History of traumatic brain injury is associated with increased grey-matter loss in patients with mild cognitive impairment.

OBJECTIVES: To investigate whether a history of traumatic brain injury (TBI) is associated with greater long-term grey-matter loss in patients with mild cognitive impairment (MCI). METHODS: 85 patients with MCI were identified, including 26 with a previous history of traumatic brain injury (MCI[TBI-]) and 59 without (MCI[TBI+]). Cortical thickness was evaluated by segmenting T1-weighted MRI scans acquired longitudinally over a 2-year period. Bayesian multilevel modelling was used to evaluate group differences in baseline cortical thickness and longitudinal change, as well as group differences in neuropsychological measures of executive function. RESULTS: At baseline, the MCI[TBI+] group had less grey matter within right entorhinal, left medial orbitofrontal and inferior temporal cortex areas bilaterally. Longitudinally, the MCI[TBI+] group also exhibited greater longitudinal declines in left rostral middle frontal, the left caudal middle frontal and left lateral orbitofrontal areas sover the span of 2 years (median = 1-2%, 90%HDI [-0.01%: -0.001%], probability of direction (PD) = 90-99%). The MCI[TBI+] group also displayed greater longitudinal declines in Trail-Making-Test (TMT)-derived ratio (median: 0.737%, 90%HDI: [0.229%: 1.31%], PD = 98.8%) and differences scores (median: 20.6%, 90%HDI: [-5.17%: 43.2%], PD = 91.7%). CONCLUSIONS: Our findings support the notion that patients with MCI and a history of TBI are at risk of accelerated neurodegeneration, displaying greatest evidence for cortical atrophy within the left middle frontal and lateral orbitofrontal frontal cortex. Importantly, these results suggest that long-term TBI-mediated atrophy is more pronounced in areas vulnerable to TBI-related mechanical injury, highlighting their potential relevance for diagnostic forms of intervention in TBI.

Evaluating functional abilities within the context of memory assessment: A practice survey of neuropsychologists.

Objective: Functioning in daily life is an important consideration when differentiating between individuals with normal cognition, mild neurocognitive disorder, and major neurocognitive disorder. Despite this, there is no gold standard measurement approach for assessing functional abilities and few guidelines on how to do so. The objective of this study was to examine neuropsychologists' practices regarding the assessment of functional abilities across the spectrum of memory ability. Method: A total of 278 psychologists who routinely conduct neuropsychological assessments completed an online survey (estimated 15% response rate) querying their practices and perspectives with respect to the assessment of functional abilities. Results: Respondents identified that changes to several components of daily functioning, including activities of daily living, were important when evaluating functional abilities. Respondents reported utilizing a variety of instruments to assess functioning, with an overwhelming majority indicating the use of semi-structured interviews. Although most respondents are satisfied with existing tools, a quarter of respondents felt strongly that there was a need for more instruments of everyday functioning. Respondents further indicated that their recommendations to patients, particularly regarding compensatory strategies and follow-up with other professionals, were informed by results of their functional assessment. Conclusions: Overall, our survey results indicate that neuropsychologists perceive multiple factors of daily life to be important considerations when evaluating functioning, use a variety of techniques to assess functioning, and perceive a need for more measures of functional abilities.

Feasibility, Acceptability, and Impact of a self-guided e-learning Memory and Brain Health Promotion Program for Healthy Older Adults.

OBJECTIVES: To examine the feasibility (e.g., completion rate), acceptability (e.g., satisfaction), and participant-reported impact (e.g., memory concerns, behavior change, goal attainment) of a self-guided, e-learning adaptation of a validated, facilitator-guided, in-person memory intervention for older adults. METHODS: Participants were 139 healthy older adults (mean age: 73 ± 7, 73% women). Participation tracking and pre/post questionnaires embedded within the e-learning program were used to assess feasibility, acceptability, and impact. RESULTS: Sixty-eight percent of participants completed the program. Anonymous feedback data indicated a high level of satisfaction with the program, the pace and clarity of the learning modules, and the user interface. Suggested improvements included offering more interaction with others and addressing minor platform glitches. There was a 41% decrease in the prevalence of concern about memory changes from baseline to posttest. The majority of participants reported an increase in use of memory strategies and uptake of health-promoting lifestyle behaviors. All participants reported moderate-to-high satisfaction with personal goal attainment. CONCLUSIONS: The program demonstrated good feasibility, acceptability, and lead to reduction in age-related memory concerns. CLINICAL IMPLICATIONS: Self-guided, e-learning programming shows promise for fostering positive adaptation to age-related memory changes and improving the uptake of evidence-based strategies to promote brain health among older adults.

Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative.

INTRODUCTION: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aß)42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD). RESULTS: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aß42/40 . DISCUSSION: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.

Neuropsychiatric Symptom Burden across Neurodegenerative Disorders and its Association with Function.

OBJECTIVE: Neuropsychiatric symptoms (NPS) are prevalent in neurodegenerative disorders, however, their frequency and impact on function across different disorders is not well understood. We compared the frequency and severity of NPS across Alzheimer's disease (AD) (either with mild cognitive impairment or dementia), Cerebrovascular disease (CVD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and explored the association between NPS burden and function. METHODS: We obtained data from Ontario Neurodegenerative Disease Research Initiative (ONDRI) that included following cohorts: AD (N = 111), CVD (N = 148), PD (N = 136), FTD (N = 50) and ALS (N = 36). We compared the frequency and severity of individual NPS (assessed by the neuropsychiatric inventory questionnaire) across cohorts using generalized estimating equations and analysis of variance. Second, we assessed the relationship of NPS burden with instrumental (iADLs) and basic (ADLs) activities of living across cohorts using multivariate linear regression while adjusting for relevant demographic and clinical covariates. RESULTS: Frequency of NPS varied across cohorts (χ2(4) = 34.4, p < .001), with post-hoc tests showing that FTD had the greatest frequency as compared to all other cohorts. The FTD cohort also had the greatest severity of NPS (H(4) = 34.5, p < .001). Further, there were differences among cohorts in terms of the association between NPS burden and ADLs (F(4,461) = 3.1, p = 0.02). Post-hoc comparisons suggested that this finding was driven by the FTD group, however, the differences did not remain significant following Bonferroni correction. There were no differences among cohorts in terms of the association between NPS burden and IADLs. CONCLUSIONS: NPS frequency and severity are markedly greater in FTD as compared to other neurodegenerative diseases. Further, NPS burden appears to be associated differently with function across neurodegenerative disorders, highlighting the need for individualized clinical interventions.

White matter hyperintensity burden predicts cognitive but not motor decline in Parkinson's disease: results from the Ontario Neurodegenerative Diseases Research Initiative.

BACKGROUND AND PURPOSE: The pathophysiology of Parkinson's disease (PD) negatively affects brain network connectivity, and in the presence of brain white matter hyperintensities (WMHs) cognitive and motor impairments seem to be aggravated. However, the role of WMHs in predicting accelerating symptom worsening remains controversial. The objective was to investigate whether location and segmental brain WMH burden at baseline predict cognitive and motor declines in PD after 2 years. METHODS: Ninety-eight older adults followed longitudinally from Ontario Neurodegenerative Diseases Research Initiative with PD of 3-8 years in duration were included. Percentages of WMH volumes at baseline were calculated by location (deep and periventricular) and by brain region (frontal, temporal, parietal, occipital lobes and basal ganglia + thalamus). Cognitive and motor changes were assessed from baseline to 2-year follow-up. Specifically, global cognition, attention, executive function, memory, visuospatial abilities and language were assessed as were motor symptoms evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III, spatial-temporal gait variables, Freezing of Gait Questionnaire and Activities Specific Balance Confidence Scale. RESULTS: Regression analysis adjusted for potential confounders showed that total and periventricular WMHs at baseline predicted decline in global cognition (p < 0.05). Also, total WMH burden predicted the decline of executive function (p < 0.05). Occipital WMH volumes also predicted decline in global cognition, visuomotor attention and visuospatial memory declines (p < 0.05). WMH volumes at baseline did not predict motor decline. CONCLUSION: White matter hyperintensity burden at baseline predicted cognitive but not motor decline in early to mid-stage PD. The motor decline observed after 2 years in these older adults with PD is probably related to the primary neurodegenerative process than comorbid white matter pathology.

Implicit processes enhance cognitive abilities in mild cognitive impairment.

Previous work has shown that older adults with typical age-related memory changes (i.e., without cognitive impairment) pick up irrelevant information implicitly, and unknowingly use that information when it becomes relevant to a later task. Here, we address the possibility that implicit processes play a similarly beneficial role in the cognitive abilities of individuals with amnestic mild cognitive impairment (aMCI). Twenty-two individuals with aMCI and 22 matched controls participated in a picture judgment task while instructed to ignore distractions in the form of word/non-word letter strings. Memory for the distracting words was later tested with a word-fragment completion task. Both groups showed a priming effect, that is, they were significantly more likely to solve fragments of previously presented than non-presented words. However, the aMCI group had significantly higher scores than the older adults without cognitive impairment, t(42) = 2.16, p < .05, Cohen's d = 0.67. Our findings suggest that individuals with aMCI can enhance their performance on an explicit cognitive task, in this case, word-fragment completion, if previously exposed to the relevant information implicitly, opening up possible interventions aimed at this population.

Comparison of Diffusion Tensor Imaging Metrics in Normal-Appearing White Matter to Cerebrovascular Lesions and Correlation with Cerebrovascular Disease Risk Factors and Severity.

Alterations in tissue microstructure in normal-appearing white matter (NAWM), specifically measured by diffusion tensor imaging (DTI) fractional anisotropy (FA), have been associated with cognitive outcomes following stroke. The purpose of this study was to comprehensively compare conventional DTI measures of tissue microstructure in NAWM to diverse vascular brain lesions in people with cerebrovascular disease (CVD) and to examine associations between FA in NAWM and cerebrovascular risk factors. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured in cerebral tissues and cerebrovascular anomalies from 152 people with CVD participating in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). Ten cerebral tissue types were segmented including NAWM, and vascular lesions including stroke, periventricular and deep white matter hyperintensities, periventricular and deep lacunar infarcts, and perivascular spaces (PVS) using T1-weighted, proton density-weighted, T2-weighted, and fluid attenuated inversion recovery MRI scans. Mean DTI metrics were measured in each tissue region using a previously developed DTI processing pipeline and compared between tissues using multivariate analysis of covariance. Associations between FA in NAWM and several CVD risk factors were also examined. DTI metrics in vascular lesions differed significantly from healthy tissue. Specifically, all tissue types had significantly different MD values, while FA was also found to be different in most tissue types. FA in NAWM was inversely related to hypertension and modified Rankin scale (mRS). This study demonstrated the differences between conventional DTI metrics, FA, MD, AD, and RD, in cerebral vascular lesions and healthy tissue types. Therefore, incorporating DTI to characterize the integrity of the tissue microstructure could help to define the extent and severity of various brain vascular anomalies. The association between FA within NAWM and clinical evaluation of hypertension and disability provides further evidence that white matter microstructural integrity is impacted by cerebrovascular function.

The adverse effect of modifiable dementia risk factors on cognition amplifies across the adult lifespan.

Background: Reversible lifestyle behaviors (modifiable risk factors) can reduce dementia risk by 40%, but their prevalence and association with cognition throughout the adult lifespan is less well understood. Methods: The associations between the number of modifiable risk factors for dementia (low education, hypertension, hearing loss, traumatic brain injury, alcohol or substance abuse, diabetes, smoking, and depression) and cognition were examined in an online sample (N = 22,117, ages 18-89). Findings: Older adults (ages 66-89) had more risk factors than middle-aged (ages 45-65) and younger adults (ages 18-44). Polynomial regression revealed that each additional risk factor was associated with lower cognitive performance (equivalent to 3 years of aging), with a larger association as age increased. People with no risk factors in their forties to seventies showed similar cognitive performance to people 10 or 20 years younger with many risk factors. Interpretation: Modifiable dementia risk factors amplify lifespan age differences in cognitive performance.

A Cost-Benefit Analysis of a Group Memory Intervention for Healthy Older Adults with Memory Concerns.

This study examines whether memory intervention programs can mitigate health care costs. Research suggests these programs translate to a decreased intention of older adults who are worried about age-normal memory changes to seek traditional outlets for medical/psychiatric help. We employed a cost-benefit analysis approach to analyze the effectiveness of a memory intervention program within Ontario. We leveraged estimates of decreased intentionality to seek physician care following a community-based memory intervention with physician billing profiles to calculate the potential cost savings to the province's health care system. The intervention studied was found to reduce provincial health care spending by $6,094 per program group. This amount exceeds $121.25 in direct costs per attendee associated with administering five program sessions. This analysis justifies further research on how community-based memory and aging programs can offer low-cost solutions to help individuals cope with subjective memory complaints and assist the health care system in prioritizing care for aging patients.

Caregiving concerns and clinical characteristics across neurodegenerative and cerebrovascular disorders in the Ontario neurodegenerative disease research initiative.

OBJECTIVES: Caregiving burdens are a substantial concern in the clinical care of persons with neurodegenerative disorders. In the Ontario Neurodegenerative Disease Research Initiative, we used the Zarit's Burden Interview (ZBI) to examine: (1) the types of burdens captured by the ZBI in a cross-disorder sample of neurodegenerative conditions (2) whether there are categorical or disorder-specific effects on caregiving burdens, and (3) which demographic, clinical, and cognitive measures are related to burden(s) in neurodegenerative disorders? METHODS/DESIGN: N = 504 participants and their study partners (e.g., family, friends) across: Alzheimer's disease/mild cognitive impairment (AD/MCI; n = 120), Parkinson's disease (PD; n = 136), amyotrophic lateral sclerosis (ALS; n = 38), frontotemporal dementia (FTD; n = 53), and cerebrovascular disease (CVD; n = 157). Study partners provided information about themselves, and information about the clinical participants (e.g., activities of daily living (ADL)). We used Correspondence Analysis to identify types of caregiving concerns in the ZBI. We then identified relationships between those concerns and demographic and clinical measures, and a cognitive battery. RESULTS: We found three components in the ZBI. The first was "overall burden" and was (1) strongly related to increased neuropsychiatric symptoms (NPI severity r = 0.586, NPI distress r = 0.587) and decreased independence in ADL (instrumental ADLs r = -0.566, basic ADLs r = -0.43), (2) moderately related to cognition (MoCA r = -0.268), and (3) showed little-to-no differences between disorders. The second and third components together showed four types of caregiving concerns: current care of the person with the neurodegenerative disease, future care of the person with the neurodegenerative disease, personal concerns of study partners, and social concerns of study partners. CONCLUSIONS: Our results suggest that the experience of caregiving in neurodegenerative and cerebrovascular diseases is individualized and is not defined by diagnostic categories. Our findings highlight the importance of targeting ADL and neuropsychiatric symptoms with caregiver-personalized solutions.

Sex differences and modifiable dementia risk factors synergistically influence memory over the adult lifespan.

Introduction: More women than men develop Alzheimer's disease, yet women perform better and show less decline on episodic memory measures, a contradiction that may be accounted for by modifiable risk factors for dementia. Methods: Associations among age, sex, modifiable dementia risk factors, and cognition were measured in a cross-sectional online sample (n = 21,840, ages 18 to 89). Results: Across four tests of associative memory and executive functions, only a Face-Name Association task revealed sex differences in associative memory that varied by age. Men had worse memory than women (the equivalent of performing similar to someone 4 years older) across ages. Men had larger age differences than women (ie, worse memory in older ages) among people with no to one risk factor, but not those with multiple risk factors. Discussion: Because the relationship between dementia risk factors and age-related memory differences varies between men and women, sex-specific dementia prevention approaches are warranted.

An Agile Development Cycle of an Online Memory Program for Healthy Older Adults.

Online interventions for older adults should be tailored to their unique needs to increase the efficacy of and adherence to the intervention. The agile development cycle is a dynamic model to solicit and incorporate feedback from older adults during the design process. We combined this approach with the framework of Harvard University's clinical and translational phases that provide a clear structure for evaluating new health programs before they are offered in the community. We based our online memory program on the empirically validated in-person Memory and Aging Program. The aim of the present study was to combine the agile development cycle with the clinical and translational phases framework to develop and pilot an online memory program tailored to the unique needs of older adults. Study 1 involved piloting individual program modules on site and integrating participant feedback into the program's design to optimize usability. Study 2 involved two sequential pilots of the program accessed remotely to evaluate preliminary clinical outcomes and obtain feedback for iterative modifications. Plans for further validation and limitations are discussed. The successful application of the agile development cycle implemented in this series of studies can be adapted by others seeking to offer online content for targeted end users.

Evaluating the effectiveness of compensatory memory interventions in adults with acquired brain injury: A systematic review and meta-analysis of memory and everyday outcomes.

OBJECTIVE: Adults with acquired brain injury (ABI) often experience memory impairments that are persistent and difficult to treat. Although evidence has shown that rehabilitation programs may improve cognitive performance in persons with ABI, there is an opportunity to look more closely at the benefits provided by specific interventions. We conducted a systematic review and meta-analysis to evaluate whether compensation-based memory programs improve memory or everyday outcomes (e.g., mood, quality of life, community integration, everyday functioning). METHOD: The review was limited to published, English-language controlled trials that evaluated compensatory memory interventions for adults (18 +) with ABI using at least one memory or everyday outcome. The final search was conducted in April 2021 using PsychINFO, Medline, EMBASE, the Cochrane Review database, Google Scholar, and the reference lists of relevant articles. RESULTS: Of 2,817 identified articles, 22 controlled trials met inclusion criteria, of which 12 provided sufficient data to include in the meta-analyses. Risk of bias assessment identified problems with recruitment and masking procedures. Results indicate that compared to controls, these interventions produce positive effects on outcomes of immediate verbal recall (g = 0.43), participant-reported memory (g = 0.28), and strategy use (g = 0.39) and that these improvements are maintained at follow-up. CONCLUSIONS: Compensatory memory programs produce meaningful memory improvements and are a promising avenue for reducing ABI-related memory impairment. Future research focusing on specific subsets of ABI populations and a broader range of participant-reported outcomes is needed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neurocognitive Outcome Following Recovery from Severe Acute Respiratory Syndrome - Coronavirus-1 (SARS-CoV-1).

OBJECTIVE: Severe acute respiratory syndrome (SARS) is a highly contagious viral respiratory illness associated with hypoxia and dyspnea. Many of those who contracted and recovered from SARS during the 2002-2003 outbreak reported persistent physical, psychological, and cognitive difficulties. Here, we investigated the residual influences of SARS on cognition for a subset of healthcare professionals who recovered and were referred for neuropsychological evaluation through their workplace insurance. METHOD: Twenty-eight healthcare professionals were evaluated on neuropsychological and mood functioning approximately 1.5 years post-recovery from a severe respiratory illness. Test scores were compared with age-matched normative data, and correlations were examined between mood, self-report memory scales, subjective complaints (e.g., poor concentration, pain, fatigue), illness severity (i.e., length of hospitalization, oxygen use during hospital stay), and cognitive performance. RESULTS: Participants performed within age expectations on the majority of cognitive measures including overall memory ability. Although processing speed was generally within normal limits, 43% showed significant speed-accuracy trade-offs favoring accuracy over maintaining speed. Deficits were observed on measures of complex attention, such as working memory and the ability to sustain attention under conditions of distraction. Participants endorsed poorer memory ability than same-age peers on a meta-memory measure and mild to moderate depression and anxiety symptoms. Objective test performance was largely uncorrelated with self-reports, mood, or illness severity, except for moderate correlations between complex attention and participants' subjective ratings of Everyday Task-Oriented Memory. CONCLUSIONS: These findings demonstrate specific long-term cognitive deficits associated with SARS and provide further evidence of the cognitive effects of hypoxic illnesses.

Initiation and maintenance of behaviour change to support memory and brain health in older adults: A randomized controlled trial.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02087137.

When I'm 64: Age-Related Variability in Over 40,000 Online Cognitive Test Takers.

OBJECTIVES: Age-related differences in cognition are typically assessed by comparing groups of older to younger participants, but little is known about the continuous trajectory of cognitive changes across age, or when a shift to older adulthood occurs. We examined the pattern of mean age differences and variability on episodic memory and executive function measures over the adult life span, in a more fine-grained way than past group or life-span comparisons. METHOD: We used a sample of over 40,000 people aged 18-90 who completed psychometrically validated online tests measuring episodic memory and executive functions (the Cogniciti Brain Health Assessment). RESULTS: Cognitive performance declined gradually over adulthood, and rapidly later in life on spatial working memory, processing speed, facilitation (but not interference), associative recognition, and set shifting. Both polynomial and segmented regression fit the data well, indicating a nonlinear pattern. Segmented regression revealed a shift from gradual to rapid decline that occurred in the early 60s. Variability between people (interindividual variability or diversity) and variability within a person across tasks (intraindividual variability or dispersion) also increased gradually until the 60s, and rapidly after. Confirmatory factor analysis revealed a single general factor (of variance shared between tasks) offered a good fit for performance across tasks. DISCUSSION: Life-span cognitive performance shows a nonlinear pattern, with gradual decline over early and mid-adulthood, followed by a transition in the 60s to notably accelerated, but more variable, decline. Some people show less decline than others, and some cognitive abilities show less within-person decline than others.

Accuracy of a Self-Administered Online Cognitive Assessment in Detecting Amnestic Mild Cognitive Impairment.

OBJECTIVES: Our aim was to validate the online Brain Health Assessment (BHA) for detection of amnestic mild cognitive impairment (aMCI) compared to gold-standard neuropsychological assessment. We compared the diagnostic accuracy of the BHA to the Montreal Cognitive Assessment (MoCA). METHODS: Using a cross-sectional design, community-dwelling older adults completed a neuropsychological assessment, were diagnosed as normal cognition (NC) or aMCI, and completed the BHA and MoCA. Both logistic regression (LR) and penalized logistic regression (PLR) analyses determined BHA and demographic variables predicting aMCI; MoCA variables were similarly modeled. Diagnostic accuracy was compared using area under the receiver operating characteristic curve (ROC AUC) analyses. RESULTS: Ninety-one participants met inclusion criteria (51 aMCI, 40 NC). PLR modeling for the BHA indicated Face-Name Association, Spatial Working Memory, and age-predicted aMCI (ROC AUC = 0.76; 95% confidence interval [CI]: 0.66-0.86). Optimal cut-points resulted in 21% classified as aMCI (positive), 23% negative, and 56% inconclusive. For the MoCA, digits, abstraction, delayed recall, orientation, and age predicted aMCI (ROC AUC = 0.71; 95% CI: 0.61-0.82). Optimal cut-points resulted in 22% classified positive, 8% negative, and 70% inconclusive (LR results presented within). The BHA model classified fewer participants into the inconclusive category and more as negative for aMCI, compared to the MoCA model (Stuart-Maxwell p = .004). DISCUSSION: The self-administered BHA provides similar detection of aMCI as a clinician-administered screener (MoCA), with fewer participants classified inconclusively. The BHA has the potential to save practitioners time and decrease unnecessary referrals for a comprehensive assessment to determine the presence of aMCI.