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.
Shellie-Anne T. Levy and Glenn E. Smith
Gianluca Susi, Jaisalmer de Frutos-Lucas, Guiomar Niso, Su Miao Ye-Chen, Luis Antón Toro, Brenda Nadia Chino Vilca, and Fernando Maestú
Oscillatory activity present in brain signals reflects the underlying time-varying electrical discharges within and between ensembles of neurons. Among the variety of non-invasive techniques available for measuring of the brain’s oscillatory activity, magnetoencephalography (MEG) presents a remarkable combination of spatial and temporal resolution, and can be used in resting-state or task-based studies, depending on the goals of the experiment. Two important kinds of analysis can be carried out with the MEG signal: spectral a. and functional connectivity (FC) a. While the former provides information on the distribution of the frequency content within distinct brain areas, FC tells us about the dependence or interaction between the signals stemming from two (or among many) different brain areas. The large frequency range combined with the good resolution offered by MEG makes MEG-based spectral and FC analyses able to highlight distinct patterns of neurophysiological alterations during the aging process in both healthy and pathological conditions. Since disruption in spectral content and functional interactions between brain areas could be accounted for by early neuropathological changes, MEG could represent a useful tool to unveil neurobiological mechanisms related to the cognitive decline observed during aging, particularly suitable for the detection of functional alterations, and then for the discovery of potential biomarkers in case of pathology. The aging process is characterized by alterations in the spectral content across the brain. At the network level, FC studies reveal that older adults experience a series of changes that make them more vulnerable to cognitive interferences. While special attention has been dedicated to the study of pathological conditions (in particular, mild cognitive impairment and Alzheimer’s disease), the lack of studies addressing the features of FC in healthy aging is noteworthy. This area of research calls for future attention because it is able to set the baseline from which to draw comparisons with different pathological conditions.
Caring for an older adult who needs help or supervision is in many cases associated with mental and physical health issues, especially if the care recipient has dementia, although positive consequences associated with caregiving have also been reported. Several theoretical models have shown the relevance of psychological variables for understanding variations in the stress process associated with caregiving and how interventions may benefit from psychological techniques and procedures. Since the 1990s it has been witnessed an increment in the number of studies aimed at analyzing caregiver health and developing and testing interventions for decreasing caregiver distress. Several examples of interventions for helping caregivers are considered empirically supported, including interventions for ethnically and culturally diverse caregivers, with psychotherapeutic and psychoeducational interventions showing strong effect sizes. However, efforts are still needed to maintain the results of the interventions in the long term and to make the interventions accessible (e.g., through technological resources) to a large number of caregivers who, because of time-pressure issues associated with caregiving or a lack of support, are not benefiting from them. Making these interventions available in routine healthcare settings would help a large population in need that presents with high levels of psychological suffering.
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.
Patrick D. Gajewski and Michael Falkenstein
Healthy aging is associated with changes in sensory, motor, cognitive, and emotional functions. Such changes depend on various factors. In particular, physical activity not only improves physical and motor but also cognitive and emotional functions. Observational (i.e., associations) and cross-sectional studies generally show a positive effect of regular physical exercise on cognition in older adults. Most longitudinal randomized controlled intervention studies also show positive effects, but the results are inconsistent due to large heterogeneity of methodological setups. Positive changes accompanying physical activity mainly impact executive functions, memory functions, and processing speed. Several factors influence the impact of physical activity on cognition, mainly the type and format of the activity. Strength training and aerobic training yield comparable but also differential benefits, and all should be used in physical activities. Also, a combination of physical activity with cognitive activity appears to enhance its effect on cognition in older age. Hence, such combined training approaches are preferable to homogeneous trainings. Studies of brain physiology changes due to physical activity show general as well as specific effects on certain brain structures and functions, particularly in the frontal cortex and the hippocampus, which are those areas most affected by advanced age. Physical activity also appears to improve cognition in patients with mild cognitive dysfunction and dementia and often ameliorates the disease symptoms. This makes physical training an important intervention for those groups of older people. Apart from cognition, physical activity leads to improvement of emotional functions. Exercise can lead to improvement of psychological well-being in older adults. Most importantly, exercise appears to reduce symptoms of depression in seniors. In future intervention studies it should be clarified who profits most from physical activity. Further, the conditions that influence the cognitive and emotional benefits older people derive from physical activity should be investigated in more detail. Finally, measures of brain activity that can be easily applied should be included as far as possible.
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.
Jessica R. Andrews-Hanna, Matthew D. Grilli, and Muireann Irish
The brain’s default network (DN) has received considerable interest in the context of so-called “normal” and pathological aging. Findings have generally been couched in support of a pessimistic view of brain aging, marked by substantial loss of structural brain integrity accompanied by a host of impairments in brain and cognitive function. A critical look at the literature, however, reveals that the standard loss of integrity, loss of function (LILF) view in normal aging may not necessarily hold with respect to the DN and the internally guided functions it supports. Many internally guided processes subserved by the DN are preserved or enhanced in cognitively healthy older adults. Moreover, differences in motivational, contextual, and physiological factors between young and older adults likely influence the extant neuroimaging and cognitive findings. Accordingly, normal aging can be viewed as a series of possibly adaptive cognitive and DN-related alterations that bolster cognitive function and promote socioemotional well-being and stability in a stage of life noted for change. On the other hand, the available evidence reveals strong support for the LILF view of the DN in neurodegenerative disorders, whereby syndromes such as Alzheimer’s disease (AD) and semantic dementia (SD), characterized by progressive atrophy to distinct DN subsystems, display distinct aberrations in autobiographical and semantic cognition. Taken together, these findings call for more naturalistic, age-appropriate, and longitudinal paradigms when investigating neurocognitive changes in aging and to adequately assess and control for differences in non-neural factors that may obscure “true” effects of normal and pathological aging. A shift in the framework with which age-related alterations in internally guided cognition are interpreted may shed important light on the neurocognitive mechanisms differentiating healthy and pathological aging, leading to a more complete picture of the aging brain in all its complexity.
Michael J. Valenzuela
Cognitive reserve refers to the many ways that neural, cognitive, and psychosocial processes can adapt and change in response to brain aging, damage, or disease, with the overarching effect of preserving cognitive function. Cognitive reserve therefore helps to explain why cognitive abilities in late life vary as dramatically as they do, and why some individuals are brittle to degenerative pathology and others exceptionally resilient. Historically, the term has evolved and at times suffered from vague, circular, and even competing notions. Fortunately, a recent broad consensus process has developed working definitions that resolve many of these issues, and here the evidence is presented in the form of a suggested Framework: Contributors to cognitive reserve, which include environmental exposures that demand new learning and intellectual challenge, genetic factors that remain largely unknown, and putative G × E interactions; mechanisms of cognitive reserve that can be studied at the biological, cognitive, or psychosocial level, with a common theme of plasticity, flexibility, and compensability; and the clinical outcome of (enriched) cognitive reserve that can be summarized as a compression of cognitive morbidity, a relative protection from incident dementia but increased rate of progression and mortality after diagnosis. Cognitive reserve therefore has great potential to address the global challenge of aging societies, yet for this potential to be realized a renewed scientific, clinical, and societal focus will be required.
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.
Margaret Kathleen Pichora-Fuller
Age-related hearing loss is heterogeneous. Multiple causes can damage the auditory system from periphery to cortex. There can be changes in thresholds for detecting sound and/or in the perception of supra-threshold sounds. Influenced by trends in neuroscience and gerontology, research has shifted from a relatively narrow modality-specific focus to a broader interest in how auditory aging interacts with other domains of aging. The importance of the connection between sensory and cognitive aging was reported based on findings from the Berlin Aging Study in the mid-1990s. Of the age-related sensory and motor declines that become more prevalent with age, hearing loss is the most common, and it is the most promising as an early marker for risk of cognitive decline and as a potentially modifiable mid-life risk factor for dementia. Hearing loss affects more than half of the population by 70 years of age and about 80% of people over 80 years of age. It is more prevalent in people with dementia than in peers with normal cognition. People with hearing loss can be up to five times more likely to develop dementia compared to those with normal hearing. Evidence from cross-sectional studies has confirmed significant correlations between hearing loss and cognitive decline in older adults. Longitudinal studies have demonstrated that hearing loss is associated with incident cognitive decline and dementia. Various biological, psychological, and social mechanisms have been hypothesized to account for these associations, but the causes remain unproven. Nevertheless, it is widely believed that there is a meaningful interface among sensory, motor, and cognitive dysfunctions in aging, with implications for issues spanning brain plasticity to quality of life. Experimental research investigating sensory-motor-cognitive interactions provides insights into how age-related declines in these domains may be exacerbated or compensated. Ongoing research on auditory aging and how it interfaces with cognitive aging is expected to increase knowledge of the neuroscience of aging, provide insights into how to optimize the everyday functioning of older adults, and inspire innovations in clinical practice and social policy.