Outcome Of Mild Cognitive Impairment Research Articles

Deep learning model for individualized trajectory prediction of clinical outcomes in mild cognitive impairment.

Accurately predicting when patients with mild cognitive impairment (MCI) will progress to dementia is a formidable challenge. This work aims to develop a predictive deep learning model to accurately predict future cognitive decline and magnetic resonance imaging (MRI) marker changes over time at the individual level for patients with MCI. We recruited 657 amnestic patients with MCI from the Samsung Medical Center who underwent cognitive tests, brain MRI scans, and amyloid-β (Aβ) positron emission tomography (PET) scans. We devised a novel deep learning architecture by leveraging an attention mechanism in a recurrent neural network. We trained a predictive model by inputting age, gender, education, apolipoprotein E genotype, neuropsychological test scores, and brain MRI and amyloid PET features. Cognitive outcomes and MRI features of an MCI subject were predicted using the proposed network. The proposed predictive model demonstrated good prediction performance (AUC = 0.814 ± 0.035) in five-fold cross-validation, along with reliable prediction in cognitive decline and MRI markers over time. Faster cognitive decline and brain atrophy in larger regions were forecasted in patients with Aβ (+) than with Aβ (-). The proposed method provides effective and accurate means for predicting the progression of individuals within a specific period. This model could assist clinicians in identifying subjects at a higher risk of rapid cognitive decline by predicting future cognitive decline and MRI marker changes over time for patients with MCI. Future studies should validate and refine the proposed predictive model further to improve clinical decision-making.

PLASMA BIOMARKERS FOR ALZHEIMER’S DISEASE AND RELATED NEUROPATHOLOGY IN RELATION TO MCI AND DEMENTIA: THE ARIC STUDY

Abstract Blood-biomarkers for Alzheimer’s Disease and related neuropathological processes, including amyloidosis, tau deposition, and neurodegeneration, may revolutionize the monitoring of risk and progression of neurocognitive outcomes in older adults. At visit 5 (2011-13) of the ARIC study, a multi-center longitudinal cohort study, amyloid-beta (Aβ42:Aβ40), ptau-181, glial fibrillary acidic protein (GFAP), and neurofilament light (NFL) were measured in plasma using an ultrasensitive single-molecule array (Simoa; Quanterix N4PE + p-tau-181 single-plex) in a sample of 1,711 participants (Age=76±5 years, 60% Female, 28% Black). Neurocognitive outcomes included adjudicated dementia and mild cognitive impairment (MCI) through 2019 for a median follow-up of 5.6 years. Multinomial logistic regressions estimated Relative Risk Ratios (RRR) of the four-category outcome of MCI (n=543), dementia (n=371), and death (n=59) vs. cognitively unimpaired (n=736) for each base(2) log-transformed biomarker, adjusted for age, sex, education, site-race, hypertension, diabetes, BMI, APOE, and eGFR. When estimates appeared similar for MCI and dementia, an additional analysis modeled RRR of a three-category outcome of combined MCI/dementia, death, and cognitively unimpaired. Higher plasma Aβ42:Aβ40 ratio was associated with lower MCI/dementia risk (RRR=0.48, 95%CI: 0.32,0.73). Higher levels of all other biomarkers were associated with higher risk of MCI [p-tau181 (RRR=1.57, 95%CI: 1.23,2.00); GFAP (RRR=1.31, 95%CI: 1.03,1.67); NFL (RRR=1.64, 95%CI: 1.26,2.13)] and dementia [p-tau181 (RRR=3.16, 95%CI: 2.43,4.11); GFAP (RRR=2.40, 95%CI: 1.80,3.20); NFL (RRR=3.62, 95%CI: 2.58,5.09)]. These results indicate blood-biomarkers representative of multiple neuropathological processes were strongly associated with both MCI and all-cause dementia outcomes, emphasizing their potential role as tools in risk identification, early diagnosis, and possibly guiding interventions.

Impact of Multivitamin‐Mineral and Cocoa Extract on Incidence of Mild Cognitive Impairment and Dementia: Results from the Cocoa Supplement and Multivitamin Outcomes Study for the Mind COSMOS‐Mind

AbstractBackgroundCOSMOS‐Mind, a large, randomized placebo‐controlled pragmatic trial in older adults, recently reported that daily supplementation with multivitamin‐mineral, but not cocoa extract, benefited global cognition. We assessed effects of these supplements on prespecified secondary outcomes of mild cognitive impairment (MCI) and all‐cause dementia (DM). We also assessed treatment‐related cognitive trajectories leading to conversion to MCI or dementia.MethodCOSMOS‐Mind (N = 2262) administered a telephone‐based cognitive battery at baseline and annually for 3 years. Proxies of participants meeting criteria for suspected cognitive impairment based on a cognitive screener (TICSm) were interviewed. An expert panel adjudicated cognitive status. Incidence rates of MCI, and separately DM, were compared among arms with proportional hazards regression. Changes in cognitive trajectories leading to MCI and DM were assessed with linear models.ResultAt baseline, adjudication for suspected cognitive impairment was triggered for 419 (20%) participants, yielding adjudications of 217 (10%) MCI and 4 (0.2%) DM cases. During follow‐up, triggers were less frequent in the MVM than placebo arms: hazard ratio = 0.73 (p = 0.04). Across 3 years, 110 incident MCI and 14 incident DM cases were adjudicated. Incidence rates of these outcomes did not vary by assignment to multivitamin‐mineral or cocoa extract (all p≥0.05), however statistical power was low. Incident MCI was associated with a marked decline in cognitive function from the previous year (p<0.001). When participants assigned to multivitamin‐mineral versus placebo converted to MCI, their scores for global cognition (p = 0.03) and executive function (p<0.001) were higher and had declined less relative to the previous year (p = 0.03 for global cognition; p = 0.004 for executive function). Daily cocoa extract use did not attenuate cognitive decline leading up to MCI.ConclusionCOSMOS‐Mind does not provide evidence that cocoa extract or multivitamin‐mineral therapy lowers risk of incident MCI or DM. Multivitamin‐mineral therapy, but not cocoa extract, may provide cognitive resilience countering conversion to MCI.

Systolic Blood Pressure Levels and Probable Dementia : Secondary Analysis of a Randomized Clinical Trial

AbstractBackgroundDespite a significant 19% reduction in risk for mild cognitive impairment, the primary Systolic Blood Pressure Intervention Trial (SPRINT) analysis lacked sufficient evidence to assert statistical significance for the 17% reduction in probable dementia alone in intensive blood pressure (BP) control, defined as a target systolic BP < 120 mmHg, compared to the standard target of < 140 mmHg (p = 0.10). However, early termination of SPRINT may have caused these analyses to be under‐powered. We applied the statistical framework of joint models for longitudinal data and time‐to‐event outcomes to analyze the effect of systolic BP levels on probable dementia using the SPRINT data.MethodsSPRINT was a multicenter randomized clinical trial that enrolled patients ≥50 years of age with hypertension and increased cardiovascular risk but without diabetes or history of stroke. In this secondary analysis, the primary outcome was occurrence of adjudicated probable dementia after randomization. Secondary outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia. To analyze these outcomes, we applied joint longitudinal and survival models. In the longitudinal component of the joint model, systolic BP levels were modeled as a quadratic function of time since randomization, accounting for correlation in repeated measurements and for assignment to intensive BP control versus standard care. In the survival component, multi‐variable adjustment for race, education, and age at baseline was applied.ResultsOver a median follow up of 5.2 years, a total of 325 probable dementia and 640 mild cognitive impairment events occurred. After multi‐variable adjustment (as above), the hazard ratio per 10 mmHg decrease in systolic BP was 0.89 (95% confidence interval [CI] 0.79, 0.99) for probable dementia, 0.89 (95% CI 0.82, 0.96) for mild cognitive impairment, and 0.90 (95% CI 0.84, 0.97) for their composite outcome (Table). Dynamic predictions after 2 years of follow‐up provide a descriptive summary of systolic BP levels and predicted risk of probable dementia or mild cognitive impairment (Figure).ConclusionReducing systolic BP decreases the risk of both probable dementia and mild cognitive impairment.

Predictive value of BMI in Cognitive Outcome in Mild Cognitive Impairment

AbstractBackgroundThis study aimed to determine the association between neuropsychological performance and body mass index (BMI) in patients with mild cognitive impairment (MCI). In addition, this study investigated the effects of the APOE genotype and sex in the relationship between the BMI and cognition in MCI.MethodsA total of 3,038 subjects with MCI aged 65‐90 were enrolled from the Clinical Research Center for Dementia of South Korea (CREDOS) cohort and a dementia cohort of the Ewha Womans University Mokdong Hospital (EUMC). MCI patients were classified into three subgroups (normal‐weight, overweight and obesity) according to the Asian standard of BMI. Cognitive performances between groups were compared by one way analysis of variance. To investigate the effects of the age, education, APOE genotype and sex, multivariate linear regression models after adjusting for possible confounders were used.ResultsEven‐though normal BMI groups were younger, had more males and less comorbidities, higher BMI groups (Overweigh and Obese) were associated with better performance in cognitive functions, scores of all neurocognitive tests were significantly increased (RCFT copy, p = 0.047; animal fluency, p = 0.039; phonemic fluency, p = 0.013; SVLT delay recall, p = 0.005; RCFT delay recall, K‐MMSE, p = 0.001; K‐BNT and Stroop test, p<0.001), and CDR‐SB (p = 0.001) was decreased. The APOE ε4 carriers showed positive relationship between the BMI and the memory tasks: SVLT delay recall (p = 0.017) and RCFT delay recall (p = 0.002). And comparing between APOE ε4 carrier gender groups, significant positive relationship was shown only with visual memory task as BMI increases.ConclusionsOur findings suggested that higher BMI in patients with MCI were associated with better cognitive performance. The effects of the APOE genotype and sex in the associations between BMI and cognition were distinguishing. Therefore, according to physical status, APOE ε4 genotype, and sex‐specific strategies in the assessments and treatments may be necessary in elderly patients with MCI.

SLEEP MICROARCHITECTURE IN MILD COGNITIVE IMPAIRMENT: A HIGH‐DENSITY EEG STUDY

AbstractBackgroundSleep disturbance and sleep disorders are potential risk factors for dementia. Adults with mild cognitive impairment (MCI) are at increased risk of developing dementia and many report disturbed sleep. Altered sleep neurophysiology including deficits in sleep spindles and slow wave activity (SWA) during NREM sleep have been reported in MCI, though studies are sparse. These NREM EEG oscillations are crucial for overnight memory consolidation and optimal daytime functioning. Abnormal EEG activity during sleep in MCI may adversely impact sleep‐dependent memory processes and cognitive trajectory. This study is the first to examine sleep microarchitecture using high‐density EEG technology in MCI.MethodOlder adults with multi‐domain MCI (n = 19, mean age 68.5 years) and cognitively‐intact controls (n = 22, 69 years) had 256‐channel high‐density EEG recordings during overnight polysomnography and resting wakefulness. Declarative (word paired associates) and procedural (finger tapping) memory tasks were administered before and after sleep. Neuropsychological testing and brain MRI scans were also performed. After artefact processing, spectral analysis was performed for high‐density EEG recordings. Topographical power maps were calculated for standard frequency ranges for NREM sleep (N2 and N3 (slow wave sleep)). Maps were compared between groups using normalized power (z‐scores computed for each subject).ResultThe MCI group had worse declarative (% retention, MCI vs Controls: 84.2 ± 16.6 vs. 94.5 ± 7.8, p = 0.024) and procedural (% early improvement: 92.9 ± 11.0 vs. 103.0 ± 12.0%, p = 0.017) overnight memory consolidation than the controls. Topographic analysis of high‐density EEG data revealed a regional increase in SWA (1‐4.5Hz) EEG power during N3 in a cluster of 18 electrodes overlying the centroparietal cortex in the MCI group (cluster mean t‐value = 3.11, p = 0.0036, uncorrected) and a regional reduction in SWA in the left frontal (5 channels, t = ‐3.75, p<0.001) and right temporal areas (5 channels, t = ‐3.46, p = 0.001), Figure 1.ConclusionOvernight memory consolidation was impaired in this MCI population. Regional differences in SWA during deep sleep were present in distinct brain regions and may indicate pathology. Future analysis exploring associations between EEG abnormalities with underlying brain structures may provide mechanistic insights into the impact of altered sleep neurophysiology on cognitive outcomes in MCI.

Middle Age Prevention of Future Alzheimer’s Disease and Related Dementias with Intensive Treatment of Hypertension: Middle PATH Clinical Trial Proposal

AbstractStrong epidemiological evidence from multiple studies suggests that elevated systolic blood pressure (SBP) in midlife is a risk factor for Alzheimer’s disease and Related Dementias (ADRD) later in life. The most common neuropathology of biomarker‐confirmed AD is combined AD neuropathological changes and cerebrovascular disease. Hypertension is a leading cause of cerebrovascular disease. The SPRINT MIND trial demonstrated that a goal SBP<120 mm Hg reduced risk for combined mild cognitive impairment (MCI) and dementia by 15% in older individuals compared to a goal SBP<140 mm Hg. SBP can be safely treated with inexpensive medications. Despite being potentially safe and cost‐effective, with strong supporting evidence for benefit, intensive SBP lowering in midlife to reduce future ADRD risk has never been studied, likely because clinical outcomes of MCI and dementia are not practical in this age range in a trial that is usually limited to about 5 years. Elevated SBP is a major risk factor for white matter hyperintensity volume (WMHV) accumulation, an MRI marker with extensive evidence demonstrating this to be associated with and predictive of incident ADRD, making WMHV a suitable surrogate outcome for the initial trial period. While we acknowledge the challenges of using a surrogate outcome, there is no suitable alternative when testing interventions to lower future ADRD risk starting in middle age, a strategy that we believe is essential. The Alzheimer’s Prevention Initiative and Wake Forest have formed a collaboration to investigate the effect of goal SBP<120 mm Hg compared to the SBP achieved by enhanced usual care (SBP = 135 mm Hg) on annualized rate of WMHV accumulation in persons ages 45‐65 who have some existing vascular risk at baseline. Secondary outcomes of changes in AD blood biomarkers and relevant cognitive test scores will help elucidate whether and how SBP and AD are interactive or independent deleterious pathophysiological processes. The intention, should the initial phase prove successful, is to continue and expand the trial until a clinical benefit can definitively be assessed.

Middle Age Prevention of Future Alzheimer’s Disease and Related Dementias with Intensive Treatment of Hypertension: Middle PATH Clinical Trial Proposal

AbstractStrong epidemiological evidence from multiple studies suggests that elevated systolic blood pressure (SBP) in midlife is a risk factor for Alzheimer’s disease and Related Dementias (ADRD) later in life. The most common neuropathology of biomarker‐confirmed AD is combined AD neuropathological changes and cerebrovascular disease. Hypertension is a leading cause of cerebrovascular disease. The SPRINT MIND trial demonstrated that a goal SBP<120 mm Hg reduced risk for combined mild cognitive impairment (MCI) and dementia by 15% in older individuals compared to a goal SBP<140 mm Hg. SBP can be safely treated with inexpensive medications. Despite being potentially safe and cost‐effective, with strong supporting evidence for benefit, intensive SBP lowering in midlife to reduce future ADRD risk has never been studied, likely because clinical outcomes of MCI and dementia are not practical in this age range in a trial that is usually limited to about 5 years. Elevated SBP is a major risk factor for white matter hyperintensity volume (WMHV) accumulation, an MRI marker with extensive evidence demonstrating this to be associated with and predictive of incident ADRD, making WMHV a suitable surrogate outcome for the initial trial period. While we acknowledge the challenges of using a surrogate outcome, there is no suitable alternative when testing interventions to lower future ADRD risk starting in middle age, a strategy that we believe is essential. The Alzheimer’s Prevention Initiative and Wake Forest have formed a collaboration to investigate the effect of goal SBP<120 mm Hg compared to the SBP achieved by enhanced usual care (SBP≥135 mm Hg) on annualized rate of WMHV accumulation in persons ages 45‐65 who have some existing vascular risk at baseline. Secondary outcomes of changes in AD blood biomarkers and relevant cognitive test scores will help elucidate whether and how SBP and AD are interactive or independent deleterious pathophysiological processes. The intention, should the initial phase prove successful, is to continue and expand the trial until a clinical benefit can definitively be assessed.

The Efficacy of Cognitive Training on Neuropsychological Outcomes in Mild Cognitive Impairment: A Meta-Analysis.

Mild cognitive impairment (MCI) or mild neurocognitive disorder is an intermediate stage of cognitive impairment between normal cognitive aging and dementia. Given the absence of effective pharmacological treatments for MCI, increasing numbers of studies are attempting to understand how cognitive training (CT) could benefit MCI. This meta-analysis aims to update and assess the efficacy of CT on specific neuropsychological test performance (global cognitive functioning, short-term verbal memory, long-term verbal memory, generativity, working memory, and visuospatial abilities) in individuals diagnosed with MCI, as compared to MCI control groups. After searching electronic databases for randomized controlled trials, 31 studies were found including 2496 participants. Results showed that CT significantly improved global cognitive functioning, short-term and long-term verbal memory, generativity, working memory, and visuospatial abilities. However, no significant effects were observed for shifting, abstraction ability/concept formation, processing speed, and language. The mode of CT had a moderating effect on abstraction ability/concept formation. The findings provide specific insights into the cognitive functions influenced by CT and guide the development of tailored interventions for MCI. While CT holds promise, further research is needed to address certain cognitive deficits and assess long-term effects on dementia progression.

Hippocampal adaptations in Mild Cognitive Impairment patients are modulated by bilingual language experiences

AbstractBilingualism has been shown to contribute to increased resilience against cognitive aging. One of the key brain structures linked to memory and dementia symptom onset, the hippocampus, has been observed to adapt in response to bilingual experience – at least in healthy individuals. However, in the context of neurodegenerative pathology, it is yet unclear what role previous bilingual experience might have in terms of sustaining integrity of this structure or related behavioral correlates. The present study adds to the limited cohort of research on the effects of bilingualism on neurocognitive outcomes in Mild Cognitive Impairment (MCI) using structural brain data. We investigate whether bilingual language experience (operationalized as language entropy) results in graded neurocognitive adaptations within a cohort of bilinguals diagnosed with MCI. Results reveal a non-linear effect of bilingual language entropy on hippocampal volume, although they do not predict episodic memory performance, nor age of MCI diagnosis.

Dietary pattern, food, and nutritional supplement effects on cognitive outcomes in mild cognitive impairment: a systematic review of previous reviews.

Nutritional interventions may benefit cognition in people with mild cognitive impairment (MCI). However, evidence is yet to be synthesized in a way that can inform recommendations for clinical and public health settings. To systematically review evidence on the effect of dietary patterns, foods, and nutritional supplements on cognitive decline in individuals with MCI. Guided by the Preferred Reporting items for Systematic Review and Meta-Analysis Protocols 2015 statement, the Medline, EMBASE, and CINAHL databases, the JBI Database of Systematic Reviews and Implementation Reports, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects were searched (publication years 2005 to 2020). Included studies were English-language systematic reviews and meta-analyses of randomized controlled trials and cohort studies reporting on the effectiveness of nutritional interventions on cognition of individuals with MCI. Two reviewers independently selected studies and extracted data on cognitive outcomes and adverse events. Review quality was assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews-2). Primary study overlap was managed following Cochrane Handbook guidelines. Of the 6677 records retrieved, 20 reviews were included, which, in turn, reported on 43 randomized controlled trials and 1 cohort study that, together, addressed 18 nutritional interventions. Most reviews were limited by quality and the small number of primary studies with small sample sizes. Reviews were mostly positive for B vitamins, omega-3 fatty acids, and probiotics (including 12, 11 and 4 primary studies, respectively). Souvenaid and the Mediterranean diet reduced cognitive decline or Alzheimer's disease progression in single trials with <500 participants. Findings from studies with a small number of participants suggest vitamin D, a low-carbohydrate diet, medium-chain triglycerides, blueberries, grape juice, cocoa flavanols, and Brazil nuts may improve individual cognitive subdomains, but more studies are needed. Few nutritional interventions were found to convincingly improve cognition of individuals with MCI. More high-quality research in MCI populations is required to determine if nutritional treatments improve cognition and/or reduce progression to dementia. Open Science Framework protocol identifier DOI:10.17605/OSF.IO/BEP2S.

Metabolic syndrome biomarkers relate to rate of cognitive decline in MCI and dementia stages of Alzheimer’s disease

BackgroundThe relationship between biomarkers of metabolic syndrome and insulin resistance, plasma triglyceride/HDL cholesterol (TG/HDL-C) ratio, on the rate of cognitive decline in mild cognitive impairment (MCI) and dementia stages of Alzheimer’s disease (AD) is unknown. The role of peripheral and cerebrospinal fluid (CSF) levels of Apolipoprotein A1 (ApoA1), a key functional component of HDL, on cognitive decline also remains unclear among them. Here we evaluate baseline plasma TG/HDL-C ratio and CSF and plasma ApoA1 levels and their relation with cognitive decline in the MCI and Dementia stages of AD.Patients and methodsA retrospective longitudinal study (156 participants; 106 MCI, 50 AD dementia) from the Alzheimer’s Disease Neuroimaging Initiative, with an average of 4.0 (SD 2.8) years follow-up. Baseline plasma TG/HDL-C, plasma, and CSF ApoA1 and their relationship to inflammation and blood–brain barrier (BBB) biomarkers and longitudinal cognitive outcomes were evaluated. Multivariable linear mixed effect models were used to assess the effect of baseline analytes with longitudinal changes in Mini-Mental State Exam (MMSE), Clinical Dementia Rating–Sum of Boxes (CDR-SB), and Logical Memory delayed recall (LM) score after controlling for well-known covariates.ResultsA total of 156 participants included 98 women, 63%; mean age was 74.9 (SD 7.3) years. At baseline, MCI and dementia groups did not differ significantly in TG/HDL-C (Wilcoxon W statistic = 0.39, p = 0.39) and CSF ApoA1 levels (W = 3642, p = 0.29), but the dementia group had higher plasma ApoA1 than the MCI group (W = 4615, p = 0.01). Higher TG/HDL-C ratio was associated with faster decline in CDR-SB among MCI and dementia groups. Higher plasma ApoA1 was associated with faster decline in MMSE and LM among MCI, while in contrast higher CSF ApoA1 levels related to slower cognitive decline in MMSE among MCI. CSF and plasma ApoA1 also show opposite directional correlations with biomarkers of BBB integrity. CSF but not plasma levels of ApoA1 positively correlated to inflammation analytes in the AGE-RAGE signaling pathway in diabetic complications (KEGG ID:KO04933).ConclusionsBiomarkers of metabolic syndrome relate to rate of cognitive decline among MCI and dementia individuals. Elevated plasma TG/HDL-C ratio and plasma ApoA1 are associated with worse cognitive outcomes in MCI and dementia participants. CSF ApoA1 and plasma ApoA1 likely have different roles in AD progression in MCI stage.

Do service-users find the outcome of Mild Cognitive Impairment useful? A summary of Blatchford &amp; Cook’s (2020) systematic review

Mild Cognitive Impairment (MCI) is a common outcome following assessment of suspected dementia. However, it is unclear whether service-users perceive that being made aware is beneficial. The term itself is nebulous in terms of prognostic certainty and its utility for guiding interventions. This article summarises the systematic review conducted by Blatchford and Cook (2020) exploring research focused on service-users experiences of receiving the outcome of MCI and the impact of this upon them and their care partners. Service-user and care partner perspectives were shaped by the quality of information and support provided, and several factors shaped their experiences of being informed, including: personal perceptions and experiences, coping styles and living circumstance. The results suggested that clear information and quality support, tailored to service-user needs may improve the utility of the MCI outcome for service-users. The summary concludes by providing suggestions for enhancing service provision.

Association of circadian rhythm with mild cognitive impairment among male pneumoconiosis workers in Hong Kong: a cross-sectional study

Weakened circadian activity rhythms (CARs) were associated with mild cognitive impairment (MCI) in the general population. However, it remains unclear among pneumoconiosis patients. We aimed to address this knowledge gap. This cross-sectional study comprised 186 male pneumoconiosis patients (71.3 ± 7.8 years) and 208 healthy community men. Actigraphy was used to determine CARs parameters (percent rhythm, amplitude, MESOR, and acrophase). Values below the corresponding medians of the CARs parameters represented weakened CARs. The Cantonese version of Mini-Mental State Examination (CMMSE) was used to assess cognitive function, MCI, and the composite outcome of MCI plus cognitive impairment. Compared with the community referents, pneumoconiosis patients had worse cognition and dampened CARs. Compared with the community referents or pneumoconiosis patients with robust circadian rhythm, pneumoconiosis patients with weakened circadian rhythm were consistently associated with increased risk of MCI and the composite outcome. However, significant association was only observed between MESOR and the composite outcome (adjusted OR = 1.99, 95%: 1.04–3.81). A delayed phase of CARs was insignificantly associated with MCI and the composite outcome. Our findings showed that weakened CARs were associated with worse cognitive function among male pneumoconiosis workers. Intervention in improving CARs may mitigate cognitive deterioration in male pneumoconiosis workers.

S-02-3: A REVIEW AND NEW INSIGHTS FROM THE SPRINT MIND TRIAL DATA

Background: Proven treatments for reducing the risk of mild cognitive impairment (MCI) and dementia have been lacking. The impact of intensive treatment of hypertension on the incidence of Mild Cognitive Impairment (MCI) and dementia was tested in the Systolic Blood Pressure Intervention Trial (SPRINT-MIND) by prospectively assessing the effect of intensive blood pressure control to a target systolic blood pressure of &lt;120 mmHg versus a standard target (&lt;140 mmHg). This presentation reviews the SPRINT results demonstrating a reduction in risk of developing dementia and MCI and presents additional data on the reliability of the MCI and dementia diagnosis. We will also provide preliminary evidence for differential cognitive benefit from specific antihypertensive medicines and evidence for lack of benefit after onset of cognitive impairment Results: At one year, mean systolic blood pressure was 121.4 mmHg in the intensive-treatment group and 136.2 mmHg in the standard-treatment group. Treatment was stopped on 8/20/2015 due to CVD benefit after a median follow up of 3.26 years, but cognitive assessment continued. Participant mean age was 67.9 years (35.6% women) and 8,626 (92.1%) completed at least one follow-up cognitive assessment. There was a significantly lower rate of adjudicated incident MCI (HR 0.81, CI 0.67–0.97) and a non-significant reduction in probable dementia (HR 0.83, CI 0.69–1.04). The combined outcome of MCI plus probable all cause dementia was significantly lower (HR 0.85, CI 0.74–0.97) in the intensive versus standard treatment group. Most cases occurred in persons over age 70. At 2 years, MCI classification was 10X more likely to transition to dementia than normal cognition and 30% of classified as MCI reverted to normal, consistent with other large epidemiologic studies of MCI trajectory Conclusions: Among ambulatory adults at increased risk for CVD but without diabetes, treating to a SBP target &lt; 120 mmHg compared to a target of &lt; 140 mmHg reduces the risk of incident MCI and combined MCI/probable dementia. Reduction of dementia risk by cardiovascular interventions is feasible in the elderly population.

Brain energy rescue with ketones improves cognitive outcomes in MCI

AbstractBackgroundAn emerging strategy to delay the onset of Alzheimer disease (AD) is to use ketones to overcome the progressive brain energy deficit caused by deteriorating brain glucose metabolism in mild cognitive impairment (MCI). Ketones (acetoacetate and beta‐hydroxybutyrate) are the brain’s main alternative fuel to glucose; in contrast to glucose, ketone metabolism by the brain is now known to be unaffected in MCI and AD. Successful brain energy rescue with ketones in MCI was recently reported.MethodsIn the 6‐month, randomized, placebo‐controlled Benefic Trial (NCT02551419), the active arm was a ketogenic medium chain triglyceride (kMCT) supplement in a lactose‐free skim milk emulsion (15 g kMCT twice/day; n = 39 completers). The placebo arm was a non‐ketogenic iso‐energetic vegetable oil (n = 44 completers). Brain ketone and glucose metabolism were assessed by PET.ResultsPerformance on all five cognitive domains improved significantly over 6 months in the kMCT group: (i) Episodic memory (trial 1, Free and Cued Recall Test) increased by 1 word (+0.5 Δ Z‐score); (ii) Executive function (Verbal Fluency Test) correct answers increased by 2 words (+0.3 Δ Z‐score) but decreased by 1 word on placebo (‐0.1 Δ Z‐score), time taken on the Stroop Colour Naming Test decreased by 1 sec (p = 0.09), and errors on the Trail Making Test increased by 0.8 on placebo (p = 0.02); (iii) Language (Boston naming test) correct answers increased by 1.3 words. (iv) Processing speed increased directly with higher brain ketone uptake in several white matter tracts. (v) Improved attention was directly associated with increased ketone uptake and functional connectivity in the dorsal attention network.ConclusionsImproved cognition correlating positively with improved brain energy supply by ketones suggests a direct link to brain energy status. The moderate effect size of this kMCT intervention indicates a clinically meaningful benefit on certain cognitive outcomes, some of which relate directly to risk of MCI progressing to AD. Other potential ketogenic interventions that have been less well studied in MCI or AD include a ketogenic diet and ketone salts or esters. Whether brain energy rescue with ketones can delay the onset or progression of AD should now be assessed.

Associations of Atrial Fibrillation with Mild Cognitive Impairment and Dementia: An Investigation Using SPRINT Research Materials.

Background: Atrial fibrillation (AF) is linked to increased risk of dementia and cognitive decline, but whether AF and its ascertainment methods affect cognition in patients with hypertension has received less attention. Methods: We studied 8469 participants with elevated systolic blood pressure who were free of stroke and diabetes at baseline enrolled in the Systolic Blood Pressure Intervention Trial. AF was ascertained using three approaches: self-report of AF, AF from a safety event, and study electrocardiogram-determined (ECG) AF. Mild cognitive impairment (MCI) and probable dementia (PD) were ascertained from in-person assessments or telephone interviews from the participant or an informant. We used Cox proportional hazard models to estimate hazard ratios for the association of AF (all three sources) with outcomes of MCI, PD, and a composite MCI/PD outcome. Results: During a mean follow-up of 4.6 years, 974 (12%) participants had AF (prevalent or incident), 634 were diagnosed with MCI, and 316 with PD. When comparing those with AF (from any source) to those without, no differences were detected in the risk of MCI or PD. Comparison between AF sources found ECG-AF to be associated with an elevated risk of MCI/PD (hazard ratio (HR) 1.59, 95% confidence interval (95%CI) 1.06, 2.38). Neither AF ascertained through safety events nor self-reported AF were associated with MCI or PD. Conclusion: The association of AF with incidence of MCI/PD differed by method of AF ascertainment. Case definition of AF and quantification of AF burden are important factors in studies evaluating the link between AF and cognitive dysfunction.

The Associations Between Cardiorespiratory Fitness, Hippocampal Health, And Cognition In Mild Cognitive Impairment

Mild cognitive impairment (MCI), a prodromal stage of Alzheimer’s disease, has negative effects on cognition and is associated with structural changes in the brain, particularly the hippocampus. We utilized magnetic resonance elastography (MRE), an imaging technique that estimates brain mechanical properties, to quantify the integrity of the underlying tissue microstructure. MRE is an emerging method for evaluating hippocampal health and its relation to cognition. We used MRE to assess the relationship between aerobic fitness and hippocampal integrity in MCI and aging, as fitness is a modifiable lifestyle factor. Establishing these links can help identify those at risk of cognitive impairment and establish interventions. PURPOSE: To demonstrate the value of MRE measures of hippocampal health to assess the relationship between aerobic fitness, cognition, and MRE in MCI. METHODS: We recruited 47 healthy older adults (69 ± 6 yrs) and 13 with amnestic MCI (72 ± 9 yrs). Participants had an MRI, fitness and cognitive testing to collect hippocampal stiffness and damping ratio, reflecting the resistance of tissue, relative VO2,max, and a composite cognitive score. RESULTS: Older adults had significantly higher stiffness (p < .01) and lower damping ratio (p = .001). Stiffness significantly mediated the relationship between diagnosis and cognition (Estimated indirect effect, ACME (95% CI) = .04 (-.004, -.009)). VO2 was differentially associated with MRE measures in MCI compared healthy older adults. A significant diagnosis x fitness interaction effect was observed (Stiffness: β = .012, SE = .006, p = .041; Damping ratio: β = -.001, SE = .001, p = .041), with a stronger relationship between VO2 and MRE measures in the MCI group (Stiffness: p = .029, 95% CI = .075, .881; Damping ratio: p = .243, 95% CI = -.74, .33) compared to in the healthy older group (Stiffness: p = .191, 95% CI = -1.01, .49; Damping ratio: p = .764, 95% CI = -.36, .27). Only stiffness was associated with fitness in MCI participants. CONCLUSIONS: These preliminary findings suggest the utility of MRE in studying the mechanism of disease, with stiffness mediating the relationship between groups and cognition. Fitness is related to MRE outcomes in MCI, specifically stiffness, suggesting that higher aerobic fitness may be even more beneficial for those with MCI.

Mindfulness-Based Training Does Not Improve Neuropsychological Outcomes in Mild Cognitive Impairment More Than Spontaneous Reversion Rates: A Randomized Controlled Trial.

Current pharmacological and behavioral treatment options for mild cognitive impairment (MCI) are limited, motivating a search for alternative therapies that might slow the progression of cognitive decline. We investigated the effectiveness of a cognition-focused mindfulness-based intervention. An open-label, three arm randomized controlled trial was conducted at a public tertiary medical center. Older persons (ages 45-75; N = 76) diagnosed with MCI were recruited and randomized into either mindfulness-based training (MBT), cognitive rehabilitation therapy (CRT), or treatment as usual (TAU). Participants in the intervention arms received 8 weekly 2-h sessions delivered in a group setting and engaged in home practice. Primary outcomes measures included changes in index scores for attention, immediate memory, and delayed memory as measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Depression was a secondary outcome. Using intent-to-treat analysis, we found that participants receiving MBT showed significant improvements in global cognition (d = 0.26; [95%CI 0.03-0.56]) and delayed memory (d = 0.36; [95%CI 0.17-0.57]), with significantly greater improvements in delayed memory than CRT (ηp2 = 0.10). However, there was no benefit of MBT over TAU. No change in depression was observed in the MBT group. Reductions in depression were associated with improvements in cognitive functioning in the MBT group only. Our results suggest that a cognition-focused MBT did not improve cognitive functioning in MCI patients substantially more than spontaneous reversion rates, possibly as mood symptoms were not significantly alleviated in this group.

Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults

BackgroundThe neurocognitive effect of statins in older adults remain uncertain. ObjectivesThe aim of this study was to investigate the associations of statin use with cognitive decline and incident dementia among older adults. MethodsThis analysis included 18,846 participants ≥65 years of age in a randomized trial of aspirin, who had no prior cardiovascular events, major physical disability, or dementia initially and were followed for 4.7 years. Outcome measures included incident dementia and its subclassifications (probable Alzheimer’s disease, mixed presentations); mild cognitive impairment (MCI) and its subclassifications (MCI consistent with Alzheimer’s disease, other MCI); and changes in domain-specific cognition, including global cognition, memory, language and executive function, psychomotor speed, and the composite of these domains. Associations of baseline statin use versus nonuse with dementia and MCI outcomes were examined using Cox proportional hazards models and with cognitive change using linear mixed-effects models, adjusting for potential confounders. The impact of statin lipophilicity on these associations was further examined, and effect modifiers were identified. ResultsStatin use versus nonuse was not associated with dementia, MCI, or their subclassifications or with changes in cognitive function scores over time (p > 0.05 for all). No differences were found in any outcomes between hydrophilic and lipophilic statin users. Baseline neurocognitive ability was an effect modifier for the associations of statins with dementia (p for interaction < 0.001) and memory change (p for interaction = 0.02). ConclusionsIn adults ≥65 years of age, statin therapy was not associated with incident dementia, MCI, or declines in individual cognition domains. These findings await confirmation from ongoing randomized trials.