been used to compute measures of variability – reaction time cut-offs, raw and residualized intraindividual standard deviations, coefficient of variation, ex-Gaussian curve and fast Fourier transformation. A further section considers the range of neurocognitive tasks that have been used to assess intraindividual variability. Broadly, these tasks can be classified on a continuum of cognitive demands as psychomotor, executive control or higher-order cognitive tasks (e.g., episodic memory). Finally, we provide some pointers concerning the pressing issues that future research needs to address in the area. We conclude that the existing body of theoretical and empirical work underlines the potential of intraindividual reaction time variability measures as additions to the neuropsychological test batteries that are used in the early detection of a range of age-related neurocognitive disorders in healthcare settings.
David J. Madden and Zachary A. Monge
Age-related decline occurs in several aspects of fluid, speed-dependent cognition, particularly those related to attention. Empirical research on visual attention has determined that attention-related effects occur across a range of information processing components, including the sensory registration of features, selection of information from working memory, controlling motor responses, and coordinating multiple perceptual and cognitive tasks. Thus, attention is a multifaceted construct that is relevant at virtually all stages of object identification. A fundamental theme of attentional functioning is the interaction between the bottom-up salience of visual features and top-down allocation of processing based on the observer’s goals. An underlying age-related slowing is prominent throughout visual processing stages, which in turn contributes to age-related decline in some aspects of attention, such as the inhibition of irrelevant information and the coordination of multiple tasks. However, some age-related preservation of attentional functioning is also evident, particularly the top-down allocation of attention. Neuroimaging research has identified networks of frontal and parietal brain regions relevant for top-down and bottom-up attentional processing. Disconnection among these networks contributes to an age-related decline in attention, but preservation and perhaps even increased patterns of functional brain activation and connectivity also contribute to preserved attentional functioning.
Benjamin Boller and Sylvie Belleville
Individuals with mild cognitive impairment (MCI) experience cognitive difficulties and many find themselves in a transitional stage between aging and dementia, making this population a suitable target for cognitive intervention. In MCI, not all cognitive functions are impaired and preserved functions can thus be recruited to compensate for the impact of cognitive impairment. Improving cognition may have a tremendous impact on quality of life and help delay the loss of autonomy that comes with dementia. Several studies have reported evidence of cognitive benefits following cognitive intervention in individuals with MCI. Studies that relied on training memory and attentional control have provided the most consistent evidence for cognitive gains. A few studies have investigated the neurophysiological processes by which these training effects occur. More research is needed to draw clear conclusions on the type of brain processes that are engaged in cognitive training and there are insufficient findings regarding transfer to activities of daily life. Results from recent studies using new technologies such as virtual reality provide encouraging evidence of transfer effects to real-life situations.
Philip Sayegh, David J. Moore, and Pariya Fazeli Wheeler
Since the first cluster of people with HIV was identified in 1981, significant biomedical advances, most notably the development of antiretroviral therapy (ART), have led to considerably increased life expectancy as well as a reduction in the morbidity and mortality associated with HIV/AIDS. As a result, HIV/AIDS is no longer considered a terminal illness, but rather a chronic illness, and many persons living with HIV/AIDS are beginning to enter or have already reached later life. In fact, Americans ages 50 years and older comprise approximately half of all individuals with HIV/AIDS and represent the most rapidly growing subpopulation of persons living with HIV/AIDS in the United States.
Despite significant advances in HIV/AIDS treatment and prognosis, older adults living with HIV (OALH) face a number of unique challenges and circumstances that can lead to exacerbated symptoms and poorer outcomes, despite demonstrating generally better ART adherence than their younger counterparts. These detrimental outcomes are due to both chronological aging and cohort effects as well as social and behavioral factors and long-term ART use. For instance, neurocognitive deficits and neuropsychiatric symptoms, including depression, anxiety, apathy, and fatigue, are often observed among OALH, which can result in feelings of loneliness, social isolation, and reduced social support. Taken together, these factors can lead to elevated levels of problems with everyday functioning (e.g., activities of daily living) among OALH. In addition, sociocultural factors such as race/ethnicity, ageism, sexism, homophobia, transphobia, geographic region, socioeconomic status and financial well-being, systemic barriers and disparities, and cultural values and beliefs play an influential role in determining outcomes.
Notwithstanding the challenges associated with living with HIV/AIDS in later life, many persons living with HIV/AIDS are aging successfully. HIV/AIDS survivor and community mobilization efforts, as well as integrated care models, have resulted in some significant improvements in overall HIV/AIDS patient care. In addition, interventions aimed at improving successful aging outcomes among OALH are being developed in an attempt to effectively reduce the psychological and physical morbidity associated with HIV disease.
Life is filled with goals or intentions that people hope to realize. Some of these are rather mundane (e.g., remembering to purchase a key ingredient for a recipe when stopping at the market), while others are more significant (e.g., remembering to pick up one’s child from school at the end of the day). Prospective memory represents the ability to form and then realize intentions at an appropriate time. A fundamental aspect of prospective memory is that one is engaged in one or more tasks (i.e., ongoing activities) between the formation of an intention and the opportunity to realize the goal. For instance, in the shopping example, one might form the intention at home and then travel to the market and collect several other items before walking past the desired ingredient. Considerable research has demonstrated that the efficiency of prospective memory declines with age, although age-related differences are not universal.
The neurocognitive processes underpinning age-related differences in the formation and realization of delayed intentions have been investigated in studies using event-related brain potentials. This research reveals that age-related differences in prospective memory arise from the disruption of neural systems supporting the successful encoding of intentions, the detection of prospective memory cues, and possibly processes supporting the retrieval of intentions from memory when a cue is encountered or efficiently shifting from the ongoing activity to the prospective element of the task. Therefore, strategies designed to ameliorate age-related declines in prospective memory should target a variety of processes engaged during the encoding, retrieval, and enactment of delayed intentions.
Benjamin T. Mast and Diana DiGasbarro
Clinicians conduct capacity evaluations to determine an older adult’s ability to make and execute a decision within key domains of functioning. Questions of capacity often arise when an older adult experiences a decline in cognitive functioning due to Alzheimer’s disease, stroke, or severe psychiatric illness, for example. Capacity is related to legal competency, and a lack of capacity may be proved by providing evidence that an older adult is unable to understand the act or decision in question; appreciate the context and consequences of the decision or act; reason about the potential harms and benefits; or express a choice. Capacity is domain-specific, time-specific, and decision-specific. Domains include financial capacity, medical treatment and research consent capacity, driving capacity, sexual consent capacity, and voting capacity. Each capacity domain encompasses activities that may vary in complexity or risk, and thus require different levels of capacity. For example, within the medical treatment consent capacity domain, an older adult may lack the capacity to consent to a complicated and risky surgical procedure while retaining the capacity to consent to a routine blood draw. Clinicians determine capacity by using a combination of tools including capacity assessment instruments, task-specific functional evaluations, interviews with the patient and family members, measures of cognitive functioning, and consideration of social, physical, and mental health factors. Extensive research has been conducted to determine the reliability and validity of a variety of capacity assessment instruments for many domains. These instruments generally assess the patient’s responses to vignettes pertaining to the domain in question, information gleaned from structured and semi-structured interviews, functional ability, or a combination of these methods. Although there is still need for more research, especially in emerging domains, capacity assessments help to protect vulnerable older adults from harm while allowing them to retain the highest possible level of autonomy.
Aleksandra Kudlicka and Linda Clare
The number of people living with dementia is growing, and with limited pharmacological treatment options the importance of psychosocial interventions is increasingly recognized. Cognitive rehabilitation is particularly well placed to address the needs of people living with mild and moderate dementia and their family supporters, as it offers a range of tools to tackle the complexity of the condition. It utilizes powerful approaches of problem solving and goal setting combined with evidence-based rehabilitative techniques for managing cognitive impairments. It also incorporates strategies to address emotional and motivational aspects of dementia that may affect a person’s well-being. It is provided on an individual basis, usually in people’s homes, making it directly applicable to everyday life. It is also genuinely person-centered and flexible as the therapy goals are agreed in a collaborative process between the therapist, person with dementia, and family members. Cognitive rehabilitation does not claim to address underlying pathology, but instead focuses on a person’s functional ability and enjoyment of life.
Evidence for effectiveness of cognitive rehabilitation in the context of mild and moderate dementia, mostly Alzheimer’s disease (AD), is gradually accumulating with a number of randomized control trials demonstrating that people with mild and moderate dementia can significantly improve their functioning in targeted areas. For example, the GREAT trial with 475 people with mild to moderate Alzheimer’s, vascular, and mixed dementia completed in 2017 in the United Kingdom demonstrated that cognitive rehabilitation improves everyday functioning in relation to individual therapy goals.
There is a growing interest in cognitive rehabilitation and the focus shifts to extending evidence to less-common forms of dementia, particularly in people with non-amnestic presentation. Future efforts need to concentrate on promoting the approach and optimizing application in real-life settings with the aim of maximizing benefits for people living with dementia and their families.