Cognitive Changes In Aging Research Articles

Spatiotemporal Correlation between Amyloid and Tau Accumulations Underlies Cognitive Changes in Aging.

It is poorly known how Aβ and tau accumulations associate at the spatiotemporal level in the in vivo human brain to impact cognitive changes in older adults prior to AD symptoms onset. In this study, we used a graph theory-based spatiotemporal analysis to characterize the cortical patterns of Aβ and tau deposits and their relationship with cognitive changes in the Harvard Aging Brain Study (HABS) cohort. We found that the temporal accumulations of interlinked Aβ and tau pathology display distinctive spatiotemporal correlations associated with early cognitive decline. Notably, we observed that baseline Aβ deposits-Thal amyloid phase Ⅱ-related to future increase of tau deposits, Braak stages Ⅰ-Ⅳ, both displaying linkage to the decline in multi-domain cognitive scores. We also found unimodal tau-to-tau and cognitive impairment associations in broad areas of Braak stages Ⅰ-Ⅳ. The unimodal Aβ-to-Aβ progressions were not associated with cognitive changes. Our results revealed a multifaceted correlation of the spatiotemporal Aβ and tau associations with cognitive decline over time, in which tau-to-tau and tau-Aβ interactions, and not Aβ independently, might be critical contributors to clinical trajectories toward AD in older adults.

Prefrontal Cerebral Oxygenated Hemoglobin Concentration during the Category Fluency and Finger-Tapping Tasks in Adults with and without Mild Cognitive Impairment: A Near-Infrared Spectroscopy Study.

Mild cognitive impairment (MCI) is considered to be the limit between the cognitive changes of aging and early dementia; thus, discriminating between participants with and without MCI is important. In the present study, we aimed to examine the differences in the cerebral oxyhemoglobin signal between individuals with and without MCI. The cerebral oxyhemoglobin signal was measured when the participants (young and elderly controls as well as patients with MCI) performed category fluency, finger tapping, and dual tasks using head-mounted near-infrared spectroscopy; the results were compared between the groups. The cerebral oxyhemoglobin signal trended toward the highest values during the category fluency task in young participants and during the finger-tapping task in elderly participants regardless of the MCI status. The area under the curve was approximately 0.5, indicating a low discrimination ability between elderly participants with and without MCI. The measurement of the blood flow in the prefrontal cortex may not accurately quantify cognitive and motor performance to detect MCI. Finger tapping may increase cerebral blood flow in individuals with and without MCI during the task.

MCI Criteria in ADNI: Meeting Biological Expectations.

In his Clinical Note, “Amnestic MCI in ADNI: Maybe Not Enough Memory Impairment?” Duff1 raises important issues regarding the diagnosis of mild cognitive impairment (MCI). As he comments, MCI is often a transitional condition between the cognitive changes of aging and dementia. The criteria for MCI have been reasonably consistent and accepted, but the implementation of the criteria has posed significant issues.2,3

Factors contributing to cognitive improvement effects of acupuncture in patients with mild cognitive impairment: a pilot randomized controlled trial

BackgroundMild cognitive impairment (MCI) is generally regarded as the borderline between cognitive changes of aging and very early Alzheimer’s disease (AD). It is important to develop easily available interventions to delay the progression of MCI to AD. We investigated factors contributing to the cognitive improvement effects of acupuncture to obtain data for developing optimized acupuncture treatments for MCI.MethodsThis outcome assessor-blinded, randomized controlled trial included a full analysis for comparing the efficacy of different acupuncture methods. Thirty-two participants with MCI (i.e., fulfilling the Peterson diagnostic criteria for MCI, K-MMSE scores of 20–23, and MoCA-K scale scores of 0–22) were randomly assigned to basic acupuncture (BA; GV20, EX-HN1, GB20, and GV24 for 30 min), acupoint specificity (AS; adding KI3 to BA), needle duration (ND; BA for 20 min), or electroacupuncture (EA; electrical stimulation to BA) groups (n=8/group) via 1:1:1:1 allocation and administered acupuncture once daily, three times a week for 8 weeks. The measured outcomes included scores on the Korean version of the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-K-cog), Korean version of the Montreal Cognitive Assessment scale (MoCA-K), Center for Epidemiological Studies-Depression Scale, Korean Activities of Daily Living scale, Korean Instrumental Activities of Daily Living scale, and European Quality of Life Five Dimension Five Level Scale. Outcome measurements were recorded at baseline (week 0), intervention endpoint (week 8), and 12 weeks after intervention completion (week 20).ResultsTwenty-five patients with MCI completed the trial (BA group, 8; AS group, 6; ND group, 5; EA group, 6). MoCA-K scores were significantly increased in the BA group compared with the ND (p=0.008, week 8–week 0) and EA groups (p=0.003, week 8–week 0; p=0.043, week 20–week 0). ADAS-K-cog scores were significantly decreased in the BA group compared with the ND group (p=0.019, week 20–week 0).ConclusionsThe BA group showed significant improvement in cognitive function compared to the ND and EA groups. Electrical stimulation and needle duration may contribute to the cognitive improvement effects of acupuncture in patients with MCI.Trial registrationClinical Research Information Service; URL:cris.nih.go.kr.; unique identifier: KCT0003430 (registration date: January 16, 2019).

Production of Inflected Novel Words in Older Adults With and Without Dementia.

While cognitive changes in aging and neurodegenerative disease have been widely studied, language changes in these populations are less well understood. Inflecting novel words in a language with complex inflectional paradigms provides a good opportunity to observe how language processes change in normal and abnormal aging. Studies of language acquisition suggest that children inflect novel words based on their phonological similarity to real words they already know. It is unclear whether speakers continue to use the same strategy when encountering novel words throughout the lifespan or whether adult speakers apply symbolic rules. We administered a simple speech elicitation task involving Finnish-conforming pseudo-words and real Finnish words to healthy older adults, individuals with mild cognitive impairment, and individuals with Alzheimer's disease (AD) to investigate inflectional choices in these groups and how linguistic variables and disease severity predict inflection patterns. Phonological resemblance of novel words to both a regular and an irregular inflectional type, as well as bigram frequency of the novel words, significantly influenced participants' inflectional choices for novel words among the healthy elderly group and people with AD. The results support theories of inflection by phonological analogy (single-route models) and contradict theories advocating for formal symbolic rules (dual-route models).

How early can we diagnose Alzheimer disease (and is it sufficient)? The 2017 Wartenberg lecture.

A seismic shift in our understanding of the ability to diagnose Alzheimer disease (AD) is occurring. For the last several decades, AD has been a clinical–pathologic diagnosis, and this conceptualization of the disease has served the field well. Typically, the clinician would identify a syndrome such as mild cognitive impairment or dementia, and label the condition as “probable AD” since the diagnosis of definite AD could not be made until an autopsy revealed the presence of amyloid plaques and tau-based neurofibrillary tangles. However, with the advent of biomarkers for AD including neuroimaging and CSF, the identification of AD pathology can be made in life, which greatly enhances the ability of clinicians to be precise about the underlying etiology of a clinical syndrome. Hypothetical models of the temporal relation among the pathologic elements and the clinical symptoms have been proposed and have influenced the field enormously. This has enabled clinicians to be specific about the underlying cause of a given clinical syndrome. As such, the diagnostic capability of the clinician is evolving. However, AD pathology is only a component of the puzzle describing the causes of cognitive changes in aging. Most often, there is a multitude of pathologic entities contributing to the neuropathologic explanation of cognitive changes in aging. AD changes contribute important elements to the diagnosis, but the final answer is more complex. The field of aging and dementia will have to incorporate these additional elements.

Effects of Age and Working Memory Load on Syntactic Processing: An Event-Related Potential Study.

Cognitive changes in aging include working memory (WM) decline, which may hamper language comprehension. An increase in WM demands in older adults would probably provoke a poorer sentence processing performance in this age group. A way to increase the WM load is to separate two lexical units in an agreement relation (i.e., adjective and noun), in a given sentence. To test this hypothesis, event-related potentials (ERPs) were collected from Spanish speakers (30 older adults, mean age = 66.06 years old; and 30 young adults, mean age = 25.7 years old) who read sentences to detect grammatical errors. The sentences varied with regard to (1) the gender agreement of the noun and adjective, where the gender of the adjective either agreed or disagreed with the noun, and (2) the WM load (i.e., the number of words between the noun and adjective in the sentence). No significant behavioral differences between groups were observed in the accuracy of the response, but older adults showed longer reaction times regardless of WM load condition. Compared with young participants, older adults showed a different pattern of ERP components characterized by smaller amplitudes of LAN, P600a, and P600b effects when the WM load was increased. A smaller LAN effect probably reflects greater difficulties in processing the morpho-syntactic features of the sentence, while smaller P600a and P600b effects could be related to difficulties in recovering and mapping all sentence constituents. We concluded that the ERP pattern in older adults showed subtle problems in syntactic processing when the WM load was increased, which was not sufficient to affect response accuracy but was only observed to result in a longer reaction time.

Strategies for Preventing Cognitive Decline in Healthy Older Adults

Many advances have been made in the understanding of age-related changes in cognition. As research details the cognitive and neurobiological changes that occur in aging, there is increased interest in developing and understanding methods to prevent, slow, or reverse the cognitive decline that may occur in normal healthy older adults. The Institute of Medicine has recently recognized cognitive aging as having important financial and public health implications for society with the increasing older adult population worldwide. Cognitive aging is not dementia and does not result in the loss of neurons but rather changes in neurotransmission that affect brain functioning. The fact that neurons are structurally intact but may be functionally affected by increased age implies that there is potential for remediation. This review article presents recent work using medication-based strategies for slowing cognitive changes in aging. The primary method presented is a hormonal approach for affecting cognition in older women. In addition, a summary of the work examining modifiable lifestyle factors that have shown promise in benefiting cognition in both older men and women is described. Much work remains to be done so that evidence-based recommendations can be made for slowing cognitive decline in healthy older adults. The success of some of these methods thus far indicates that the brains of healthy older adults are plastic enough to be able to respond to these cognitive decline prevention strategies, and further work is needed to define the most beneficial methods.

Sensitive performance-based assessment of everyday action in older and younger adults

ABSTRACTEveryday function is compromised by mild cognitive changes in aging. These changes predict risk for future decline and dementia but remain poorly characterized, largely due to a scarcity of sensitive, objective measures.Twenty-seven younger adults and 25 non-demented older adults completed the Naturalistic Action Test (NAT), a performance-based measure of everyday action involving simple and complex tasks. Performance was coded for overt errors and subtle inefficiencies. Participants also completed self-report functional measures and cognitive tests. Mixed ANOVAs revealed that older adults made more subtle NAT errors with high task demands; groups did not differ in overt errors. Correlations did not reveal significant relations between self-report and NAT errors, but NAT performance was correlated with learning and recall.The NAT provides a promising tool for detecting subtle age-related changes and examining decline across levels of impairment. Self-report may lack sensitivity to subtle changes, and episodic memory changes underlie early functional disruption.

Stress and Relaxation Among Aging Catholic Priests

ABSTRACTUsing semistructured interviews, this study considered how currently active priests (n = 18) perceived physical and cognitive changes of aging, stress in their lives, and self-care. Half summarized their ministry by choosing the statement, “I’m satisfied with my life, but sometimes the days are too long.” Most respondents found there were energy limitations with aging and reported health concerns that did not significantly limit pastoral activities. All were conscious of healthy self-care (diet, exercise, and medical care). Stress for most respondents came from pastoral demands of parishioners and hierarchs, their own demands for meeting the needs of all, and loneliness.

A novel biomarker of amnestic MCI based on dynamic cross-frequency coupling patterns during cognitive brain responses.

The detection of mild cognitive impairment (MCI), the transitional stage between normal cognitive changes of aging and the cognitive decline caused by AD, is of paramount clinical importance, since MCI patients are at increased risk of progressing into AD. Electroencephalographic (EEG) alterations in the spectral content of brainwaves and connectivity at resting state have been associated with early-stage AD. Recently, cognitive event-related potentials (ERPs) have entered into the picture as an easy to perform screening test. Motivated by the recent findings about the role of cross-frequency coupling (CFC) in cognition, we introduce a relevant methodological approach for detecting MCI based on cognitive responses from a standard auditory oddball paradigm. By using the single trial signals recorded at Pz sensor and comparing the responses to target and non-target stimuli, we first demonstrate that increased CFC is associated with the cognitive task. Then, considering the dynamic character of CFC, we identify instances during which the coupling between particular pairs of brainwave frequencies carries sufficient information for discriminating between normal subjects and patients with MCI. In this way, we form a multiparametric signature of impaired cognition. The new composite biomarker was tested using data from a cohort that consists of 25 amnestic MCI patients and 15 age-matched controls. Standard machine-learning algorithms were employed so as to implement the binary classification task. Based on leave-one-out cross-validation, the measured classification rate was found reaching very high levels (95%). Our approach compares favorably with the traditional alternative of using the morphology of averaged ERP response to make the diagnosis and the usage of features from spectro-temporal analysis of single-trial responses. This further indicates that task-related CFC measurements can provide invaluable analytics in AD diagnosis and prognosis.

Brain Events Underlying Episodic Memory Changes in Aging: A Longitudinal Investigation of Structural and Functional Connectivity.

Episodic memories are established and maintained by close interplay between hippocampus and other cortical regions, but degradation of a fronto-striatal network has been suggested to be a driving force of memory decline in aging. We wanted to directly address how changes in hippocampal-cortical versus striatal-cortical networks over time impact episodic memory with age. We followed 119 healthy participants (20-83 years) for 3.5 years with repeated tests of episodic verbal memory and magnetic resonance imaging for quantification of functional and structural connectivity and regional brain atrophy. While hippocampal-cortical functional connectivity predicted memory change in young, changes in cortico-striatal functional connectivity were related to change in recall in older adults. Within each age group, effects of functional and structural connectivity were anatomically closely aligned. Interestingly, the relationship between functional connectivity and memory was strongest in the age ranges where the rate of reduction of the relevant brain structure was lowest, implying selective impacts of the different brain events on memory. Together, these findings suggest a partly sequential and partly simultaneous model of brain events underlying cognitive changes in aging, where different functional and structural events are more or less important in various time windows, dismissing a simple uni-factorial view on neurocognitive aging.

Stochastic cortical neurodynamics underlying the memory and cognitive changes in aging

The relatively random spiking times of individual neurons provide a source of noise in the brain. We show how this noise interacting with altered depth in the basins of attraction of networks involved in short-term memory, attention, and episodic memory provide an approach to understanding some of the cognitive changes in normal aging. The effects of the neurobiological changes in aging that are considered include reduced synaptic modification and maintenance during learning produced in part through reduced acetylcholine in normal aging, reduced dopamine which reduces NMDA-receptor mediated effects, reduced noradrenaline which increases cAMP and thus shunts excitatory synaptic inputs, and the effects of a reduction in acetylcholine in increasing spike frequency adaptation. Using integrate-and-fire simulations of an attractor network implementing memory recall and short-term memory, it is shown that all these changes associated with aging reduce the firing rates of the excitatory neurons, which in turn reduce the depth of the basins of attraction, resulting in a much decreased probability in maintaining in short-term memory what has been recalled from the attractor network. This stochastic dynamics approach opens up new ways to understand and potentially treat the effects of normal aging on memory and cognitive functions.

Age-related effects on spatial memory across viewpoint changes relative to different reference frames.

Remembering object positions across different views is a fundamental competence for acting and moving appropriately in a large-scale space. Behavioural and neurological changes in elderly subjects suggest that the spatial representations of the environment might decline compared to young participants. However, no data are available on the use of different reference frames within topographical space in aging. Here we investigated the use of allocentric and egocentric frames in aging, by asking young and older participants to encode the location of a target in a virtual room relative either to stable features of the room (allocentric environment-based frame), or to an unstable objects set (allocentric objects-based frame), or to the viewer's viewpoint (egocentric frame). After a viewpoint change of 0° (absent), 45° (small) or 135° (large), participants judged whether the target was in the same spatial position as before relative to one of the three frames. Results revealed a different susceptibility to viewpoint changes in older than young participants. Importantly, we detected a worst performance, in terms of reaction times, for older than young participants in the allocentric frames. The deficit was more marked for the environment-based frame, for which a lower sensitivity was revealed as well as a worst performance even when no viewpoint change occurred. Our data provide new evidence of a greater vulnerability of the allocentric, in particular environment-based, spatial coding with aging, in line with the retrogenesis theory according to which cognitive changes in aging reverse the sequence of acquisition in mental development.

A SUITE OF DISCRIMINATION TASKS TO BEHAVIORALLY ASSESS THE INTEGRITY OF HIPPOCAMPAL PATTERN SEPARATION AND INDIVIDUAL DIFFERENCES IN NEUROCOGNITIVE AGING

The hippocampus is a critical brain region for episodic memory. It is hypothesized that one of its core computations is pattern separation, the process of disambiguating similar neural inputs into distinct orthogonal representations, a process that depends on the dentate (DG) and CA3 regions. We have previously shown that DG/CA3 pattern separation is reduced in aging (manifesting as a functional rigidity in this region), which is also linked to perforant path integrity as well as performance on neuropsychological tasks that involve fine-level discriminations among mnemonic representations. The latter approach continues to be neurobiologically validated, but it also expanded here to include tasks that assess discrimination along several dimensions of memory (object, spatial, temporal). In the object discrimination task, subjects incidentally encode pictures and during test they view some of the same items (targets), some new items (foils), and some similar items (lures). They are asked to make a recognition judgment. In the spatial discrimination task, participants incidentally encode objects presented in 1 of 31 possible locations and during test they view the same objects and asked to indicate whether the location of the items has changed from study. Some items are presented in exactly the same location and some are presented in different locations on the screen. In the temporal discrimination task, participants incidentally encode objects in sequences of 30 items and during are shown pairs of objects that were presented during study and asked to indicate which one was presented first. We show that older adults can exhibit one of two neuropsychological profiles across all tasks: (1) mild deficits with a recovery (relative to young) at the lowest levels of interference (aged-unimpaired AU), or (2) more severe deficits with no recovery even when interference is minimized (aged-impaired AI). We suggest that the AI group is likely more susceptible to AD brain pathologies and propose that our tools can be used as an early diagnostic/risk marker. These translational tools bridge from computational and animal models of episodic memory to human cognition and significantly expand our understanding of cognitive changes in aging and Alzheimer's disease.

Protecting the Brain: What's the Evidence Behind Strategies to Mitigate Cognitive Aging?

Protecting the Brain: What's the Evidence Behind Strategies to Mitigate Cognitive Aging?

Chronological age and age-related cognitive deficits are associated with an increase in multiple types of driving errors in late life.

Older driver research has mostly focused on identifying that small proportion of older drivers who are unsafe. Little is known about how normal cognitive changes in aging affect driving in the wider population of adults who drive regularly. We evaluated the association of cognitive function and age with driving errors. A sample of 266 drivers aged 70 to 88 years were assessed on abilities that decline in normal aging (visual attention, processing speed, inhibition, reaction time, task switching) and the UFOV®, which is a validated screening instrument for older drivers. Participants completed an on-road driving test. Generalized linear models were used to estimate the associations of cognitive factors with specific driving errors and number of errors in self-directed and instructor navigated conditions. All error types increased with chronological age. Reaction time was not associated with driving errors in multivariate analyses. A cognitive factor measuring speeded selective attention and switching was uniquely associated with the most errors types. The UFOV® predicted blind-spot errors and errors on dual carriageways. After adjusting for age, education, and gender, the cognitive factors explained 7% of variance in the total number of errors in the instructor-navigated condition and 4% of variance in the self-navigated condition. We conclude that among older drivers, errors increase with age and are associated with speeded selective attention, particularly when that requires attending to the stimuli in the periphery of the visual field, task switching, errors inhibiting responses, and visual discrimination. These abilities should be the target of cognitive training.

Early diagnosis of Alzheimer's disease: is MCI too late?

The field of aging and dementia research is advancing rapidly toward the stage of earlier identification of clinical symptoms. Ultimately, clinicians would like to be able to identify individuals who are asymptomatic but at risk for developing dementia. In the interim, the construct of mild cognitive impairment (MCI) has come to represent an intermediate clinical state between the cognitive changes of aging and the very earliest features of Alzheimer's disease. A great deal of research has been generated in the past several years on MCI, and epidemiologic studies are characterizing its frequency in the general population. There are predictors of a more rapid progression from MCI to Alzheimer's disease, and these studies are suggesting techniques for altering future clinical trials. The neuropathology of MCI is intermediate between the neuropathologic changes of aging and fully developed Alzheimer's disease. The breadth of research in MCI is expanding and will be reviewed.

Developing assistive web‐base technologies for adults with age‐related cognitive impairments

PurposeLittle systematic applied research has been conducted on how age‐related cognitive impairments might affect older adults' usage of web service and this paper aims to fill some of that gap.Design/methodology/approachAn analysis of the relationship between the cognitive changes of aging and the usage of web services. Supported by field research with the key stakeholders, including older adults and organisations that provide services for older adults. This consists of focus group sessions with key stakeholders and individual interviews with older adult users. Older adult users also complete an online form using a think aloud protocol. The data are analysed using a thematic content analysis technique.FindingsIssues around older adults' relationship with technology and the challenges they face along with the strengths and weaknesses of online forms and means to improve them. In particular, there are issues of fear and frustration, inconsistency and visual clutter, and a feeling of neglect by service providers. Users also identify a strong need for human rather than machine support when struggling with the technology.Research limitations/implicationsThe findings only now being applied to an existing system in the Delivering Inclusive Access to Disabled and Elderly Members (DIADEM) project and it still needs to evaluate of usability of DIADEM. Further research also needs to consider the technology adoption model for system like DIADEM.Practical implicationsThe findings have implications in form design and transaction delivery for online services.Originality/valueThe perception of neglect by service providers is new and this with the needs for consistency and for human support lead to novel approaches in the DIADEM system.

Dehydroepiandrosterone replacement therapy—panacea, snake oil, or a bit of both?

Age-related declines in dehydroepiandrosterone sulfate concentration parallel the physical and cognitive changes of aging. This observation suggests that these events are causally related and that replacement therapy might have beneficial effects in the elderly. The authors of this Viewpoint consider the evidence for, and against, such an approach.