Behavioral prevention strategies can help maintain high levels of cognition and functional integrity, and can reduce the social, medical, and economic burden associated with cognitive aging and ...age-associated neurodegenerative diseases. Interventions involving physical exercise and cognitive training have consistently shown positive effects on cognition in older adults. "Brain fitness" interventions have now been shown to have sustained effects lasting 10 years or more. A meta-analysis suggests these physical exercise and brain fitness exercises produce nearly identical impact on formal measures of cognitive function. Behavioral interventions developed and deployed by psychologists are key in supporting healthy cognitive aging. The National Institutes of Health should expand research on cognitive health and behavioral and social science to promote healthy aging and to develop and refine ways to prevent and treat dementia. Funding for adequately powered, large-scale trials is needed. Congress must maintain support for crucial dementia-related initiatives like the Centers for Disease Control and Prevention Healthy Brain Initiative and fund training programs to insure there is a work force with skills to provide high quality care for older adults. Insurers must provide better coverage for behavioral interventions. Better coverage is needed so there can be increased access to evidence-based disease prevention and health promotion services with the potential for reducing dementia risk.
This virtual issue consists of studies previously published in the Journal of the International Neuropsychological Society and selected on the basis of their content related to one of the most highly ...researched concepts in behavioral neurology and neuropsychology over the past decade: mild cognitive impairment (MCI). The reliance on cognitive screening measures, staging-based rating scales, and limited neuropsychological testing in diagnosing MCI across most research studies may miss individuals with subtle cognitive declines or mis-diagnose MCI in those who are otherwise cognitively normal on a broader neuropsychological battery of tests. The assembled articles highlight the perils of relying on these conventional criteria for MCI diagnosis and reveal how the reliability of diagnosis is improved when sound neuropsychological approaches are adopted. When these requirements are met, we illustrate with a second series of articles that neuropsychological measures associate strongly with biomarkers and often reflect pathology beyond or instead of typical AD distributions. The final set of articles reveal that people with MCI demonstrate mild but identifiable functional difficulties, and a challenge for neuropsychology is how to incorporate this information to better define MCI and distinguish it from early dementia. Neuropsychology is uniquely positioned to improve upon the state of the science in MCI research and practice by providing critically important empirical information on the specific cognitive domains affected by the predominant neurodegenerative disorders of late life as well as on the diagnostic decision-making strategies used in studies. When such efforts to more comprehensively assess neuropsychological functions are undertaken, better characterizations of spared and impaired cognitive and functional abilities result and lead to more convincing associations with other biomarkers as well as to prediction of clinical outcomes.
OBJECTIVES: To investigate the efficacy of a novel brain plasticity–based computerized cognitive training program in older adults and to evaluate the effect on untrained measures of memory and ...attention and participant‐reported outcomes.
DESIGN: Multisite randomized controlled double‐blind trial with two treatment groups.
SETTING: Communities in northern and southern California and Minnesota.
PARTICIPANTS: Community‐dwelling adults aged 65 and older (N=487) without a diagnosis of clinically significant cognitive impairment.
INTERVENTION: Participants were randomized to receive a broadly‐available brain plasticity–based computerized cognitive training program (intervention) or a novelty‐ and intensity‐matched general cognitive stimulation program modeling treatment as usual (active control). Duration of training was 1 hour per day, 5 days per week, for 8 weeks, for a total of 40 hours.
MEASUREMENTS: The primary outcome was a composite score calculated from six subtests of the Repeatable Battery for the Assessment of Neuropsychological Status that use the auditory modality (RBANS Auditory Memory/Attention). Secondary measures were derived from performance on the experimental program, standardized neuropsychological assessments of memory and attention, and participant‐reported outcomes.
RESULTS: RBANS Auditory Memory/Attention improvement was significantly greater (P=.02) in the experimental group (3.9 points, 95% confidence interval (CI)=2.7–5.1) than in the control group (1.8 points, 95% CI=0.6–3.0). Multiple secondary measures of memory and attention showed significantly greater improvements in the experimental group (word list total score, word list delayed recall, digits backwards, letter–number sequencing; P<.05), as did the participant‐reported outcome measure (P=.001). No advantage for the experimental group was seen in narrative memory.
CONCLUSION: The experimental program improved generalized measures of memory and attention more than an active control program.
The aim of this study was to determine whether the TAR DNA-binding protein of 43 kDa (TDP-43) has any independent effect on the clinical and neuroimaging features typically ascribed to Alzheimer’s ...disease (AD) pathology, and whether TDP-43 pathology could help shed light on the phenomenon of resilient cognition in AD. Three-hundred and forty-two subjects pathologically diagnosed with AD were screened for the presence, burden and distribution of TDP-43. All had been classified as cognitively impaired or normal, prior to death. Atlas-based parcellation and voxel-based morphometry were used to assess regional atrophy on MRI. Regression models controlling for age at death, apolipoprotein
ε
4 and other AD-related pathologies were utilized to explore associations between TDP-43 and cognition or brain atrophy, stratified by Braak stage. In addition, we determined whether the effects of TDP-43 were mediated by hippocampal sclerosis. One-hundred and ninety-five (57 %) cases were TDP-positive. After accounting for age, apolipoprotein
ε
4 and other pathologies, TDP-43 had a strong effect on cognition, memory loss and medial temporal atrophy in AD. These effects were not mediated by hippocampal sclerosis. TDP-positive subjects were 10× more likely to be cognitively impaired at death compared to TDP-negative subjects. Greater cognitive impairment and medial temporal atrophy were associated with greater TDP-43 burden and more extensive TDP-43 distribution. TDP-43 is an important factor in the manifestation of the clinico-imaging features of AD. TDP-43 also appears to be able to overpower what has been termed resilient brain aging. TDP-43 therefore should be considered a potential therapeutic target for the treatment of AD.
Objective:
Rapid eye movement sleep behavior disorder (RBD) is associated with neurodegenerative disease and particularly with the synucleinopathies. Convenience samples involving subjects with ...idiopathic RBD have suggested an increased risk of incident mild cognitive impairment (MCI), dementia (usually dementia with Lewy bodies), and Parkinson disease (PD). There are no data on such risks in a population‐based sample.
Methods:
Cognitively normal subjects aged 70 to 89 years in a population‐based study of aging who screened positive for probable RBD using the Mayo Sleep Questionnaire were followed at 15‐month intervals. In a Cox proportional hazards model, we measured the risk of developing MCI, dementia, and PD among the exposed (probable RBD pRBD+) and unexposed (pRBD−) cohorts.
Results:
Forty‐four subjects with pRBD+ status at enrollment (median duration of pRBD features was 7.5 years) and 607 pRBD− subjects were followed prospectively for a median of 3.8 years. Fourteen of the pRBD+ subjects developed MCI, and 1 developed PD (15/44 = 34% developed MCI/PD); none developed dementia. After adjustment for age, sex, education, and medical comorbidity, pRBD+ subjects were at increased risk of MCI/PD (hazard ratio HR, 2.2; 95% confidence interval CI, 1.3–3.9; p = 0.005). Inclusion of subjects who withdrew from the study produced similar results, as did exclusion of subjects with medication‐associated RBD. Duration of pRBD symptoms did not predict the development of MCI/PD (HR, 1.05 per 10 years; 95% CI, 0.84–1.3; p = 0.68).
Interpretation:
In this population‐based cohort study, we observed that pRBD confers a 2.2‐fold increased risk of developing MCI/PD over 4 years. ANN NEUROL 2012;71:49–56
Neuropsychology of aging Cohen, Ronald A; Marsiske, Michael M; Smith, Glenn E
Handbook of clinical neurology,
2019, Volume:
167
Journal Article
Peer reviewed
All people want to age "successfully," maintaining functional capacity and quality of life as they reach advanced age. Achieving this goal depends on preserving optimal cognitive and brain ...functioning. Yet, significant individual differences exist in this regard. Some older adults continue to retain most cognitive abilities throughout their lifetime. Others experience declines in cognitive and functional capacity that range from mild decrements in certain cognitive functions over time to severe dementia among those with neurodegenerative diseases. Even among relatively healthy "successful agers," certain cognitive functions are reduced from earlier levels. This is particularly true for cognitive functions that are dependent on cognitive processing speed and efficiency. Working memory and executive and attentional functions tend to be most vulnerable. Learning and memory functions are also usually reduced, although in the absence of neurodegenerative disease learning and retrieval efficiency rather than memory storage are affected. Other functions, such as visual perception, language, semantics, and knowledge, are often well preserved. Structural, functional, and physiologic/metabolic brain changes correspond with age-associated cognitive decline. Physiologic and metabolic mechanisms, such as oxidative stress and neuroinflammation, may contribute to these changes, along with the contribution of comorbidities that secondarily affect the brain of older adults. Cognitive frailty often corresponds with physical frailty, both affected by multiple exogenous and endogenous factors. Neuropsychologic assessment provides a way of measuring the cognitive and functional status of older adults, which is useful for monitoring changes that may be occurring. Neuroimaging is also useful for characterizing age-associated structural, functional, physiologic, and metabolic brain changes, including alterations in cerebral blood flow and metabolite concentrations. Some interventions that may enhance cognitive function, such as cognitive training, neuromodulation, and pharmacologic approaches, exist or are being developed. Yet, preventing, slowing, and reversing the adverse effects of cognitive aging remains a challenge.
Research has increasingly suggested a benefit to combining multiple cognitive or behavioral strategies in a single treatment program for cognitively impaired older adults. Therefore, this systematic ...review and meta-analysis aimed to summarize results on the effects of multimodal cognitive and behavioral interventions versus control conditions on changes in cognition and mood in patients with mild cognitive impairment (pwMCI).
The review followed a general PRISMA guideline for systematic literature review with a format consisting of participants, interventions, comparators, and outcomes (PICO). Multilevel meta-analyses of aggregated efficacy were performed to assess the pooled effect sizes for cognitive and mood outcomes. Risk-of-bias, heterogeneity across studies, and publication bias were assessed for each outcome.
After primary and reference searches, 18 studies with low or some concerns of risk of bias were included. Low heterogeneity was found for mood and cognition. Funnel plots did not indicate publication bias. All the studies assessed changes in cognition (
= 1,555) while seven studies with mood outcomes (
= 343) were included. Multilevel meta-analyses demonstrated moderate effect (Hedge's
= 0.44, 95% CI = 0.21-0.67) in cognitive outcomes and large effect in mood (
= 0.65, 95% CI = 0.37-0.93). Subdomain analyses found low-moderate effects in global cognition, verbal and non-verbal memory, executive function, visuospatial abilities, and semantic fluency (0.20 <
< 0.50).
These findings showed comparable to larger effects of multimodal cognitive and behavioral interventions on cognition than pharmacological treatment. Future studies should focus on the longitudinal effects of multimodal interventions in delaying dementia.
: PROSEPRO, CRD42022349297.
Abstract Objective To validate a questionnaire focused on rapid eye movement sleep (REM) sleep behavior disorder (RBD) among participants in an aging and dementia cohort. Background RBD is a ...parasomnia that can develop in otherwise neurologically-normal adults as well as in those with a neurodegenerative disease. Confirmation of RBD requires polysomnography (PSG). A simple screening measure for RBD is desirable for clinical and research purposes. Methods We had previously developed the Mayo Sleep Questionnaire (MSQ), a 16 item measure, to screen for the presence of RBD and other sleep disorders. We assessed the validity of the MSQ by comparing the responses of patients’ bed partners with the findings on PSG. All subjects recruited in the Mayo Alzheimer’s Disease Research Center at Mayo Clinic Rochester and Mayo Clinic Jacksonville from 1/00 to 7/08 who had also undergone a PSG were the focus of this analysis. Results The study sample was comprised of 176 subjects (150 male; median age 71 years (range 39–90)), with the following clinical diagnoses: normal ( n = 8), mild cognitive impairment ( n = 44), Alzheimer’s disease ( n = 23), dementia with Lewy bodies ( n = 74), as well as other dementia and/or parkinsonian syndromes ( n = 27). The core question on recurrent dream enactment behavior yielded a sensitivity (SN) of 98% and specificity (SP) of 74% for the diagnosis of RBD. The profile of responses on four additional subquestions on RBD and one on obstructive sleep apnea improved specificity. Conclusions These data suggest that among aged subjects with cognitive impairment and/or parkinsonism, the MSQ has adequate SN and SP for the diagnosis of RBD. The utility of this scale in other patient populations will require further study.
To determine the rate of progression of mild cognitive impairment (MCI) to dementia with Lewy bodies (DLB).
We followed 337 patients with MCI in the Mayo Alzheimer's Disease Research Center (range ...2-12 years). Competing risks survival models were used to examine the rates of progression to clinically probable DLB and Alzheimer disease (AD). A subset of patients underwent neuropathologic examination.
In this clinical cohort, 116 remained as MCI, while 49 progressed to probable DLB, 162 progressed to clinically probable AD, and 10 progressed to other dementias. Among nonamnestic MCI, progression rate to probable DLB was 20 events per 100 person-years and to probable AD was 1.6 per 100 person-years. Among amnestic MCI, progression rate to probable AD was 17 events per 100 person-years, and to DLB was 1.5 events per 100 person-years. In 88% of those who developed probable DLB, the baseline MCI diagnosis included attention and/or visuospatial deficits. Those who developed probable DLB were more likely to have baseline daytime sleepiness and subtle parkinsonism. In 99% of the clinically probable AD group, the baseline MCI diagnosis included memory impairment. Neuropathologic confirmation was obtained in 24 of 30 of those with clinically probable AD, and in 14 of 18 of those with clinically probable DLB.
In a clinical sample, patients with nonamnestic MCI were more likely to develop DLB, and those with amnestic MCI were more likely to develop probable AD.
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