Slower Rate Of Cognitive Decline Research Articles

Evaluation of a dietary screener: the Mediterranean Eating Pattern for Americans tool.

Evidence exists for an association between accordance with a Mediterranean diet pattern and slower rates of cognitive decline. However, an 'Americanised' version of the Mediterranean diet screener is needed to assess accordance in the USA. Thus, the Mediterranean Eating Pattern for Americans (MEPA) tool was developed to assess accordance with a Mediterranean-like food pattern when time is limited. The present study aimed to determine whether the MEPA screener captured the key elements of the Mediterranean diet compared to the more comprehensive food frequency questionnaire (FFQ). The study comprised a cross-sectional study in which 70 women completed both the VioScreen™ FFQ (Viocare, Princeton, NJ, USA) electronically and the 16-item MEPA screener, either electronically or by telephone, aiming to evaluate the inter-method reliability of the proposed screener. The convenience sample included patients (n = 49) and healthcare providers (n = 21) recruited from a tertiary care medical centre. The overall score from the MEPA screener correlated with corresponding overall MEPA FFQ score (ρ = 0.365, P = 0.002). Agreement between screener items and FFQ items was moderate-to-good for berries (κ = 0.47, P < 0.001), nuts (κ = 0.42, P < 0.001), fish (κ = 0.62, P < 0.001) and alcohol (κ = 0.64, P < 0.001), whereas those for olive oil (κ = 0.33, P = 0.001) and green leafy vegetables (κ = 0.36, P = 0.0021) were fair. Usual intakes of potassium, magnesium, vitamin C, saturated fat, selected carotenoids, folate and fibre derived from the FFQ varied with MEPA screener scores in the anticipated directions. The MEPA screener captures several components of the Mediterranean style pattern, although further testing of the MEPA screener is indicated.

Asymptomatic Alzheimer disease: Defining resilience.

To define robust resilience metrics by leveraging CSF biomarkers of Alzheimer disease (AD) pathology within a latent variable framework and to demonstrate the ability of such metrics to predict slower rates of cognitive decline and protection against diagnostic conversion. Participants with normal cognition (n = 297) and mild cognitive impairment (n = 432) were drawn from the Alzheimer's Disease Neuroimaging Initiative. Resilience metrics were defined at baseline by examining the residuals when regressing brain aging outcomes (hippocampal volume and cognition) on CSF biomarkers. A positive residual reflected better outcomes than expected for a given level of pathology (high resilience). Residuals were integrated into a latent variable model of resilience and validated by testing their ability to independently predict diagnostic conversion, cognitive decline, and the rate of ventricular dilation. Latent variables of resilience predicted a decreased risk of conversion (hazard ratio < 0.54, p < 0.0001), slower cognitive decline (β > 0.02, p < 0.001), and slower rates of ventricular dilation (β < -4.7, p < 2 × 10-15). These results were significant even when analyses were restricted to clinically normal individuals. Furthermore, resilience metrics interacted with biomarker status such that biomarker-positive individuals with low resilience showed the greatest risk of subsequent decline. Robust phenotypes of resilience calculated by leveraging AD biomarkers and baseline brain aging outcomes provide insight into which individuals are at greatest risk of short-term decline. Such comprehensive definitions of resilience are needed to further our understanding of the mechanisms that protect individuals from the clinical manifestation of AD dementia, especially among biomarker-positive individuals.

Adherence to a Mediterranean-Style Diet and Effects on Cognition in Adults: A Qualitative Evaluation and Systematic Review of Longitudinal and Prospective Trials.

The Mediterranean-style diet (MedDiet) involves substantial intake of fruits, vegetables, and fish, and a lower consumption of dairy, red meat, and sugars. Over the past 15 years, much empirical evidence supports the suggestion that a MedDiet may be beneficial with respect to reducing the incidence of cardiovascular disease, cancer, metabolic syndrome, and dementia. A number of cross-sectional studies that have examined the impact of MedDiet on cognition have yielded largely positive results. The objective of this review is to evaluate longitudinal and prospective trials to gain an understanding of how a MedDiet may impact cognitive processes over time. The included studies were aimed at improving cognition or minimizing of cognitive decline. Studies reviewed included assessments of dietary status using either a food frequency questionnaire or a food diary assessment. Eighteen articles meeting our inclusion criteria were subjected to systematic review. These revealed that higher adherence to a MedDiet is associated with slower rates of cognitive decline, reduced conversion to Alzheimer’s disease, and improvements in cognitive function. The specific cognitive domains that were found to benefit with improved Mediterranean Diet Score were memory (delayed recognition, long-term, and working memory), executive function, and visual constructs. The current review has also considered a number of methodological issues in making recommendations for future research. The utilization of a dietary pattern, such as the MedDiet, will be essential as part of the armamentarium to maintain quality of life and reduce the potential social and economic burden of dementia.

Self-Reported Change in Quality of Life with Retirement and Later Cognitive Decline: Prospective Data from the Nurses' Health Study.

To investigate whether a positive transition into retirement may be associated with later cognitive aging, we included a subset of 4,926 Nurses' Health Study participants who retired from work at ages 60-69, then provided a subjective assessment of the change in overall quality of life (QOL) with retirement. Subsequently (range: 1 month to 4.7 years later), when all were aged 70+ years, they completed a baseline telephone cognitive battery evaluating global cognition, episodic memory, and executive function. They had up to three follow-up cognitive assessments. Controlling for various occupational factors before retirement and socioeconomic, lifestyle, and health-related factors as of the baseline cognitive assessment, we used generalized linear models for repeated measures to estimate mean differences in rates of cognitive decline across categories of QOL transition at retirement: "worse", "same", or "better". Over a median 6 years of follow-up, the global cognitive score change was -0.123 on average. Compared with women who reported no change in QOL at retirement (31%), women who reported improvement (61%) showed a significantly slower rate of cognitive decline (difference = +0.011 95% CI = 0.004, 0.019). This mean difference was equivalent to that observed between women who were 2 years apart in age. No significant differences in cognitive decline rates were observed for the women who reported worsened QOL (8%). Secondary analyses to address possible reverse causation showed robust associations. A positive transition into retirement was associated with better maintenance of cognitive function over time in aging women. These findings need to be replicated in other populations.

Occupational cognitive requirements and late-life cognitive aging.

To examine whether occupational cognitive requirements, as a marker of adulthood cognitive activity, are associated with late-life cognition and cognitive decline. Main lifetime occupation information for 7,637 participants aged >65 years of the Chicago Health and Aging Project (CHAP) was linked with standardized data on worker attributes and job characteristics from the Occupational Information Network (O*NET). Ratings of cognitive processes required in 10 work-related tasks were used to create a summary measure of occupational cognitive requirements (possible range 0-7). Multivariable-adjusted linear mixed models were used to estimate the association of occupational cognitive requirements score (OCRS) with cognitive function and rate of cognitive decline. Higher OCRS corresponded to significantly better late-life cognitive performance at baseline in 1993 (p < 0.001) and to slower decline in global cognitive function over time (p = 0.004). Within a genotyped subsample (n = 4,104), the associations of OCRS with rate of cognitive decline did not differ significantly by APOE ε4 carriership (p = 0.11). Findings suggest that occupational cognitive requirements are associated with better cognition and a slower rate of cognitive decline in older age. Adulthood cognitive activity may contribute to cognitive reserve in late life.

Dietary Patterns and Cognitive Decline Among Chinese Older Adults.

Prospective evidence of associations of dietary patterns with cognitive decline is limited and inconsistent. We examined how cognitive changes among Chinese older adults relate to either an adapted Mediterranean diet score or factor analysis-derived dietary patterns. This prospective cohort study comprised 1,650 adults ≥55 years of age, who completed a cognitive screening test at two or more waves of the China Health and Nutrition Survey in 1997, 2000, or 2004. Outcomes were repeated measures of global cognitive scores, composite cognitive z scores (standardized units [SU]), and standardized verbal memory scores (SU). Baseline diet was measured by 24-hour recalls over 3 days. We used linear mixed effects models to evaluate how changes in cognitive scores were associated with adapted Mediterranean diet score and two dietary pattern scores derived from factor analysis. Among adults ≥65 years of age, compared with participants in the lowest tertile of adapted Mediterranean diet, those in the highest tertile had a slower rate of cognitive decline (difference in mean SU change/year β = 0.042; 95% confidence interval [CI]: 0.002, 0.081). A wheat-based diverse diet derived by factor analysis shared features of the adapted Mediterranean diet, with the top tertile associated with slower annual decline in global cognitive function (β = 0.069 SU/year; 95% CI: 0.023, 0.114). We observed no associations among adults <65 years of age. Our findings suggest that an adapted Mediterranean diet or a wheat-based, diverse diet with similar components may reduce the rate of cognitive decline in later life in the Chinese population.

Cognitive decline and the neighborhood environment

PurposeLittle research has looked beyond individual factors to consider the influence of the neighborhood environment on cognitive function. A greater density of physical resources (e.g., recreational centers and parks) and institutional resources (e.g., community centers) may buffer cognitive decline by offering opportunities for physical activity and social interaction. MethodsUsing data from the Chicago Health and Aging Project (1993–2011), a prospective cohort study of 6518 adults of age 65 years or older, we fit a three-level growth curve model to examine the role of individual and neighborhood factors (objectively observed at the block group level) on trajectories of cognitive function (composite of East Boston Memory Test, symbol digit test, and Mini Mental State Examination) in later life. ResultsNet of individual factors, residence in a neighborhood with community resources, proximity to public transit, and public spaces in good condition were associated with slower rates of cognitive decline, possibly by increasing opportunities for social and physical activities or access to destinations that facilitate engagement in activities. ConclusionsThese results highlight the role of neighborhood environments in buffering cognitive decline among older adults aging in place.

Relations to Cognitive Change with Age of Micronutrients Found in Green Leafy Vegetables

Consumption of green leafy vegetables has been reported to reduce cognitive decline in older adults. We investigated the relations to cognitive decline of various micronutrients for which green leafy vegetables are a rich dietary source, including phylloquinone (vitamin K), folate and carotenoids (lutein, lycopene, beta‐cryptoxanthin, alph carotene, beta carotene), in a cohort study of 954 participants of the Memory and Aging Project, mean age 81 years, 75% female. Diet was assessed by a 144‐item semi‐quantitative food frequency questionnaire. Energy‐adjusted nutrients were modeled in quintiles. Cognition was assessed annually by a battery of 19 tests. Nutrient intakes were related to change in cognitive function over a mean 4.5 years using linear‐mixed models adjusted for age, sex, education, and participation in cognitive activities. Higher green leafy vegetable consumption was associated with slower cognitive decline (β=0.033, SE=0.010, p=0.001). In analyses of micronutrients, we observed slower rates of cognitive decline for food folate (Q5 vs Q1 β=0.044, p=0.004), phylloquinone (Q5 vs Q1 β=0.040, p=0.001), lutein (Q5 vs Q1 β=0.039, p=0.001), and total beta carotene (Q5 vs Q1 β=0.029, p=0.01). No associations were observed for lycopene, alpha carotene, or beta‐cryptoxanthin. Cognitive decline in older adults may be slowed through the consumption of green leafy vegetables rich in folate, phylloquinone, lutein and beta carotene.Supported by grants R01 AG031553 and R01 AG17917

Initial cognitive response to cholinesterase inhibitors and subsequent long-term course in patients with mild Alzheimer's disease.

Some guidelines recommend to discontinue treatment with cholinesterase inhibitors (ChEIs) in patients with Alzheimer's disease (AD) without an initial response to ChEI treatment. Evidence supporting this recommendation, however, is limited. This study aimed to investigate the relation between the initial cognitive response to ChEI treatment and the subsequent long-term course of cognition of AD patients. The Frisian Alzheimer's Disease Cohort study is a retrospective longitudinal study of 576 community-dwelling AD patients treated with ChEIs in a "real-life" setting at a large memory clinic. A repeated measures analysis using a marginal model (population based averaged model) was applied to investigate whether there is a difference in the subsequent long-term course of cognition (Mini-Mental State Examination (MMSE)) between initial non-responders and responders. Absence of an initial response was defined as a lower MMSE score after the first six months of treatment compared to baseline, a positive response as the same or a higher MMSE score. At baseline, median age was 80 years and the median MMSE score 23. Non-responders showed a slower rate of cognitive decline in the three subsequent years than responders, with a mean annual MMSE decline of 0.9 points versus 1.2 points, respectively (p < 0.0001). Our results suggest that it is not appropriate to discontinue ChEI treatment solely based on the absence of an initial cognitive response.

Early life instruction in foreign language and music and incidence of mild cognitive impairment.

To test the hypothesis that foreign language and music instruction in early life are associated with lower incidence of mild cognitive impairment (MCI) and slower rate of cognitive decline in old age. At enrollment in a longitudinal cohort study, 964 older persons without cognitive impairment estimated years of foreign language and music instruction by age 18. Annually thereafter they completed clinical evaluations that included cognitive testing and clinical classification of MCI. There were 264 persons with no foreign language instruction, 576 with 1-4 years, and 124 with > 4 years; 346 persons with no music instruction, 360 with 1-4 years, and 258 with > 4 years. During a mean of 5.8 years of observation, 396 participants (41.1%) developed MCI. In a proportional hazards model adjusted for age, sex, and education, higher levels (> 4 years) of foreign language (hazard ratio [HR] = 0.687, 95% confidence interval [CI] [0.482, 0.961]) and music (HR = 0.708, 95% CI [0.539, 0.930]) instruction by the age of 18 were each associated with reduced risk of MCI. The association persisted after adjustment for other early life indicators of an enriched cognitive environment, and it was stronger for nonamnestic than amnestic MCI. Both foreign language and music instruction were associated with higher initial level of cognitive function, but neither instruction measure was associated with cognitive decline. Higher levels of foreign language and music instruction during childhood and adolescence are associated in old age with lower risk of developing MCI but not with rate of cognitive decline.

Impact of renin-angiotensin system-targeting antihypertensive drugs on treatment of Alzheimer's disease: a meta-analysis.

The impacts of renin-angiotensin system (RAS)-targeting antihypertensive drugs on Alzheimer's disease (AD) remain controversial. We performed this meta-analysis to evaluate the precise value of RAS-targeting antihypertensive drugs in terms of attenuating incidence of AD and slowing down cognitive decline in patients with AD. A systematic literature search was conducted using PubMed, Embase, ScienceDirect and CBM (China Biology Medicine Disc) before September 2014. Studies analysing incidence of AD and cognitive changes in AD patients with RAS-targeting antihypertensive drugs were identified. The principal outcome measures were hazard ratios (HRs) for incidence of AD and standardised mean difference (SMD) for cognitive changes in AD patients. Pooled data were calculated using fixed or random effects models according to the heterogeneity. In total, 12 studies involving 896,410 participants met our inclusion criteria. RAS-targeting antihypertensive drugs were significantly associated with a reduced incidence rate of AD (HR 0.81, 95% CI 0.72-0.92, p = 0.001). In subgroup analysis, both angiotensin renin blockers and angiotensin converting enzyme inhibitors were shown to effectively decrease the incidence rate of AD. In the analysis of cognitive changes, a slower rate of cognitive decline was observed in AD patients with RAS-targeting antihypertensive drug (SMD 0.30, 95% CI 0.09-0.50, p = 0.004), when randomised trials and observational trials were combined. However, analysis of randomised trials alone did not show the same result (SMD 0.20, 95% CI -0.10 to 0.50, p = 0.182). Renin-angiotensin system-targeting antihypertensive drugs may be a potential treatment for reducing the incidence and progression of AD. Further studies on RAS-targeting antihypertensive drugs, especially large randomised clinical trials, should be conducted in the future.

Intensive glycaemic control and cognitive decline in patients with type 2 diabetes: a meta-analysis.

The aim of this meta-analysis was to compare the effect of intensive vs standard glycaemic control on cognitive decline in type 2 diabetic patients. A systematic search of PubMed and ALOIS was conducted from inception up to October 30, 2014. Randomised controlled trials (RCTs) of type 2 diabetic patients comparing the rate of change in cognitive function among participants assigned to intensive vs standard glycaemic control were included. An inverse-variance-weighted random effects model was used to calculate standardised mean differences (SMDs) and 95% CIs. A total of 24 297 patients from five RCTs were included in the meta-analysis. Follow-up ranged from 3.3 to 6.2 years. The result from the pooled analysis showed that intensive glycaemic control was not associated with a slower rate of cognitive decline in patients with type 2 diabetes, compared with standard glycaemic control (SMD=0.02; 95% CI=−0.03 to 0.08) although there was some heterogeneity across individual studies (I 2=68%, P for heterogeneity=0.01). There are few diabetes control trials including cognitive endpoints and a small number of trials comparing intensive and standard treatment strategies. Currently, intensive glycaemic control should not be recommended for prevention of cognitive decline in patients with type 2 diabetes because there is no evidence of its effectiveness. Moreover, the use of intensive diabetes treatment results in an increase of risk of hypoglycaemia, which is linked to a greater risk of poor cognition.

Components of late-life exercise and cognitive function: an 8-year longitudinal study.

The preventive effect of late-life physical exercise on cognitive deterioration has been reported in many cohort studies. However, the effect of exercise, independent of other cognitively demanding and social activities, is equivocal and little is known about the relative contributions of frequency, intensity, and duration of exercise. This study aimed to examine the relationships of exercise and its underlying components with cognitive function and rate of cognitive change over an 8-year period in a nationally representative sample of older Taiwanese. Data from the 1999, 2003, and 2007 phases of the nationwide longitudinal survey were used. Data from a fixed cohort of 1,268 participants aged 70 years or older in 1999 with 8 years of follow-up were analyzed. Cognitive function was assessed using the Short Portable Mental Status Questionnaire. Self-reported frequency, intensity, and duration of exercise were collected. A generalized estimating equation with multivariate adjustment for sociodemographic variables, cognitive and social leisure activities, lifestyle behaviors, and health status was calculated. Participants who were physically active during leisure time had better subsequent cognitive function (incident rate ratios [IRR] = 0.63; 95 % CI, 0.54-0.75) and a slower rate of cognitive decline (p = 0.01). Among the components of exercise, only duration emerged as a predictor of cognitive function (p = 0.01). Older adults engaging in exercise for at least 30 min or more per session are likely to reduce the risk of subsequent cognitive decline. This research supports the case for physical exercise programs for older adults in order to help prevent loss of cognitive function.

Relation of DASH- and Mediterranean-like dietary patterns to cognitive decline in older persons.

We examined whether accordance to the DASH (Dietary Approach to Stop Hypertension) and Mediterranean diets is associated with slower cognitive decline in a prospective Chicago cohort study of older persons, the Memory and Aging Project. The sample comprised 826 Memory and Aging Project participants (aged 81.5 ± 7.1 years) who completed a 144-item food frequency questionnaire at baseline and 2 or more cognitive assessments over 4.1 years. Dietary scores were computed for accordance to the DASH diet (0-10) and the Mediterranean diet (MedDietScore) (0-55). For both, higher scores reflect greater accordance. Both patterns share at least 3 common food components. Cognitive function was assessed annually with 19 cognitive tests from which global cognitive scores and summary measures are computed. The mean global cognitive score at baseline was 0.12 (range, -3.23 to 1.60) with an overall mean annual change in score of -0.08 standardized units. Only 13 participants had possible dementia. The mean DASH score was 4.1 (range, 1.0-8.5) and the MedDietScore was 31.3 (range, 18-46). In mixed models adjusted for covariates, a 1-unit difference in DASH score was associated with a slower rate of global cognitive decline by 0.007 standardized units (standard error of estimate = 0.003, p = 0.03). Similarly, a 1-unit-higher MedDietScore was associated with a slower rate of global cognitive decline by 0.002 standardized units (standard error of estimate = 0.001, p = 0.01). These findings support the hypothesis that both the DASH and Mediterranean diet patterns are associated with slower rates of cognitive decline in the same cohort of older persons.

Differential clinicopathologic and genetic features of late-onset amnestic dementias.

Hippocampal sclerosis of the elderly (HpScl) and Alzheimer's disease (AD), especially the limbic-predominant subtype (LP-AD), are amnestic syndromes that can be difficult to distinguish. To complicate matters, a subset has concomitant HpScl and AD (HpScl-AD). We examined a large cohort of autopsy-confirmed cases of HpScl, HpScl-AD, LP-AD, and typical AD to identify distinct clinical, genetic, and pathologic characteristics. HpScl cases were significantly older at death and had a substantially slower rate of cognitive decline than the AD subtypes. Genetic analysis revealed that the AD groups (AD, LP-AD, and HpScl-AD) were more likely to be APOE ε4 carriers. In contrast, the HpScl groups (HpScl and HpScl-AD) were more likely to exhibit genetic variants in GRN and TMEM106B that are associated with frontotemporal lobar degeneration. The HpScl groups had a high frequency of TDP-43 pathology that was most often Type A morphology and distribution, while typical AD and LP-AD had a significantly lower frequency of TDP-43 pathology that was most often Type B. These results suggest that HpScl and AD are pathologically and genetically distinct and non-synergistic neurodegenerative processes that present with amnestic dementia. Pure HpScl and HpScl with concomitant AD occur most often in elderly individuals.

Abstract P185: Fish Intake is Associated with Slower Cognitive Decline in Chinese Older Adults: a Longitudinal Study from the China Health and Nutrition Survey

Introduction: With global population aging, identifying public health strategies to prevent or reduce cognitive decline is of increasing importance. This study explores the potential role of a modifiable dietary behavior, fish consumption, to reduce the rate of cognitive decline in a cohort of Chinese older adults. Methods: This study comprised adults aged ≥55 who completed a brief cognitive screening test at two or more waves of the China Health and Nutrition Survey (CHNS) from 1997 to 2004. The cognitive screening test had a maximum of 31 points and assessed immediate and delayed memory, attention, calculation, and orientation. Diet was measured by 3-day 24-hour recalls. Multivariable-adjusted linear mixed-effects models were used to evaluate the relation of fish intake at baseline with changes in cognitive scores, adjusting for age, gender, region, urbanization index, education, household income, energy intake, physical activity, current alcohol use, current smoking, and consumption of fresh vegetables, fruits, fresh legumes, and high-fat meat, as well as time, and time interactions with each covariate. Based on the distribution of fish intake, we compared consumption ≥1 vs. &lt;1 serving/week. Sensitivity analysis included 1) removing shellfish and/or preserved fish; 2) exploring potential confounding by or interactions with hypertension or body mass index; 3) excluding those with the lowest 10% baseline cognitive scores; 4) adjusting for dietary patterns to determine if associations were independent of overall eating patterns; 5) using propensity score analysis to ensure comparability of the fish intake groups. Results: The average follow-up among 1566 older adults was 5.3 years, with a mean annual rate of decline 0.40 points. Since age significantly modified the fish-cognitive change association (p=0.003), we stratified analysis by adults &lt;65 (n=968) at first measure, and ≥65 (n=598). No significant associations were found among adults &lt;65. Among adults ≥65, compared with persons who consumed fish &lt;1 serving/week, the average rate of global cognitive decline was reduced by 0.35 points per year or 55% (p = 0.001) among those consuming fish ≥1 serving/week. Results remained consistent in sensitivity analysis. When the cognitive test items were analyzed based on the domain assessed, fish intake was associated with a significantly slower rate of decline in memory scores among adults ≥65. The average rate of memory decline was reduced by 60% among persons who consumed fish ≥1 serving/week. Conclusions: Fish intake of at least 1 serving per week predicted a slower rate of cognitive decline among Chinese adults ≥65 years old, particularly for immediate and delayed memory. The cognitive benefits of fish intake were not apparent among Chinese adults aged 55 to 64. This is the first study in Chinese older adults to evaluate the role of fish consumption on cognitive decline.

Mental work demands, retirement, and longitudinal trajectories of cognitive functioning.

Age-related changes in cognitive abilities are well-documented, and a very important indicator of health, functioning, and decline in later life. However, less is known about the course of cognitive functioning before and after retirement and specifically whether job characteristics during one's time of employment (i.e., higher vs. lower levels of mental work demands) moderate how cognition changes both before and after the transition to retirement. We used data from n = 4,182 (50% women) individuals in the Health and Retirement Study, a nationally representative panel study in the United States, across an 18 year time span (1992-2010). Data were linked to the O*NET occupation codes to gather information about mental job demands to examine whether job characteristics during one's time of employment moderates level and rate of change in cognitive functioning (episodic memory and mental status) both before and after retirement. Results indicated that working in an occupation characterized by higher levels of mental demands was associated with higher levels of cognitive functioning before retirement, and a slower rate of cognitive decline after retirement. We controlled for a number of important covariates, including socioeconomic (education and income), demographic, and health variables. Our discussion focuses on pathways through which job characteristics may be associated with the course of cognitive functioning in relation to the important transition of retirement. Implications for job design as well as retirement are offered.

Food for Thought: Hypertension-Control Diet Also Slowed Cognitive Decline

Food for Thought: Hypertension-Control Diet Also Slowed Cognitive Decline

Neural reserve, neuronal density in the locus ceruleus, and cognitive decline.

To test the hypothesis that higher neuronal density in brainstem aminergic nuclei contributes to neural reserve. Participants are 165 individuals from the Rush Memory and Aging Project, a longitudinal clinical-pathologic cohort study. They completed a mean of 5.8 years of annual evaluations that included a battery of 19 cognitive tests from which a previously established composite measure of global cognition was derived. Upon death, they had a brain autopsy and uniform neuropathologic examination that provided estimates of the density of aminergic neurons in the locus ceruleus, dorsal raphe nucleus, substantia nigra, and ventral tegmental area plus summary measures of neuronal neurofibrillary tangles and Lewy bodies from these nuclei and medial temporal lobe and neocortex. Neuronal densities in each nucleus were approximately normally distributed. In separate analyses, higher neuronal density in each nucleus except the ventral tegmental area was associated with slower rate of cognitive decline, but when modeled together only locus ceruleus neuronal density was related to cognitive decline (estimate = 0.003, SE = 0.001, p < 0.001). Higher densities of tangles and Lewy bodies in these brainstem nuclei were associated with faster cognitive decline even after controlling for pathologic burden elsewhere in the brain. Locus ceruleus neuronal density, brainstem tangles, and brainstem Lewy bodies had independent associations with rate of cognitive decline. In addition, at higher levels of locus ceruleus neuronal density, the association of Lewy bodies with cognitive decline was diminished. Density of noradrenergic neurons in the locus ceruleus may be a structural component of neural reserve.

Progression of mild Alzheimer’s disease: knowledge and prediction models required for future treatment strategies

IntroductionKnowledge of longitudinal progression in mild Alzheimer’s disease (AD) is required for the evaluation of disease-modifying therapies. Our aim was to observe the effects of long-term cholinesterase inhibitor (ChEI) therapy in mild AD patients in a routine clinical setting.MethodsThis was a prospective, open-label, non-randomized, multicenter study of ChEI treatment (donepezil, rivastigmine or galantamine) conducted during clinical practice. The 734 mild AD patients (Mini-Mental State Examination (MMSE) score 20 to 26) were assessed at baseline and then semi-annually over three years. Outcome measures included the MMSE, Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), Clinician’s Interview-Based Impression of Change (CIBIC) and Instrumental Activities of Daily Living (IADL) scale.ResultsAfter three years of ChEI therapy, 31% (MMSE) and 33% (ADAS-cog) of the patients showed improved/unchanged cognitive ability, 33% showed improved/unchanged global performance and 14% showed improved/unchanged IADL capacity. Higher mean dose of ChEI and lower educational level were both predictors of more positive longitudinal cognitive and functional outcomes. Older participants and those with a better IADL score at baseline exhibited a slower rate of cognitive decline, whereas younger participants and those with higher cognitive status showed more preserved IADL ability over time. Gender and apolipoprotein E (APOE) genotype showed inconsistent results. Prediction models using the abovementioned scales are presented.ConclusionsIn naturalistic mild AD patients, a marked deterioration in IADL compared with cognitive and global long-term outcomes was observed, indicating the importance of functional assessments during the early stages of the disease. The participants’ time on ChEI treatment before inclusion in studies of new therapies might affect their rate of decline and thus the comparisons of changes in scores between various studies. An increased understanding of expected disease progression in different domains and potential predictors of disease progression is essential for assessment of future therapies in AD.