Incident Mild Cognitive Impairment Research Articles

Does periodontitis have any association with mild cognitive impairment?

This study aimed at determining the association between periodontitis and mild cognitive impairment. For this, different electronic databases, including PubMed, Scopus, Embase and Web of Science, were searched for finding the relevant literature. In addition, hand searching of relevant journals was also done to find gray literature. The systematic review included observational studies only. Accordingly, case-control, cohort and cross-sectional studies were searched. The search strategy was based on PECO framework, wherein the studies which included patients with/without periodontitis and patients with/without mild cognitive impairment (MCI)were included. A total of 7 studies were included and the data from these studies and the data including bibliographic details, demographic data, data about periodontitis, presence of MCI etc. was extracted from the included articles. The extracted data, was then assessed for heterogeneity using clinical parameters and I2 statistical test. Owing to low heterogeneity, fixed-effects model was used for meta-analysis. Meta-analysis was done to determine the association between periodontitis and MCI and significantly higher incidence of MCI was found in patients with periodontitis OR = OR, 1.70 (95% CI: 1.24-2.32, p < 0.001). A subgroup analysis was done by including the studies comparing incidence of MCI in patients with severe periodontitis, which resulted in even stronger association with an OR of 2.09 (95% CI: 1.49-2.92, p < 0.001). Lastly, periodontal parameters, including CAL, PPD, and PI were compared amongst patients with/without MCI. Significant differences were observed for both CAL and PI, with worsening of values in patients with MCI. Observed mean difference for CAL and PI were 0.44 (95% CI: 0.12-0.75) and 0.72 (95% CI:0.50-0.93), respectively. NS differences were observed for PPD values with a mean difference of 0.21 and 95% CI as -0.08 to 0.49. Strong association between periodontitis and MCI was observed, indicating periodontitis to be a risk factor for MCI.

Meta-analysis on the interrelationship between sarcopenia and mild cognitive impairment, Alzheimer's disease and other forms of dementia.

Sarcopenia has been associated with adverse health outcomes, including cognitive dysfunction. However, its specific interrelationship with neurocognitive disorders such as mild cognitive impairment (MCI), Alzheimer's disease (AD) or other types of dementia has not been thoroughly explored. This meta-analysis aims to summarize the existing evidence on this interrelationship. This systematic review was pre-registered on PROSPERO (CRD42022366309) and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Databases, including PubMed, Embase, CINAHL, Scopus, Web of Science, PEDro, SPORTDiscus and the Cochrane Central Register of Controlled Trials, and the data registry ClinicalTrials.gov were searched from inception to 8 June 2023. Observational studies (cross-sectional and cohort) and interventional studies reporting on the association and prevalence of sarcopenia in MCI, AD or other types of dementia in adults ≥50years were included. For the meta-analysis, pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated for the association of sarcopenia with the neurocognitive disorders using random-effects/fixed-effects models. Subgroup analyses were performed to identify potential sources of heterogeneity. A total of 77 studies consisting of 92058 subjects were finally included in the qualitative analysis (71 cross-sectional, 4 cohort and 2 interventional studies). Studies were heterogeneous, using different diagnostic criteria to define both sarcopenia and cognitive status. The majority of studies (n=38) included Asian community-dwelling older adults. Most studies investigated the association of sarcopenia with AD (33/77) and MCI (32/77). For studies focusing on other forms of dementia, two studies included Lewy body dementia and one study included Parkinson's dementia, whereas the remaining studies did not specify dementia aetiology (n=21). Three cohort studies explored the association between sarcopenia and incident MCI, whereas only one cohort study explored the association between dementia and incident sarcopenia. Two interventional studies investigated whether an exercise programme could prevent the progression of sarcopenia in older adults with dementia or AD. The information for the meta-analysis was extracted from 26 studies. Sarcopenia was significantly associated with MCI (pooled OR=1.58, 95% CI 1.42-1.76) (n=14), AD (pooled OR=2.97, 95% CI 2.15-4.08) (n=3) and non-AD dementia (pooled OR=1.68, 95% CI 1.09-2.58) (n=9). The significance and magnitude of the associations differed in subgroup analyses by study design, population, definition of sarcopenia or used tool to measure cognitive status. This meta-analysis showed that sarcopenia is significantly associated with MCI, AD and other types of dementia. These findings suggest the importance of early screening and prevention of sarcopenia in older people with cognitive dysfunction, although further longitudinal research is needed to clarify the causal relationship.

Association of Rest-Activity Rhythm and Risk of Developing Dementia or Mild Cognitive Impairment in the Middle-Aged and Older Population: Prospective Cohort Study.

The relationship between 24-hour rest-activity rhythms (RARs) and risk for dementia or mild cognitive impairment (MCI) remains an area of growing interest. Previous studies were often limited by small sample sizes, short follow-ups, and older participants. More studies are required to fully explore the link between disrupted RARs and dementia or MCI in middle-aged and older adults. We leveraged the UK Biobank data to examine how RAR disturbances correlate with the risk of developing dementia and MCI in middle-aged and older adults. We analyzed the data of 91,517 UK Biobank participants aged between 43 and 79 years. Wrist actigraphy recordings were used to derive nonparametric RAR metrics, including the activity level of the most active 10-hour period (M10) and its midpoint, the activity level of the least active 5-hour period (L5) and its midpoint, relative amplitude (RA) of the 24-hour cycle [RA=(M10-L5)/(M10+L5)], interdaily stability, and intradaily variability, as well as the amplitude and acrophase of 24-hour rhythms (cosinor analysis). We used Cox proportional hazards models to examine the associations between baseline RAR and subsequent incidence of dementia or MCI, adjusting for demographic characteristics, comorbidities, lifestyle factors, shiftwork status, and genetic risk for Alzheimer's disease. During the follow-up of up to 7.5 years, 555 participants developed MCI or dementia. The dementia or MCI risk increased for those with lower M10 activity (hazard ratio [HR] 1.28, 95% CI 1.14-1.44, per 1-SD decrease), higher L5 activity (HR 1.15, 95% CI 1.10-1.21, per 1-SD increase), lower RA (HR 1.23, 95% CI 1.16-1.29, per 1-SD decrease), lower amplitude (HR 1.32, 95% CI 1.17-1.49, per 1-SD decrease), and higher intradaily variability (HR 1.14, 95% CI 1.05-1.24, per 1-SD increase) as well as advanced L5 midpoint (HR 0.92, 95% CI 0.85-0.99, per 1-SD advance). These associations were similar in people aged <70 and >70 years, and in non-shift workers, and they were independent of genetic and cardiovascular risk factors. No significant associations were observed for M10 midpoint, interdaily stability, or acrophase. Based on findings from a large sample of middle-to-older adults with objective RAR assessment and almost 8-years of follow-up, we suggest that suppressed and fragmented daily activity rhythms precede the onset of dementia or MCI and may serve as risk biomarkers for preclinical dementia in middle-aged and older adults.

Estimating Gender Differences in the Association between Cognitive Resilience and MCI Incidence.

Recent evidence suggests that the influence of verbal intelligence and education on the onset of subjective cognitive decline may be modulated by gender, where education contributes less to cognitive resilience in women than in men. This study aims to examine gender differences in the association between cognitive resilience (CR) and mild cognitive impairment (MCI) incidence in an Australian population-based cohort. We included 1806 participants who had completed at least the first two waves and up to four waves of assessments in the Personality and Total Health (PATH) through life study (Baseline: 49% Female, Mage=62.5, SD=1.5), age range=60-66). CR proxies included measures of educational attainment, occupation skill, verbal intelligence, and leisure activity. Discrete-time survival analyses were conducted to examine gender differences in the association between CR proxies and MCI risk, adjusting for age and Apolipoprotein E4 status. Gender differences were only found in the association between occupation and MCI risk, where lower occupation skill was more strongly associated with higher risk in men than in women (OR = 1.30, 95% CI[1.07, 1.57]). In both genders, after adjusting for education and occupation, one SD increase in leisure activity was associated with lower MCI risk by 24% (OR = 0.76, 95% CI[0.65, 0.89]). Higher scores in verbal intelligence assessment were associated with reduced risk of MCI by 22% (OR = 0.78, 95% CI[0.69, 0.89]). Occupational experience may contribute to cognitive resilience differently between genders. Life-course cognitive engagement and verbal intelligence may be more protective against MCI than education and occupation for both men and women.

Machine Learning-Based Perivascular Space Volumetry in Alzheimer Disease.

Impaired perivascular clearance has been suggested as a contributing factor to the pathogenesis of Alzheimer disease (AD). However, it remains unresolved when the anatomy of the perivascular space (PVS) is altered during AD progression. Therefore, this study investigates the association between PVS volume and AD progression in cognitively unimpaired (CU) individuals, both with and without subjective cognitive decline (SCD), and in those clinically diagnosed with mild cognitive impairment (MCI) or mild AD. A convolutional neural network was trained using manually corrected, filter-based segmentations (n = 1000) to automatically segment the PVS in the centrum semiovale from interpolated, coronal T2-weighted magnetic resonance imaging scans (n = 894). These scans were sourced from the national German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study. Convolutional neural network-based segmentations and those performed by a human rater were compared in terms of segmentation volume, identified PVS clusters, as well as Dice score. The comparison revealed good segmentation quality (Pearson correlation coefficient r = 0.70 with P < 0.0001 for PVS volume, detection rate in cluster analysis = 84.3%, and Dice score = 59.0%). Subsequent multivariate linear regression analysis, adjusted for participants' age, was performed to correlate PVS volume with clinical diagnoses, disease progression, cerebrospinal fluid biomarkers, lifestyle factors, and cognitive function. Cognitive function was assessed using the Mini-Mental State Examination, the Comprehensive Neuropsychological Test Battery, and the Cognitive Subscale of the 13-Item Alzheimer's Disease Assessment Scale. Multivariate analysis, adjusted for age, revealed that participants with AD and MCI, but not those with SCD, had significantly higher PVS volumes compared with CU participants without SCD (P = 0.001 for each group). Furthermore, CU participants who developed incident MCI within 4.5 years after the baseline assessment showed significantly higher PVS volumes at baseline compared with those who did not progress to MCI (P = 0.03). Cognitive function was negatively correlated with PVS volume across all participant groups (P ≤ 0.005 for each). No significant correlation was found between PVS volume and any of the following parameters: cerebrospinal fluid biomarkers, sleep quality, body mass index, nicotine consumption, or alcohol abuse. The very early changes of PVS volume may suggest that alterations in PVS function are involved in the pathophysiology of AD. Overall, the volumetric assessment of centrum semiovale PVS represents a very early imaging biomarker for AD.

Establishment of a mild cognitive impairment risk model in middle-aged and older adults: a longitudinal study.

Early identification individuals at high risk of mild cognitive impairment (MCI) is essential for prevention and intervention strategies of dementia, such as Alzheimer's disease. MCI prediction considering the interdependence of predictors in longitudinal data needs to be further explored. We aimed to employ machine learning (ML) to develop and verify a prediction model of MCI. In a longitudinal population-based cohort of China Health and Retirement Longitudinal Study (CHARLS), 8390 non-MCI participants were enrolled. The diagnosis of MCI was based on the aging-associated cognitive decline (AACD), and 13 factors (gender, education, marital status, residence, diabetes, hypertension, depression, hearing impairment, social isolation, physical activity, drinking status, body mass index and expenditure) were finally selected as predictors. We implemented a long short-term memory (LSTM) to predict the MCI risks in middle-aged and older adults within 7years. The Receiver Operating Characteristic curve (ROC) and calibration curve were used to evaluate the performance of the model. Through 7years of follow-up, 1925 participants developed MCI. The model for all incident MCI achieved an AUC of 0.774, and its deployment to the participants followed 2, 4, and 7years achieved results of 0.739, 0.747, and 0.750, respectively. The model was well-calibrated with predicted probabilities plotted against the observed proportions of cognitive impairment. Education level, gender, marital status, and depression contributed most to the prediction of MCI. This model could be widely applied to medical institutions, even in the community, to identify middle-aged and older adults at high risk of MCI.

Association of glycogen synthase kinase-3β with cognitive impairment in type 2 diabetes patients: a six-year follow-up study.

Our previous multicenter case-control study showed that aging, up-regulation of platelet glycogen synthase kinase-3β (GSK-3β), impaired olfactory function, and ApoE ϵ4 genotype were associated with cognitive decline in type 2 diabetes mellitus (T2DM) patients. However, the causal relationship between these biomarkers and the development of cognitive decline in T2DM patients remains unclear. To further investigate this potential relationship, we designed a 6-year follow-up study in 273 T2DM patients with normal cognitive in our previous study. Baseline characteristics of the study population were compared between T2DM patients with and without incident mild cognitive impairment (MCI). We utilized Cox proportional hazard regression models to assess the risk of cognitive impairment associated with various baseline biomarkers. Receiver operating characteristic curves (ROC) were performed to evaluate the diagnostic accuracy of these biomarkers in predicting cognitive impairment. During a median follow-up time of 6 years (with a range of 4 to 9 years), 40 patients (16.13%) with T2DM developed MCI. Participants who developed incident MCI were more likely to be older, have a lower education level, have more diabetic complications, a higher percentage of ApoE ϵ4 allele and a higher level of platelet GSK-3β activity (rGSK-3β) at baseline (P<0.05). In the longitudinal follow-up, individuals with higher levels of rGSK-3β were more likely to develop incident MCI, with an adjusted hazard ratio (HR) of 1.60 (95% confidence interval [CI] 1.05, 2.46), even after controlling for potential confounders. The AUC of the combination of age, rGSK-3β and ApoEϵ4 allele predicted for incident MCI was 0.71. Platelet GSK-3β activity could be a useful biomarker to predict cognitive decline, suggesting the feasibility of identifying vulnerable population and implementing early prevention for dementia.

Impaired Kidney Function, Cerebral Small Vessel Disease and Cognitive Disorders: The Framingham Heart Study.

It remains unclear if the relation of chronic kidney disease (CKD) with cognitive dysfunction is independent of blood pressure (BP). We evaluated kidney function in relation to premorbid BP measurements, cerebral small vessel disease (CSVD) and incident mild cognitive impairment (MCI) and dementia in Framingham Offspring Cohort participants. We included Framingham Offspring participants free of dementia, attending an examination during midlife (exam cycle 6, baseline) for ascertainment of kidney function status, with brain MRI late in life (exam cycles 7-9), cognitive outcome data and available interim hypertension and blood pressure assessments. We related CKD (estimated glomerular filtration rate<60ml/min/1.73m2) and albuminuria (urine albumin-to-creatinine ratio≥30mg/g) to CSVD markers and cognitive outcomes using multivariable regression analyses. Among 2604 participants (mean age 67.4±9.2, 64% women, 7% had CKD and 9% albuminuria), albuminuria was independently associated with covert infarcts (adjusted OR, 1.55 [1.00-2.38]; P=0.049) and incident MCI and dementia (adjusted HR, 1.68 [1.18-2.41]; P=0.005 and 1.71, [1.11-2.64]; P=0.015, respectively). CKD was not associated with CSVD markers but was associated with higher risk of incident dementia (HR, 1.53 [1.02-2.29]; P=0.041), While albuminuria was predictive of the Alzheimer's disease subtype (Adjusted HR=1.68, [1.03-2.74]; P=0.04), CKD was predictive of vascular dementia (Adjusted HR, 2.78, [1.16-6.68]; P=0.023). Kidney disease was associated with CSVD and cognitive disorders in asymptomatic community dwelling participants. The relation was independent of premorbid BP, suggesting that the link between kidney and brain disease may involve additional mechanisms beyond blood pressure related injury.

Chronic Non-cancer Pain and Associated Risks of Incident Mild Cognitive Impairment and Alzheimer's Disease and Related Dementias in Middle-Aged and Older Adults.

The goal of this study is to investigate the association between chronic non-cancer pain (CNCP) and mild cognitive impairment (MCI)/Alzheimer's disease and related dementias (ADRDs) development among adults aged ≥50 using administrative claims data from a national commercial health insurance company during 2007-2017. To reduce selection bias, propensity-score matching was applied to select comparable CNCP and non-CNCP patients. Time-dependent Cox proportional-hazards regressions were conducted to estimate the hazard ratios (HRs) of incident MCI/ADRDs. Of 170,900 patients with/without CNCP, 0.61% developed MCI and 2.33% had been diagnosed with ADRDs during the follow-up period. Controlling for potential confounders, CNCP patients had a 123% increase in MCI risk (HR = 2.23; 95% CI = 1.92-2.58) and a 44% increase in ADRDs risk (HR = 1.44; 95% CI = 1.34-1.54) relative to non-CNCP patients. CNCP is a risk factor for MCI/ADRDs. Promoting awareness and improving early CNCP diagnosis in middle-aged and older adults should be incorporated into cognitive impairment and dementia prevention.

Predicting the incidence of mild cognitive impairment with a computer-based cognitive assessment tool in community-dwelling older adults: The Otassha study.

This study examined the ability of a computer-based cognitive assessment tool (CompBased-CAT) to predict mild cognitive impairment (MCI) in community-dwelling older adults. A two-year longitudinal study was conducted using data from 2016 to 2018 from the Otassha study cohort of community-dwelling older adults. MCI was defined as a Mini-Mental Status Examination (MMSE) score of <27. The CompBased-CAT was used at baseline, with each subtest score converted into a Z-score. Subsequently, the total Z-scores were calculated. Participants were divided into robust and MCI groups, and all variables were compared using the t-test or χ2 test. Receiver operating characteristic (ROC) curves and logistic regression analyses were conducted, with MCI and total Z-scores as dependent and independent variables, respectively. Among the 455 participants (median age, 72 years; range, 65-89 years; 282 women and 173 men), 32 developed MCI after two years. The participants in the MCI group were significantly older. They had lower maximal gait speed, baseline MMSE scores, subtest Z-scores, and total Z-scores than those in the robust group. The area under the ROC curve was 0.79 (95% confidence interval: 0.70-0.87; P <0.01). The sensitivity was 0.76, and the specificity was 0.75. The logistic regression analysis showed an odds ratio of 1.34 (95% confidence interval: 1.18-1.52; P <0.01). This study showed that CompBased-CAT can detect MCI, which is an early stage of dementia. Thus, CompBased-CAT can be used in future community health checkups and events for older adults.

Clinical characteristics and associated factors of mild cognitive impairment in patients with common cardiovascular diseases

Objective: To analyze the clinical characteristics of patients with common cardiovascular diseases (CVD, including hypertension, coronary heart disease, atrial fibrillation, and heart failure) combined with mild cognitive impairment (MCI) and explore the potential risk factors of MCI in patients with CVD. Methods: A total of 2 294 patients with common cardiovascular diseases who met the criteria at Cardiology Medical Center in Beijing Anzhen Hospital, Capital Medical University, from June 1, 2021, to January 5, 2022, were retrospectively included. The patients were divided into the normal cognitive function group (1 107 cases) and the MCI group (1 187 cases). Demographic information and CVD status were collected. The information of cognitive function were collected using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) scales. The difference between normal cognitive function and MCI were compared and analyzed. The logistic regression analysis was used to explored risk factors of MCI in CVD patients. Results: A total of 2 294 patients aged (60.6±10.4) years were included, among whom there were 29.99% (688 cases) females. Compared with patients in the normal cognitive function group, patients in the MCI group were older [ (57.9±11.4) vs (63.1±8.9) years old, P<0.001], with a higher proportion of women [26.47% (293 cases) vs 33.28% (395 cases), P<0.001]; there was a higher proportion of patients suffering from hypertension in the MCI group [59.62% (660 cases) vs 64.62% (767 cases), P=0.014］, and more components of CVD [(1.68±0.62) vs (1.74±0.65) components, P=0.017]. The risk factors of MCI in patients with common CVD were increased age, increased depression score, combined with hypertension, and ≥3 common components of CVD, with OR (95%CI) of 1.043 (1.032-1.054), 1.021 (1.004-1.037), 1.151 (1.142-3.439), and 1.137 (1.023-1.797), respectively (all P values <0.05). Increasing education level was observed to be associated with reduced risk of MCI with OR (95%CI) of 0.319 (0.271-0.378) (P<0.05). Conclusions: The incidence of MCI was high in CVD patients. The risk factors of MCI in CVD patients included hypertension and≥3 common components of CVD.

Incident dementia risk among patients with type 2 diabetes receiving metformin versus alternative oral glucose-lowering therapy: an observational cohort study using UK primary healthcare records

Introduction4.2 million individuals in the UK have type 2 diabetes, a known risk factor for dementia and mild cognitive impairment (MCI). Diabetes treatment may modify this association, but existing evidence...

Changes in mild cognitive impairment and sociodemographic disparity among adults aged 55 years and above in 4 provinces of China

To investigate the changes in mild cognitive impairment(MCI) and sociodemographic disparity among adults aged 55 years and above in 4 provinces of China. A total of 4687 adults aged 55 years and above from Community-based Cohort Study on Nervous System Disease who did not have Alzheimer&apos;s disease, participated in both rounds of the survey, and had complete baseline sociodemographic data and two rounds of data on cognitive function were selected. Generalized estimation equations were used to analyse the effect of sociodemographic factors on MCI. The detection rates of MCI in adults aged 55 years and above without Alzheimer&apos;s disease in 4 provinces of China in 2018 and 2020 were 48.56% and 42.56% respectively. MCI occurred in 30.11% of those with normal cognition(NC) at baseline, and 44.24% of those with MCI at baseline reverted to NC. The risk of MCI increased and the likelihood of MCI reversion decreased with increasing age and decreasing per capita monthly household income. In the baseline NC population, the risk of MCI in the junior high school and above group was 35% lower than that in the illiterate group(RR=0.65, 95%CI 0.53-0.80), the risk of MCI was lower in those living in rural areas(RR=0.56, 95%CI 0.49-0.65), and the risk of MCI was 1.17 times(95%CI 1.03-1.32) higher in those with a history of chronic diseases than in those without it. In the baseline MCI population, the likelihood of MCI reversion increased with education, the likelihood of MCI reversion was 1.04 times higher for workers than for non-workers(95%CI 1.00-1.08). The incidence and reversal rates of MCI were high in adults aged ≥55 years in four provinces of China. Advanced age, low education and low income level are risk factors for cognitive dysfunction.

The risk of developing dementia in the COVID-19 pandemic; a cohort study.

The effects of the COVID-19 pandemic on cognitive decline are not fully understood. Higher social activity and relationships have been associated with decreased risk of dementia. We hypothesised that risk of transition to dementia would increase after the start of the first national lockdown. We obtained data from the Brains for Dementia (BDR) cohort, which has collected roughly annual data on 3726 older adults with and without dementia since 2008. Data continued to be collected during the lockdowns, although by telephone and/or video call instead of in person. Individuals diagnosed with dementia at study entry were excluded from this study as were individuals with only one visit. Cognitive status was classified using the Clinical Dementia Rating (CDR) global score. Poisson regression with cubic splines to account for differences in age was used to compare the incidence of dementia before and after March 1st 2020. Out of 2242 individuals, 208 individuals developed dementia before and 50 developed dementia after 01/03/20. The incidence rate ratio of developing dementia after 01/03/20 was 0.847 (0.538-1.335) p=0.570. In our secondary analysis we found that the positive association between mild cognitive impairment (MCI) and dementia incidence decreased after 1/3/20 (interaction effect p=0.031). The incidence of dementia as defined using the CDR global score did not change significantly after the first lockdown began, but we found evidence that lockdown decreased the positive association between MCI and dementia incidence. This may reflect that individuals were progressing to dementia more rapidly and thus missing the MCI stage or that assessing patients over the phone made diagnosing MCI more challenging.

THE TYPES AND CONSISTENCY OF PARTICIPANT-SPECIFIED PROXIES DURING THE SPRINT CLINICAL TRIAL

Abstract Background For clinical trials or patient care, reports from a person familiar with the trajectory of a participant’s cognition are needed to ascertain incident Mild Cognitive Impairment and dementia. Informants offer a more unbiased evaluation of cognitive status. Recent large clinical trials studies, such as SPRINT, provide information about the contributions and consistency of informants throughout extended follow-up. Methods SPRINT participants named proxies and relationship at study onset. Proxies provided information for the Functional Activities Questionnaire (FAQ) and Dementia Questionnaire (DQ). We collapsed proxy relationships into seven categories and evaluated the proportion of proxies in each category at baseline, how frequently the same proxy was retained to the last visit, and the frequency of successful proxy contact during the trial. Results Of the 9,361 randomized SPRINT participants, 7,586 participants listed a proxy relationship from which we identified 7 categories. Participants were 35.6% female, with baseline mean age of 67.9 years. The proportion of proxies in each category was spouse/partner (51.7%), child (23.6%), sibling (8.7%), other family member (6.2%), and unelated (8.8%). The overall consistency of proxy continuation between the baseline and final SPRINT visit (mean 5.1 years) was 90.11%. Proxy consistency from first visit to last visit for a child was 93.41%, spouse/partner (91.87%), other family member (80.1%), brother/sister (86.2%), non-related (84.65%), and parent (81.73%). Conclusion Immediate family members (spouse, child, or sibling) comprised the majority of proxies in SPRINT. Importantly, more than 90% of identified proxies at baseline continued to be available over the life of a 5-year trial.

The relationship between perceived stigma and perceived stress in cognitive decline: a survey of persons with mild cognitive impairment and their caregivers.

While Alzheimer's disease and other causes of dementia have rapidly become a global health crisis with growing incidence that is unabated, the incidence of Mild Cognitive Impairment (MCI) far exceeds that of Alzheimer's disease. Persons with MCI demonstrate some level of cognitive impairment, but daily functions remain intact and there is no certainty that they will develop dementia. Yet, the possibility conjures a considerable amount of fear and anxiety, further fueled by a vast array of misconceptions and stigma. The pervasive nature of this stigma permeates society and culture at many levels. Persons with MCI who are at higher risk for development of dementia may be especially vulnerable to fear and stigma associated with the diagnosis. Based on this premise, the primary aim of this study was to examine the relationship between perceived stigma and perceived stress in persons with MCI and their care partners, including the relationship between income and the study variables. The secondary aim was to examine the effect of a combined cognitive rehabilitation and wellness program on these perceptions. Thirty participants were recruited from Mayo Clinic's Health Action to Benefit Independence and Thinking (HABIT) program. MCI (n = 15) and care partner (n = 15) participants completed the Stigma Impact Scale (SIS) and the Perceived Stress Scale (PSS) before and after the HABIT program. Average SIS and PSS scores decreased in the MCI, care partner, and combined groups, both pre- and post-HABIT. Linear regression was used to assess the relationship between perceived stigma and stress, controlling for income. A significant relationship was found between perceived stigma and perceived stress both pre and post-HABIT. The results suggest a relationship exists between perceived stigma and perceived stress in persons with MCI and their care partners, and an educational program such as HABIT may strengthen this relationship by informing participants of potential challenges that occur in cognitive decline. Understanding these relationships may provide an opportunity to provide tools for this vulnerable population.

Incidence of Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) in the United States Medicare population

AbstractBackgroundAlzheimer’s disease (AD) is a chronic, neurodegenerative condition. Mild cognitive impairment (MCI) is characterized by cognitive decline, without dementia. We aimed to estimate the incidence of AD and MCI among Medicare beneficiaries.MethodPatients were identified from the US Center for Medicare and Medicaid Services (CMS) database using International Classification of Diseases (ICD) codes for AD (331.0, G30.9, G30.8, or G30.1,) and MCI (331.83 or G31.84). Both AD and MCI were identified using the search rule of 2 ICD codes ≥30 days apart ≤365 days from both Medicare fee‐for‐service (FFS: 2008‐2018) and Medicare Advantage (MA: 2015‐2018). US regions were derived using zip codes and categorized by National Center for Chronic Disease Prevention/Health Promotion regions. Yearly incidence was defined as the number of new cases of AD or MCI in each year divided by the population at risk in the year. Confidence intervals were not reported due to small intervals.ResultThe incidence of AD and MCI per 10,000 person‐years was 82.9 and 4.9, 80.3 and 7.4, 74.5 and 9.3, 69.8 and 10.9, 65.3 and 13.4, 62.8 and 15.8, 60.7 and 17.4, 65.5 and 20.7, 61.4 and 22.4, 56.0 and 22.9, and 52.2 and 23.2 spanning from 2008 through 2018, respectively. In 2018, the incidence of AD and MCI per 10,000 person‐years by demographic subgroups was: 43 and 21 for men and 59 and 25 for women; 16 and 10 among those aged 65‐69 years, 30 and 18 for ages 70‐74 years, 58 and 30 for ages 75‐79, 102 and 44 for ages 80‐84, 176 and 57 for age ≥85 years old; 56 and 26 for Whites, 38 and 13 for Blacks, and 43 and 15 for Asians. The incidence of AD and MCI per 10,000 person‐years in 2018 was highest in the US Northeast, especially in New Hampshire (77 and 39), Vermont (74 and 47), and New Jersey (73 and 33).ConclusionAmong Medicare beneficiaries from 2008 to 2018, AD incidence generally decreased while MCI increased. Women, older age, White race, and Northeast region were associated with higher incidence of AD and MCI in 2018.

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&lt;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&lt;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.

Longitudinal change of plasma biomarkers with incident mild cognitive impairment or Alzheimer’s disease in a multi‐ethnic cohort

AbstractBackgroundThe utility of plasma‐based Alzheimer’s biomarkers in differentiating cognitively healthy individuals from those with Mild Cognitive Impairment (MCI) or Alzheimer’s disease (AD) has been widely investigated in cross‐sectional studies. There are fewer data on longitudinal change of these biomarkers over time, particularly in multi‐ethnic cohorts.MethodBased on a community‐based, multi‐ethnic cohort study, the Washington Heights Inwood Columbia Aging Project, we included 610 cognitively normal individuals with three plasma samples collected over a mean period of 6.7 years. We used AD biomarkers, including Aβ40, Aβ42, tau, phosphorylated tau‐181 (P‐tau181), glial fibrillary acid protein (GFAP), and neurofilament light chain (NfL), and two calculated ratio measures (Aβ42/Aβ40, P‐tau181/Aβ42). During the follow‐up, 156 individuals developed MCI, 50 developed AD, and 404 remained cognitively unimpaired. We used generalized estimating equations to examine whether those who developed MCI and AD had different rates of change in plasma biomarkers than controls. Analyses were adjusted for age, years of education, sex, race and ethnicity, and APOE ɛ4 status. Similar analyses were performed to examine whether the rate of biomarker change differed by race and ethnicity, sex, and APOE ɛ4 status.ResultThe initial mean age of individuals was 73.1 (SD = 5.6) years, 419 (69%) were women, and 25.9% carried APOE e4. Individuals self‐identified as non‐Hispanic White (28.9%), non‐Hispanic Black (25.4%), or Hispanic (45.7%). Compared to controls, individuals with incident MCI had an accelerated increase in P‐tau181 (b = 0.029, p = 0.048), NfL (b = 0.027, p = 0.010), GFAP (b = 0.029, p = 0.002), and a more rapid decrease in Aβ42/Aβ40 ratio (b = ‐0.015, p = 0.033). Individuals with incident AD also had a greater increase in NfL (b = 0.041, p = 0.027) and GFAP (b = 0.04, p = 0.006) than controls. Hispanics had a faster increase in NfL (b = 0.033, p = 0.002) and GFAP (b = 0.034, p&lt;0.001), and Black participants had a faster increase in NfL (b = 0.028, p = 0.023), compared to Whites. Neither sex nor APOE ɛ4 genotype affected rates of biomarker changes.ConclusionLongitudinal change in plasma biomarkers may have clinical utility, since incident MCI and AD are accompanied by faster increases in P‐tau181, NfL, and GFAP, and a faster decrease in Aβ42/ Aβ40 ratio. The trajectories of AD biomarker change may also vary by race and ethnicity.

Impact of type, intensity, frequency, duration and volume of physical activity on dementia and mild cognitive impairment in older adults: protocol for a systematic review and meta-analysis

IntroductionWorldwide, the prevalence of degenerative diseases such as dementia and mild cognitive impairment (MCI) is increasing with population ageing and increasing life expectancy. Both conditions share modifiable risk factors. Physical...