Slow Cognitive Decline Research Articles

Direct Effect of Life-Course Socioeconomic Status on Late-Life Cognition and Cognitive Decline in the Rush Memory and Aging Project.

The role of socioeconomic status (SES) across the life course in late-life cognition is unclear. We tested the hypotheses that: 1) High SES in childhood, young adulthood, midlife, and late life have independent causal effects on higher cognition level and slower cognitive decline; 2) Compared with stable low SES (referent), stable high SES has the largest estimated effect for higher cognition level and slower decline among life-course SES combinations. The Rush Memory and Aging Project enrolled 1,940 dementia-free older adults in northeastern Illinois (1997-2018). We used inverse probability-weighted marginal structural models to estimate the joint and independent effect of each life-course SES on global and domain-specific cognition. A total of 1,746 participants had, on average, 6 years of follow-up. High SES at each life-course stage starting in young adulthood had a protective estimated effect on global and domain-specific cognition intercepts. Compared with consistently low SES, consistently high SES (β= 0.64, 95% confidence interval: 0.48, 0.93) and high SES beyond childhood (β= 0.64, 95% confidence interval: 0.47, 0.83) had the largest benefit for global cognition intercepts. None of the life-course SES measures influenced rate of global or domain-specific decline. Additional understanding of life-course SES components influencing cognitive level is warranted.

Protein-Balanced Dietary Habits Benefit Cognitive Function in Japanese Older Adults.

Since daily dietary habits can affect cognitive function, dietary patterns such as the Mediterranean-DASH Intervention for Neurodegenerative Delay diet have been proposed as interventions to slow cognitive decline. However, because dietary habits vary widely among different food cultures, it is necessary to establish dietary pattern intervention methods that are appropriate for each population. Therefore, in this study, the dietary patterns of elderly Japanese individuals were classified using cluster analysis, and their relationship with cognitive function was investigated. We then modeled the dietary patterns and applied them to another cohort of elderly Japanese individuals to determine whether differences in dietary patterns could predict cognitive decline. One hundred and fifty older adults ≥ 65 years of age in the community were recruited. Their daily food intake and cognitive function were measured using the brief-type self-administered diet history questionnaire and Montreal Cognitive Assessment, respectively. K-means cluster analysis identified a high-carbohydrate (HC) dietary pattern with high cereal intake and a protein-balanced (PB) dietary pattern with high intake of legumes, vegetables, seafood, meat, and eggs. Cognitive function was significantly higher in the PB group than in the HC group. Furthermore, to classify the new data into HC and PB patterns, a classification model was created by discriminant analysis using food groups with significantly different intakes among dietary patterns. Next, we recruited 267 new older adults ≥ 65 years of age and measured food intake and cognitive function assessed using the memory performance index score. Individuals with cognitive decline were identified and their detailed cognitive functions were assessed using the neurocognitive index score. Cognitive function was significantly impaired in the HC pattern in both the general elderly and cognitively impaired cohorts. These findings suggest that a dietary pattern of low carbohydrate and high protein intake is associated with good cognitive function in elderly Japanese individuals. Classification by these dietary patterns can predict cognitive reservation in community-dwelling older adults.

Social Health and Cognitive Change in Old Age: Role of Brain Reserve.

Individual aspects of social health (SH; eg, network, engagement, support) have been linked to cognitive health. However, their combined effect and the role of the structural properties of the brain (brain reserve [BR]) remain unclear. We investigated the interplay of SH and BR on cognitive change in older adults. Within the Swedish National Study on Aging and Care-Kungsholmen, 368 dementia-free adults aged ≥60 years with baseline brain magnetic resonance imaging were followed over 12 years to assess cognitive change. A measure of global cognition was computed at each of the 5 waves of assessment by averaging domain-specific Z scores for episodic memory, perceptual speed, semantic memory, and letter and category fluency. An SH composite score was computed at baseline by combining leisure activities and social network. BR was proxied by total brain tissue volume (TBTV). Linear mixed models (adjusted for sociodemographic, vascular, and genetic factors) were used to estimate cognitive trajectories in relation to SH and TBTV. Interaction analysis and stratification were used to examine the interplay between SH and TBTV. Moderate-good SH (n=245; vs poor, β-slope=0.01, 95% confidence interval [CI] = 0.002-0.02, p= 0.018) and moderate-to-large TBTV (n=245; vs small, β-slope=0.03, 95% CI=0.02-0.04, p< 0.001) were separately associated with slower cognitive decline. In stratified analysis, moderate-good SH was associated with higher cognitive levels (but not change) only in participants with moderate-to-large TBTV (β-intercept=0.21, 95% CI=0.06-0.37, p< 0.01; interaction SH * TBTV, p< 0.05). Our findings highlight the interplay between SH and BR that likely unfolds throughout the entire life course to shape old-age cognitive outcomes. ANN NEUROL 2023;93:844-855.

Physical Activity Is Associated with Slower Cognitive Decline in Older Adults with Type 2 Diabetes.

Physical activity is associated with slower cognitive decline in old age. Type 2 diabetes (T2d) is a risk factor for dementia and cognitive decline. Physical activity protects against several T2d complications. Yet, little is known about the contribution of physical activity to cognitive health among the elderly with T2d. To examine the association between physical activity and cognitive decline in older adults with T2d. This is a prospective longitudinal study using data from the Israel Diabetes and Cognitive Decline (IDCD) study. ICDC study (N=1,213), is a population-based cohort of adults over the age of 65, diagnosed with type 2 diabetes, who were cognitively normal at baseline and followed up every 18 months. Participants with at least one follow-up assessment who were in the same physical activity group consistently and had complete demographic data. Physical activity was measured using Minnesota Leisure Time Activity Questionnaire, cognitive functioning was measured using a broad neuropsychological assessment measuring Executive Functioning, Attention/Working Memory, Semantic Categorization and Episodic Memory. Participants were classified into physical activity groups based on self-reported physical activity at baseline and all follow ups: "active" - participation in recreational physical activity (n=286); "non-active"- the only physical activity was walking from place to place (n=93) and "sedentary" (n=19). Linear mixed effects models were applied to adjust for key demographic and cardiovascular risk factors. Participants were 72.4 (SD 4.6) years old, had 13.3 (SD 3.6) years of education, and 163 (41%) were female. In the fully adjusted model, compared to the non-active group the active group had significantly slower rate of decline in Global Cognition (p=0.005), Executive Functioning (p=.014), and Attention/Working Memory (p=.01). There were no significant group differences for Semantic Categorization (p=.17) and Episodic Memory (p=.88). Among initially cognitively normal and independent older adults with T2d, a physically active lifestyle was associated with a slower rate of cognitive decline. Future research should examine whether promoting physical activity may prevent or delay onset of dementia in this high-risk population.

ASSOCIATIONS BETWEEN CUMULATIVE STRESS AND COGNITIVE FUNCTION IN HRS AND ELSA

Abstract Despite growing research linking stressors with poorer cognition, less research explicitly considers stress from several sources, which often co-occurs and accumulate to influence health. We used the Global Gateway Harmonized data (HRS: n=8,888; mean age: 74 years; ELSA: n=6,715; mean age: 65 years) to examine whether higher cumulative stress is associated with lower levels of and faster decline in cognitive function. We fit linear mixed effect models to assess the stress-cognition associations. After adjusting for all covariates, baseline cumulative stress was associated with lower baseline cognitive function in both HRS (β=-0.02, 95%CI -0.04, -0.01) and ELSA (β=-0.03, 95%CI -0.05, -0.01). Unexpectedly, higher baseline cumulative stress was associated with slower cognitive decline in HRS (βtime*stress=0.001, 95%CI 0.002,0.01) but not in ELSA. The stress-cognition associations may differ among adults in the US and the UK. Future research should investigate how cumulative stress may operate differently to influence cognitive function across different populations.

VISION IMPAIRMENT IN A GLOBAL LIFE COURSE MODEL OF POTENTIALLY MODIFIABLE DEMENTIA RISK FACTORS

Abstract Vision impairment (VI) is a risk factor for accelerated cognitive decline and incident dementia. An estimated 90% of VI is preventable. Nonetheless, VI has not been included in the dominant life-course models of dementia risk factors. We sought to strengthen existing models of potentially modifiable dementia risk factors through the inclusion of VI using cross-sectional survey data from the Gateway to Global Aging project (G2Aging) from 31 countries. Prevalence rates and communalities from the G2Aging will be used to estimate the population attributable fraction (PAF) of dementia due to VI. It is expected that the PAF for VI will range from 1.0%-2.0%, suggesting that &amp;gt;10,000,000 prevalent dementia cases globally may potentially have been prevented through healthy vision. Since a large majority of VI can be treated with cost-effective but underutilized interventions, this may represent a viable target for future interventional research that aims to slow cognitive decline and prevent dementia.

The Unverricht-Lundborg disease as a part of the progressive myoclonic epilepsies syndrome

The progressive myoclonic epilepsies syndrome (PME) is a heterogeneous group of genetic disorders characterized by myoclonus, progressive motor and cognitive abnormalities, sensory and cerebellar symptoms, abnormal slowing of the basic bioelectrical activity at electroencephalography, and normal cognitive functions and normal development of the patient before manifestation of the disease. Generalized spike-wave complexes at electroencephalography have been also described as an obligatory symptom. The Unverricht-Lundborg disease is a distinct entity within the group with specific age at manifestation (7 to 13 years), as well as slow cognitive and motor decline with stabilization in the adult age. In 90% of the cases, the diagnosis is confirmed by identification of the expanded nucleotide duplicates in the CSTB gene. An adequately tailored anticonvulsant treatment can stabilize and improve the patient's condition. The anticonvulsant therapy should not include sodium channel blockers. Valproate sodium is considered to be the main agent; it is usually combined with levetiracetam/zonisamide/topiramate/benzodiazepins. In the recent years, perampanel has been also used as a part of the combination treatment.

The roller-coaster ride continued for Alzheimer’s drug candidates

A tumultuous sequence of events in 2021 and 2022 surrounded Biogen and Eisai’s Alzheimer’s drug aducanumab. But in September, the companies reported positive clinical trial results for lecanemab, a second amyloid-eliminating monoclonal antibody. In spite of the clinical failure of yet another anti-amyloid drug from Roche 2 months later, experts hail 2022 as an exciting year for Alzheimer’s treatment. During lecanemab’s Phase 3 trial, the compound slowed cognitive decline by 27% among participants with early Alzheimer’s symptoms. The drug candidate is currently under priority review by the US Food and Drug Administration, with a decision slated for Jan. 6. The positive results were a counterpoint to developments with aducanumab. Late last year it became the first anti-amyloid therapy to receive approval from the FDA, but the decision was controversial because the drug had conflicting clinical outcomes during two Phase 3 trials. Aducanumab was a commercial failure , generating low sales

Different associations of varying types of Vitamin E and cognitive function in older adults with or without APOE Ɛ4 allele

AbstractBackgroundDifferent forms of vitamin E may have a different association with cognitive function, which might vary by the APOE E4 allele status. We aim to examine vitamin E from different sources and in varying forms and their relation to cognitive decline among those with and without the APOE E4 allele.MethodsWe included 2,014 participants from the Chicago Health and Aging Project (62% African Americans, 63% female). Global cognition was assessed using a composite score of episodic memory, perceptual speed, and the MMSE. Diet was assessed by a 139‐item FFQ. APOE genotype was assessed by hME Sequenom mass‐array platform. Mixed models were adjusted for age, sex, education, smoking status, calorie intake, alcohol consumption, use of supplements, time since baseline, and the interaction term of time with each covariate.ResultsA higher dietary vitamin E was associated with slower cognitive decline. Those in the highest quintile of dietary vitamin E intake had 28% slower cognitive decline than the lowest quintile (β = 0.014, p = 0.02). A higher intake of dietary αlpha‐tocopherol was associated with slower cognitive decline in participants with APOE E4 allele, but not among those without. In participants with APOE E4 allele and in the highest quintile of alpha‐tocopherol intake had a 16.4% slower rate of global cognitive decline than those in the lowest quintile (β = 0.015, p = 0.0015). A higher intake of delta‐tocopherol was associated with a slower decline in individuals without the APOE E4 allele only. Among those without the APOE E4 allele and in the highest quintile, the rate of global cognitive decline was slower by 22% than the lowest quintile (β = 0.012, p = 0.0014). We found no significant associations between beta‐ and gamma‐tocopherol intakes and cognitive decline among those with and without the APOE E4 allele.ConclusionOur study found a positive association of alpha‐tocopherol with cognitive decline among those with the APOE E4 allele and delta‐tocopherol with the decline in those without the APOE E4 allele. Our findings suggest that different forms of vitamin E might have a different association with cognitive decline in older adults depending on their APOE E4 allele status.

The impact of social health on global cognition and cognitive domains: An individual participant level data meta‐analysis of longitudinal cohort studies of cognitive ageing

AbstractBackgroundThe Social Health and Reserve in the Dementia patient journey (SHARED) project is an international collaboration investigating the association between social health and cognitive function. We conducted an individual participant‐level meta‐analysis of the associations between social health variables and cognitive function (global cognition, memory, language, and executive function).MethodWe obtained individual participant level data (N = 38,641, mean age = 70.5 years, 58.49% female) from 13 longitudinal cohort studies of ageing (12 studies from the COSMIC consortium and the English Longitudinal Study of Ageing). Linear mixed models examined the impact of social health factors, namely relationship status, cohabitation, interactions with friends/family, community group engagement, perceived social support, loneliness, and having a confidante, on global cognition and cognitive domains (memory, language, and executive function).ResultAfter controlling for age, sex, and education, we found significant associations between social health variables and slower cognitive decline over time (Mean follow up = 4.99 years, SD = 3.71 years). Compared to being single, being in a relationship was associated with slower decline in global cognition (b = 0.0132, 95% CI: 0.0044, 0.0220), and language (b = 0.0180, 95CI%: 0.0015, 0.0346). Living with others was associated with slower decline in global cognition (b = 0.0089, 95% CI: 0.0039, 0.0139), and memory (b = 0.0155, 95%CI: 0.0031, 0.0279). Compared to never interacting with friends/family, weekly interactions were associated with slower decline in global cognition (b = 0.0178, 95% CI: 0.0021, 0.0335) and memory (b = 0.0198, 95% CI: 0.0094, 0.0302). Other social variables (community group engagement, loneliness and having a confidante) were not associated with cognitive decline.ConclusionGood social health (specifically, being in a relationship, living with others, and interactions with friends/family) was associated with slower cognitive decline. Further research is required to investigate the causal pathways from social health to cognitive health.

Neuropsychological effects of a six‐month online cognitive health program with a weekly telehealth lifestyle support group and personalized precision medicine recommendations for health optimization in older adults with subjective cognitive impairment

AbstractBackgroundMaintaining healthy lifestyle behaviors and optimizing health may slow cognitive decline through risk reduction in older adults with cognitive impairments. Curriculum‐based health coaching, weekly psychosocial support, and use of biomarkers to guide health optimization may aid in establishing effective behavior change centered around multiple reversible dementia risk factors.MethodWe piloted combined use of a six‐month online Cognitive Health Program (www.amosinstitute.com) with a telehealth lifestyle support group in six patients with subjective cognitive complaints receiving ongoing outpatient memory care. These patients were given lab‐guided personalized health recommendations for dementia risk reduction throughout the pilot intervention during monthly individual appointments with the study physician overseeing the group. A registered dietician was invited to lead the weekly telehealth lifestyle support group, which was delivered in partnership with the Center’s memory clinicians and health coaches. Highlights of the online Cognitive Health Program were reviewed by the dietician each week followed by group discussion on topics including diet, exercise, sleep, stress, and cognitive training. Cognition was assessed at baseline and post‐intervention using a computerized battery (www.cambridgebrainsciences.com). The significance of cognitive changes was estimated with nonparametric tests and effect sizes (Cohen’s d). The participants were also queried qualitatively on adherence and satisfaction.ResultCompared to baseline, the participants improved significantly in the global cognition score (p&lt;.02, d = 1.6), and had significant improvements in spatial planning (p&lt;.01, d = 2.3) and visuospatial processing (p&lt;.05, d = 1.1). There was a borderline improvement in verbal reasoning (p&lt;.06, d = 1.0). Subjective reports indicated that participants were able to successfully adhere to multiple lifestyle habits in the areas of sleep, nutrition, and exercise. Participants reported high levels of satisfaction with the virtual group format, the online curriculum, and access to the additional online resources.ConclusionA virtually administered, six‐month, weekly health coaching group that addresses multiple lifestyle factors associated with brain health, supplemented by self‐paced online health education and lab‐based health optimization by a physician, is feasible and potentially efficacious for improving cognition in participants with subjective cognitive impairment. This format may facilitate behavior change to slow cognitive decline. Future studies will include neuroimaging, formal neuropsychological testing, controls, and larger sample sizes.

PROPOSING THE NEUROGENESIS HYPOTHESIS FOR ALZHEIMER’S DISEASEWITH A CASE STUDY‐ PHASE 2 CLINICAL TRIALS OF NA‐831

AbstractBackgroundIn the hippocampus, new neurons are generated throughout life via a process called adult hippocampal neurogenesis (AHN). In mild cognitive impairment (MCI) and mild to moderate AD (early AD), AHN is reduced suggesting that AHN impairment compromises hippocampal functions. Augmenting AHN could help prevent or slow cognitive decline in MCI and early AD. The neurogenesis hypothesis is supported by the results of a Phase 2 randomized, double‐blind, placebo controlled clinical trial of NA‐831.MethodNA‐831 is a small drug molecule, which activates synaptic AMPA receptors, and increases the expression of brain derived neurotrophic factor (BDNF), which is crucial in synaptic plasticity, learning and memory formation in the hippocampus. NA‐831 restores neurogenesis by increasing the number of DCX+PCNA+ neuroblast cells. The study was conducted in 56 patients with MCI, mild and moderate Alzheimer’s disease, who received 10mg to 30 mg of NA‐831 or placebo orally per day for 24 weeks.ResultNA‐831 provided a significant delay in cognitive decline in MCI as measured by ADAS‐Cog‐13, an average score difference of 3.4 compared to placebo (p = 0.01; ITT) after 24 weeks of treatment. Similarly, NA‐831 delayed cognitive decline in early AD, an average score difference of 4.1 com‐pared to placebo (p = 0.001; ITT). CIBIC‐Plus showed 78% of the study participants receiving NA‐831 improved (p = 0.01; ITT). NA‐831 was well‐tolerated at 30 mg/day for 24 weeks, and no serious adverse events were observed.ConclusionThe Neurogenesis Hypothesis, and details of the Phase 2 clinical trials will be presented and discussed.

Resilience and Reserve mechanisms underlying clinical‐cognitive progression in Dominant Inherited Alzheimer’s Disease.

AbstractBackgroundPrevention of Alzheimer’s dementia may encompass both avoiding the AD pathological processes (resistance) and coping with AD pathology (resilience). Increasing evidence implicates resistance/resilience factors (e.g., level of education, socio‐economic status [SES], physical activity [PA]) occurring through life as potential modifiers of age at symptom onset (AAO) and rate of cognitive decline to dementia. The extent to which life course factors may influence disease progression in Dominantly Inherited Alzheimer’s Disease (DIAD) remains unknown.MethodsWe aimed to examine the influence of life‐course factors on clinical‐cognitive decline and MRI hippocampal volume in individuals with DIAD enrolled in the Dominantly Inherited Alzheimer Network. A total of 310 mutations carriers (195 asymptomatic and 111 symptomatic [CDR&gt;0]) self‐reported education, work complexity, SES, and PA at baseline and completed longitudinal clinical‐cognitive measures, CSF biomarker studies (Aβ‐42, p‐tau‐181, t‐tau), structural MRI and Aβ‐PET imaging. The influence of life‐course risk factors on AAO, cognitive performances, and hippocampal volume were analyzed using linear mixed models.ResultIn mutation carriers (MC), adjusting for age, PiB‐PET SUVR, and sex, lower clinical disease severity as measured by CDR‐SB was associated with higher levels of education (p = 0.04), PA (p = 0.01) and SES (0.002). Similarly, MC with higher educational levels (p = 0.02) and SES levels (p = 0.001) exhibited larger hippocampal volume despite no differences in PiB‐PET SUVR. Longitudinally, MC with higher levels of education, PA, and SES showed better performance and slower cognitive decline in memory and executive function prior to symptom onset (CDR&gt;0), but a similar decline rate after symptom onset.ConclusionLife‐course factors, like higher education, PA, and SES may promote brain resistance and clinical resilience to AD pathology in DIAD. A model of cognitive reserve in DIAD may help to identify how social and behavioral factors influence the progression of AD pathophysiology and explain how a variety of factors may enhance resistance to pathology, delay AAO, and cognitive decline rate.

Racial Differences in the Association of MIND Diet/Physical Activity Combinations and Cognition in older adults

AbstractBackgroundDiet and physical activity (PA) are important factors associated with improved cognition. Few studies have investigated the synergistic association with cognitive decline and further, whether the association differs by race. In this study, we investigate whether the observed association of high MIND diet score/high self‐reported PA and cognitive decline is different between African Americans (AA’s) and European Americans (EA’s).MethodWe examined the association of baseline MIND diet and PA combinations on cognition in 3,657 participants (2206 AAs and 1451 EAs; mean age = 73.2±SD5.8 years) from the Chicago Health and Aging Project. Diet was assessed using a validated 144‐item food frequency questionnaire; self‐reported PA was measured by frequency of engagement in six activities. Cognition was evaluated using a four‐test cognitive battery from which a global composite score and two domains were derived. Participants were followed on average 8.5±SD4.8 years and separated into 9 combinations of MIND diet score and PA (high, moderate, low for MIND diet and high, moderate, low, for PA). Using linear mixed models we examined the rate of cognitive decline; adjusting for age, sex, education, race, ApoE‐4, smoking, and caloric intake. Subsequent models were stratified by race to investigate potential differences in the association of diet and PA combinations with cognitive decline.ResultParticipants who reported high MIND/high PA had a slower rate of decline in global cognition (β = 0.015, 24.87% slower, p = 0.007), memory score (β = 0.014, 31.86% slower, p = 0.042) and improved MMSE (β = 0.023, 33.62% improvement, p&lt;0.001) when compared to participants with low MIND/low PA. In race stratified models, we found that in European Americans, high MIND/high PA was associated with slower rates of decline in global cognition (β = 0.028, 37.1% slower, p = 0.007), memory score (β = 0.026, 48.59% slower, p = 0.033) and improved MMSE (β = 0.050, 50.0% improvement, p&lt;0.0001) versus low MIND diet/low PA. However, only an improved MMSE (β = 0.017, 27.11% improvement, p = 0.033) was observed to be associated in African Americans.ConclusionHigh adherence to MIND diet/physical activity is associated with slower cognitive decline, regardless of race. However, the breadth of these associations may differ by race. Additional studies are required to elucidate the potential racial differences observed and determine which interventions are most impactful.

MIND diet associated with less hippocampal sclerosis: A Community‐Based Neuropathologic Study

AbstractBackgroundMediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet is associated with slower cognitive decline, reduced Alzheimer’s dementia risk, and greater brain volume. We have also shown MIND diet is associated with less Alzheimer’s disease (AD) pathology. Hippocampal sclerosis (HS, severe neuronal loss and astrogliosis in CA1/subiculum), is increasingly recognized as an important pathologic finding associated with TDP‐43 (“LATE‐NC), AD pathology, and dementia. The pathogenesis of HS is not clear but may be neurodegenerative and/or vascular. This study investigates the association of the MIND diet with hippocampal sclerosis in autopsied brains from a community sample.MethodsThe study was conducted among 581 deceased participants (age at death = 91.3 ± 6.1 years; 72% female, education = 14.8 ± 2.8 years) of the Rush Memory and Aging Project. The coronal section of the mid hippocampus CA1 and subiculum were assessed for severe neuronal loss and gliosis to define HS. Mean MIND diet scores were obtained from a validated food frequency questionnaire administered annually during follow‐up years prior to death. We used logistic models adjusted for age at death, sex, education, and total calories to examine associations of MIND diet (continuous and grouped in tertiles) with HS. Further models controlled for APOE‐ε4 status, and other pathologies including global AD pathology, arteriolosclerosis, and LATE‐NC stage.ResultsHigh and moderate adherence to MIND diet was associated with 69% (OR (95% CI) = 0.31(0.15, 0.64)) and 54% (OR (95% CI) = 0.46 (0.24, 0.79)) lower odds of HS. After adjusting for APOE‐ε4 status and AD pathology, the association was retained (T3 vs. T1: OR (95% CI) = 0.30 (0.15, 0.62); T2 vs. T1: (95% CI) = 0.46 (0.24, 0.87); p for trend = 0.0007). Further adjusting for arteriolosclerosis and LATE‐NC did not appreciably change the effect estimates.ConclusionThe MIND diet is associated with a lower likelihood of hippocampal sclerosis. Further studies are needed to more fully understand the role of diet on hippocampal structure and function in the context of AD and related brain pathologies.

Case of Dementia with Lewy Bodies in Young Patient with Family History

AbstractBackgroundDementia with Lewy bodies (DLB) is a neurodegenerative disorder characterized by cognitive decline, fluctuating attention, visual hallucinations, and sleep disorders, sometimes with signs of parkinsonism. Pathological evaluation reveals deposition of abnormally metabolized alpha‐synuclein, termed Lewy bodies. Clinical signs of DLB may be misdiagnosed in young patients with coexisting psychiatric disorders. A 43‐year‐old left‐handed man with a history of chronic paranoid schizophrenia, controlled with haloperidol, paroxetine, quetiapine, and clonazepam, presented with a 3‐year history of declining short‐term memory and concentration. He had a twin brother who was diagnosed with DLB and passed away at 40 years of age.MethodsThe patient was evaluated with serum laboratory tests to evaluate for metabolic abnormalities, infection, and heavy metal toxicity, including complete blood count, comprehensive metabolic panel, vitamin B12, folate, thyroid stimulating hormone, copper, and zinc. MRI Brain and subsequent PET‐FDG Brain were also conducted.ResultsThe results of the serum laboratory tests were all normal. MRI Brain was notable for bilateral parieto‐occipital atrophy and minimal chronic microvascular changes. PET‐FDG Brain revealed hypometabolism in bilateral parietal and occipital regions, with a cingulate island sign, indicative of advanced dementia with Lewy bodies.ConclusionDementia with Lewy bodies is a form of dementia that can sometimes present at an early age, and can be associated with psychological comorbidities and genetic risk factors. Further study of this case will include screening for mutations in the GBA gene, which encodes the enzyme beta‐glucocerebrosidease, which is the most frequent genetic association with dementia with Lewy bodies. Counseling on diagnosis and prognosis has been provided to the patient and his family, and he is being managed with rivastigmine 1.5mg twice daily to help slow down cognitive decline.

Scaling Comprehensive Dementia Care.

Despite scientific progress over the last 25 years, dementia remains one of the toughest health-care challenges. Alzheimer's disease is the sixth-leading cause of death in the United States, and the number of deaths from all related dementias may be twice as high.[i] Years of investment and research in Alzheimer's disease and related dementias (ADRD) are sowing seeds of hope. New treatments aim to slow cognitive decline and manage symptoms. However, because of the complexity of dementia, people living with dementia will likely need a combination of therapeutic treatments, coordinated care, and supportive services to help them live their lives to the fullest post-diagnosis. The Milken Institute Alliance to Improve Dementia Care convened a roundtable in June 2021. Leaders across industry, government, research, advocacy, philanthropy, health systems, and community-based organizations explored ways to improve and pay for comprehensive dementia care. Through a consensus-driven process, we produced a report that presents actionable recommendations to improve post-diagnostic care and payment policies under traditional Medicare.[i] [i] Nora Super, Rajiv Ahuja, and Mac McDermott," Milken Institute, November 2021: https://milkeninstitute.org/report/dementia-care-models-scaling-comprehensive RESULT: Based on extensive desktop research, the roundtable convening, and consultation with a working group of experts, we identified five high potential action steps. 1. Ensure all dementia-care models contain a minimum set of core elements for comprehensive care and follow a population-health approach that tiers services to level of need 2. Implement quality measures to evaluate access, utilization, and outcomes of comprehensive dementia-care models, particularly for diverse communities disproportionately impacted by dementia and their caregivers 3. Expand dementia-specific training beyond physicians and nurses to increase interprofessional coordination, provide continuous monitoring and assessment, and expand access to high-quality, dementia-care services 4. Test implementation of payment models for comprehensive dementia care in traditional Medicare, especially in underserved communities. 5. Develop mechanisms to pay community-based organizations (CBOs) for services provided to individuals living with dementia and their caregivers. Alternative payment models are needed under traditional Medicare to incentivize providers to coordinate care, pay CBOs for the services they provide, align incentives among payers, providers, and patients, and ensure those living with dementia and their caregivers receive more seamless, coordinated health- and long-term care.

Physical Activity Trajectories, Autonomic Balance and Cognitive Function: the CARDIA Study

AbstractBackgroundPhysical activity (PA), and particularly moderate to vigorous intensity PA (MVPA), may protect against cognitive decline. However, the underlying mechanisms are not fully understood. Cardiac autonomic balance is influenced by PA and implicated in dementia pathogenesis. Therefore, the study aimed to examine whether autonomic balance mediates the association between PA and cognitive function.MethodThe sample included 1,939 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study. MVPA was obtained in 7 consecutive examinations from baseline (1985‐86; 18‐30 years) to the Year 20 exam. Cardiac autonomic balance was assessed at Year 20 via resting heart rate, and via measures of heart rate variability: standard deviation normal to normal (SDNN) and root mean square of successive differences (RMSDD). A comprehensive cognitive assessment was performed at Year 30. Group‐based trajectory modeling was used to identify homogenous MVPA trajectory groups, and formal mediation analysis was used to test whether cardiac autonomic function indices lie on the causal pathway between MVPA trajectories and cognitive function.ResultThree distinct PA trajectory patterns were identified: (1) Below MVPA guidelines (n = 1,122; 57.9%); (2) Meeting MVPA guidelines (n = 652; 33.6%); and (3) Exceeding MVPA guidelines (n = 165; 8.5%) (Figure). Meeting and exceeding MVPA guidelines were related to lower resting heart rate and higher heart rate variability, which indicate improved autonomic balance. Meeting and exceeding MVPA guidelines were additionally associated with improved semantic fluency performance. The association between higher MVPA level and semantic fluency performance was fully mediated by RMSDD and partially mediated by SDNN. No additional associations were observed between MVPA trajectories and other cognitive outcomes, and no statistically significant mediation by autonomic balance indices was found for these associations (Table).ConclusionHigher MVPA levels across the young adult to midlife transition were associated with better cardiac autonomic function, which in turn explained some of the associations between PA trajectories and better semantic fluency performance. Future studies, particularly among older individuals are warranted to clarify the role of autonomic balance in the link between physical activity and brain health. These findings may lead to more targeted PA recommendations across the life‐course to slow cognitive decline and decrease dementia risk.

Eisai to seek FDA approval for lecanemab, one of dozens of drugs in the Alzheimer pipeline

This fall, biotech Biogen and pharmaceutical company Eisai released topline data on their new antiamyloid monoclonal antibody le-canemab. In the confirmatory phase 3 Clarity AD study, a double-blind, placebo-controlled clinical trial that included 1,795 participants with mild cognitive impairment and early Alzheimer disease (AD), the drug slowed cognitive decline by 27% over 18 months compared to placebo.

Targeting the Correct Population for Trials: A Post‐hoc Analysis of Trial of Solanezumab for Mild Dementia Due to Alzheimer’s disease.

AbstractBackgroundUp to 50% of placebo treated participants in AD clinical trials do not show clinically meaningful cognitive decline (CMCD) over the course of study. Inclusion of these individuals makes it more difficult to demonstrate the benefits of treatments intended to slow cognitive decline. Here, we used data from the trial of solanezumab for mild AD (EXPEDITION3) to investigate effectiveness of predictive models for enrichment of trials.MethodA total of 1072 patients with mild dementia and biomarker evidence of amyloid by PET or CSF studies were enrolled in the placebo arm of EXPEDITION3 trial. 893 patients completed the trial and had baseline structural MRIs making them eligible for this analysis. We identified cognitive decliners, individuals with CMCD, based on the score of the 14‐item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS‐cog14; Range 0‐90; change of ≥4 from baseline to week 80) versus stable cognition, individuals without CMCD (change of &lt;4 from baseline to week 80). Random forest classifiers were trained to classify participants into cognitive decliners vs. stable cognition groups using 3 feature‐sets: Model‐1) Demographics + Neuropsychological test (NP); Model‐2) Demographics + biomarkers (APOE4 alleles and volumetric MRI); Model‐3) All available measures. 70% of data was used for training and 30% for validation.ResultSample characteristics are summarized in Table 1. CMCD was observed in 55.8% of participants at week 80. In the validation sample, model 2 had the best performance in differentiating the two subgroups (AUC = 0.70), followed by model 3 (AUC = 0.68). Model 1 had poor performance in differentiating the two subgroups with AUC = 0.56. Table 2 summarizes performance metrics of models. Positive predictive value of the best performing model (model 2) was approximately 12% higher than the base prevalence of cognitive decline, and negative predictive value of it was approximately 20% higher than the base prevalence of participants who had stable cognition.ConclusionA large portion of biomarker confirmed AD cases enrolled in this trial did not show CMCD on placebo treatment. Predictive models have the potential to improve the design of AD trials through selective inclusion criteria for participants expected to decline and exclusion of those expected to remain stable.