Risk Of Future Cognitive Impairment Research Articles

Effect of vigorous-intensity physical activity on incident cognitive impairment in high-risk hypertension.

We investigated the effect vigorous physical activity (VPA) on the risk of incident mild cognitive impairment (MCI) and probable dementia among individuals with high-risk hypertension. Baseline self-reported frequency of VPA was categorized into low VPA (<1 session/week), and high VPA (≥1 session/week). We used multivariate Cox regression analysis to examine the association of VPA categories with incident MCI and probable dementia events. Participants in the high VPA category, compared with low VPA, experienced lower events rates (per 1000 person-years) of MCI (13.9vs 19.7), probable dementia (6.3vs 9.0), and MCI/probable dementia (18.5vs 25.8). In the multivariate Cox regression model, high VPA, compared with low VPA, was associated with lower risk of MCI, probable dementia, and MCI/probable dementia (HR [95% CI]: 0.81 [0.68-0.97], 0.80 [0.63-1.03], and 0.82 [0.70-0.96]), respectively. This study provides evidence that VPA may preserve cognitive function in high-risk patients with hypertension. Hypertension is associated with an increased risk of cognitive impairment Physical activity (PA) is associated with a lower risk of decline in cognition The effect of ≥1 sessions of vigorous-intensity PA (VPA) per week was assessed This analysis included SPRINT MIND trial participants with high-risk hypertension ≥1 VPA sessions/week was associated with lower risk of future cognitive impairment.

ASSOCIATIONS OF NIGHT AND DAY SLEEP WITH COGNITIVE PERFORMANCE IN SHIFT WORKERS: PRELIMINARY RESULTS

Abstract Emerging evidence suggests that night shift workers are at higher risk of severe cognitive impairment, mainly because of the repeated disruption of the sleep–wake schedule and the resulting poor sleep (e.g., less deep sleep or shorter sleep time). However, questions remain about how daytime and nighttime sleep characteristics correlate with cognitive performance in shift workers. The purpose of this study is to examine the association of objective sleep quality, measured on workdays and days off, with cognitive performance, determined by the psychomotor vigilance task (PVT), in shift workers compared to day workers. We included eight night shift and ten day shift workers from an ongoing pilot study in this analysis. Participants undergo multiple home sleep studies with electroencephalograms on their workdays or days off. Sleep quality measures include total sleep time (TST), percentage of deep sleep stage in TST, and wake time after sleep onset (WASO). Night shift workers showed longer TST and shorter WASO during their nighttime sleep on days off compared to day shift workers. In night shift workers, longer deep sleep on days off was significantly correlated with faster mean reaction time to a visual stimulus (better cognitive performance) on the PVT (r = -.944, p = .016), after controlling for age. However, longer deep sleep during their daytime sleep was associated with slower reaction time (r = .756, p = .049). Further studies are necessary to elucidate differential impacts of daytime and nighttime sleep on the risk of future cognitive impairment in night shift workers.

Degeneration of the cholinergic system in subjective cognitive decline: A systematic review

AbstractBackgroundSubjective cognitive decline (SCD) is topic of mayor interest when identifying individuals at risk for future cognitive impairment and dementia. The degeneration of the cholinergic system is linked to the onset of cognitive symptoms in mild cognitive impairment (MCI) and dementia. Yet, it is uncertain whether the neurodegeneration of the cholinergic system is already present in SCD individuals. This review is the first to synthetize the available data on the association of SCD with multiple markers of degeneration in the cholinergic system.MethodFollowing the PRISMA guidelines, original articles focused on the association of SCD and the cholinergic system were extracted from three databases: Pubmed, WOS and Scopus, in November 2021. Two researchers reviewed the studies independently in a 2‐stepwise approach. The quality of the studies and risk of bias were assessed using FLC 3.0, that allows to systematically evaluate the studies and summarize them easily.ResultAmong 119 studies found in our systematic search, 11 were included in the current review. Seven were cross‐sectional and 4 had a longitudinal design. Most of the studies operationalized SCD based on amnestic cognitive complaints (n = 9, 82%). The cholinergic system measures were based on neuroimaging markers for volume of the basal forebrain and/or functional connectivity, transcranial magnetic stimulation, or biofluid markers (i.e. cerebrospinal fluid (CSF) and plasma). The studies focused on association of SCD with basal brain atrophy, 75% reported reduce volumes in SCD; From those focused on functional connectivity of the cholinergic system, 33% reported poorer connectivity in SCD.ConclusionBased on scientific evidence, neurodegeneration of the cholinergic system is already evident during SCD. Using multiple cholinergic biomarkers, degeneration of cholinergic system in SCD seems to occur with significant structural and functional degeneration of cholinergic nuclei in the basal forebrain and their connections with other brain areas. These findings have implications on identifying individuals with increased vulnerability to cognitive impairment and for targeting individuals that might benefit from cholinergic‐target treatments. Further research is needed to elucidate potential contributors to the cholinergic degeneration in SCD and its impact on cognition and clinical progression.

Longitudinal Relationship Between Handgrip Strength and Cognitive Function in a European Multicentric Population Older Than 50Years.

The aim of this study was to analyze the bidirectional association between handgrip strength (HGS) and cognitive performance in different cognitive functions in a European population and to evaluate the predictive validity of HGS for the risk of future cognitive impairment in aging individuals. This was a prospective cohort study conducted using data on individuals over 50years of age from the Survey of Health, Aging and Retirement in Europe (SHARE). HGS measures and scores in numeracy, recall, and verbal fluency were repeated and analyzed biannually for 4years and were used in generalized estimating equations to test the bidirectional association, categorized by sex. Of the 8236 individuals included, 55.73% were women with a mean age of 67.55 (standard deviation [SD] = 8.4) years and 44.27% were men with a mean age of 68.42 (SD = 7.7) years. HGS predicted cognitive decline in both sexes, except for numeracy in men, even after adjustments. The strongest association with HGS in women was in verbal fluency (β = .094; 95% CI = 0.039 to 0.151), whereas the strongest association with HGS in men was in delayed verbal recall (β = .095; 95% CI = 0.039 to 0.151). Conversely, the greatest cognitive predictor of HGS decline was verbal fluency in men (β = .796; 95% CI = 0.464 to 1.128), and in women (β = .801; 95% CI= 0.567 to 1.109). There is a significant and bidirectional association between HGS and different cognitive functions in a European multicentric population. This bidirectional association differed between sexes. Both men and women who presented with cognitive decline also showed early changes in their HGS measures, and vice versa, but there still were differences between the sexes. These findings reinforce that HGS may be a simple and inexpensive method to identify early signs of cognitive decline, and that studies and rehabilitation strategies should be more sex specific.

Acute Effects of a Maximal Cardiopulmonary Exercise Test on Cardiac Hemodynamic and Cerebrovascular Response and Their Relationship with Cognitive Performance in Individuals with Type 2 Diabetes.

Cardiovascular and cerebrovascular diseases are prevalent in individuals with type 2 diabetes (T2D). Among people with T2D aged over 70 years, up to 45% might have cognitive dysfunction. Cardiorespiratory fitness (V˙O2max) correlates with cognitive performances in healthy younger and older adults, and individuals with cardiovascular diseases (CVD). The relationship between cognitive performances, V˙O2max, cardiac output and cerebral oxygenation/perfusion responses during exercise has not been studied in patients with T2D. Studying cardiac hemodynamics and cerebrovascular responses during a maximal cardiopulmonary exercise test (CPET) and during the recovery phase, as well as studying their relationship with cognitive performances could be useful to detect patients at greater risk of future cognitive impairment. Purposes: (1) to compare cerebral oxygenation/perfusion during a CPET and during its post-exercise period (recovery); (2) to compare cognitive performances in patients with T2D to those in healthy controls; and (3) to examine if V˙O2max, maximal cardiac output and cerebral oxygenation/perfusion are associated with cognitive function in individuals with T2D and healthy controls. Nineteen patients with T2D (61.9 ± 7 years old) and 22 healthy controls (HC) (61.8 ± 10 years old) were evaluated on the following: a CPET test with impedance cardiography and cerebral oxygenation/perfusion using a near-infrared spectroscopy. Prior to the CPET, the cognitive performance assessment was performed, targeting: short-term and working memory, processing speed, executive functions, and long-term verbal memory. Patients with T2D had lower V˙O2max values compared to HC (34.5 ± 5.6 vs. 46.4 ± 7.6 mL/kg fat free mass/min; p < 0.001). Compared to HC, patients with T2D showed lower maximal cardiac index (6.27 ± 2.09 vs. 8.70 ± 1.09 L/min/m2, p < 0.05) and higher values of systemic vascular resistance index (826.21 ± 308.21 vs. 583.35 ± 90.36 Dyn·s/cm5·m2) and systolic blood pressure at maximal exercise (204.94 ± 26.21 vs. 183.61 ± 19.09 mmHg, p = 0.005). Cerebral HHb during the 1st and 2nd min of recovery was significantly higher in HC compared to T2D (p < 0.05). Executive functions performance (Z score) was significantly lower in patients with T2D compared to HC (-0.18 ± 0.7 vs. -0.40 ± 0.60, p = 0.016). Processing speed, working and verbal memory performances were similar in both groups. Brain tHb during exercise and recovery (-0.50, -0.68, p < 0.05), and O2Hb during recovery (-0.68, p < 0.05) only negatively correlated with executive functions performance in patients with T2D (lower tHb values associated with longer response times, indicating a lower performance). In addition to reduced V˙O2max, cardiac index and elevated vascular resistance, patients with T2D showed reduced cerebral hemoglobin (O2Hb and HHb) during early recovery (0-2 min) after the CPET, and lower performances in executive functions compared to healthy controls. Cerebrovascular responses to the CPET and during the recovery phase could be a biological marker of cognitive impairment in T2D.

Do you want to know your future? A qualitative study of patient perspectives on knowing the risk of an incurable disease through ophthalmologic screening

BackgroundDementia and Alzheimer's disease are currently incurable. Evolving technology is investigating ways to diagnose cognitive impairment earlier. In the field of ophthalmology, optical coherence tomography is emerging as a noninvasive, cost-effective means of predicting the risk of future cognitive impairment in patients. ObjectiveTo explore patient perspectives and determine patients’ preferences regarding the desire for knowledge of a future risk of cognitive impairment years before the onset of any symptoms. MethodsWe conducted a qualitative study using a five-question survey distributed to seniors aged 50 and older at a senior center. ResultsOf the 210 participants, 194 (92.4%) wanted to know if they had a risk of dementia or Alzheimer's disease using retinal scanning. Of those responding “yes,” 150 (77.4%) wanted to know so that they could plan for the future. Education did not appear to have an impact on decision making. Of those with up to a high school education, 89.4% wanted to know the risk, while 94.8% of those with an education beyond high school wanted to know the risk. Of those employed in healthcare, 85.7% wanted to know about the risk of cognitive decline, and 93.1% of those employed outside of healthcare wanted to know the risk of cognitive decline. ConclusionsAn overwhelming majority of participants chose to know their future risk of cognitive impairment. Many cited “planning for the future” as the reasoning behind their choice. This study supports the idea that patients want to know more about their health risks and potential future diagnoses, so that they can make better informed decisions regarding their healthcare. The desire to know risk appears to be a universal concept, as there was not a statistically significant difference in opinion based on education or employment.

The potential protective benefit of personality on subjective cognitive decline related worry: Results from the Canadian Longitudinal Study on Aging (CLSA)

AbstractBackgroundSubjective cognitive decline (SCD), a self‐reported decline in cognition, may be a risk factor for Alzheimer’s disease. Recently, SCD‐related worry has been implicated in predicting the progression from SCD to further cognitive decline. Certain personality traits have been linked to cognitive health (i.e., conscientiousness, emotional‐stability, and openness to experience), but little is known about the association between personality traits and worry related to perceived cognitive decline.MethodAnalyzing data from the Canadian Longitudinal Study on Aging (CLSA), a large national study of participants aged 45‐85 at baseline, we sought to identify prospective psychosocial correlates of SCD‐related worry. At baseline, known correlates of cognition (e.g., depression) were measured, as well as the primary predictor of interest, personality traits, which were measured using the Ten‐Item Personality Inventory (TIPI). SCD and SCD‐related worry were measured three years later. Participants who positively endorsed SCD at follow‐up were asked a single‐item assessing their worry about their self‐reported memory decline. Response options ranged from disagree to agree. Multiple imputation using chained equations (MICE) was conducted to account for missing data. An ordinal logistic regression model was used to estimate the odds of reporting greater SCD‐related worry (n = 27,745).ResultMany psychosocial measures were associated with greater SCD‐related worry, for example, being a woman (OR = 1.35, CI: 1.25‐1.45), being younger (OR = 0.99, CI: 0.97‐0.99), and elevated depression symptoms (OR = 1.44, CI: 1.32‐1.58). With respect to personality traits, higher levels of certain traits were associated with reduced odds of SCD‐related worry: extraversion (OR = 0.96, CI: 0.95‐0.98), conscientiousness (OR = 0.95, CI: 0.92‐0.97), and emotional stability (OR = 0.86, CI: 0.84‐0.88). Openness to experience (OR = 1.01, CI: 0.99‐1.03), and agreeableness (OR = 1.00, CI: 0.97‐1.03), were not associated with SCD‐related worry.ConclusionHigher levels of extraversion, conscientiousness, and emotional stability were associated with higher worry regarding perceived decline in cognitive functioning. This information may help identify individuals at a greater risk of future cognitive impairment and dementia.

Milk fat globule membrane concentrate as a nutritional supplement prevents age-related cognitive decline in old rats: A lipidomic study of synaptosomes

Aging is associated with a decline in cognitive abilities, mainly in memory and executive functioning. A similar but premature deterioration in cognitive capacities is the hallmark of mild cognitive impairment, Alzeimer’s disease and dementia. The biochemical mechanisms that cause these neurodegenerative disorders are poorly understood. However, some evidence suggests that insufficient dietary intakes of some phospholipids could impact on brain function and increase the risk of future cognitive impairment and dementia. We evaluated the cognitive and biochemical effects of supplementation with a milk fat globule membrane (MFGM) concentrate in aged rats.We observed that, compared to control animals, MFGM supplemented rats showed enhanced spatial working memory, but both groups exhibited similar reference spatial learning and emotional memory abilities. No significant differences between BDNF levels in the hippocampus and frontal cortex of treated rats as compared to controls were found. The nootropic effects observed were accompanied by significant changes in the lipid composition of synaptic membranes. MFGM supplementation increased the levels of EPA and DHA acids as well as the plasmalogens content in the synaptosomes isolated from the hippocampus (Synapt-HP) and the frontal cortex (Synapt-FC). In addition enhanced levels of phosphatidyl serine (PS), particularly PS(18:1/18:1), and phosphatidyl inositol (PI) molecular species were observed in Synapt-HP and Synapt-FC of treated animals.Lipidomic analysis also revealed greater concentration of phosphatidyl ethanolamine (PE) molecular species containing very long-chain fatty acids and PE plasmenyls in Synapt-HP as well as an increase of the SM content in Synapt-FC from the MFGM group. Although further studies are needed to confirm the underlying mechanism (individual or synergistic), these results suggest that MFGM supplementation could be employed as a dietary implement to restore the proper cerebral concentration of some bioactive lipids and prevent or slow the progression of age-related cognitive impairment.

Subjective Impairments in Olfaction and Cognition Predict Dissociated Behavioral Outcomes.

Self-rated subjective cognitive decline (SCD) and subjective olfactory impairment (SOI) are associated with objective cognitive decline and dementia. However, their relationship and co-occurrence is unknown. We aimed to (a) describe the occurrence of SOI, SCD and their overlap in the general population; (b) compare SOI and SCD in terms of longitudinal associations with corresponding objective olfactory and cognitive measures; and (c) describe how SOI and SCD may lead to distinct sensory and cognitive outcomes. Cognitively unimpaired individuals from the third wave of the Swedish population-based Betula study (n = 784, aged 35-90 years; 51% females) were split into self-rated SOI, SCD, overlapping SCD + SOI, and controls. Between-subject and within-subject repeated-measures MANCOVA were used to compare the groups regarding odor identification, cognition, age, sex, and education. Spearman correlation was used to assess the different patterns of association between olfaction and cognition across groups. SOI was present in 21.1%, whereas SCD was present in 9.9% of participants. According to a chi-square analysis, the SCD + SOI overlap (2.7%) is on a level that could be expected if the phenomena were independent. Odor identification in SOI showed decline at the 10-year follow-up (n = 284) and was positively associated with cognition. The SOI and SCD groups showed distinct cognitive-olfactory profiles at follow-up. SOI occur independently of SCD in the population, and these risk factors are associated with different cognitive and olfactory outcomes. The biological causes underlying SOI and SCD, as well as the risk for future cognitive impairment, need further investigation.

Association of Midlife Plasma Amyloid-β Levels With Cognitive Impairment in Late Life: The ARIC Neurocognitive Study.

To evaluate the association between midlife plasma amyloid-β (Aβ1-42, Aβ1-40, Aβ42:Aβ40) and risk of mild cognitive impairment (MCI) and dementia. Plasma Aβ42 and Aβ40 were retrospectively measured with a fluorometric bead-based immunoassay in a subsample of the Atherosclerosis Risk in Communities cohort study. We investigated the relationship of plasma Aβ42, Aβ40, and Aβ42:Aβ40 ratio measured in midlife and late life and the change from midlife to late life to risk of MCI, dementia, and combined MCI/dementia outcomes in late life (from 2011-2019). We used multinomial logistic regressions estimating relative risk ratios (RRRs) of these cognitive outcomes vs cognitively normal adjusted for age, sex, education, site-race, APOE, hypertension, diabetes, and body mass index. A total of 2,284 participants were included (midlife mean age 59.2 ± 5.2, 57% female, 22% Black). Each doubling of midlife Aβ42:Aβ40 was associated with 37% lower risk of MCI/dementia (RRR 0.63, 95% confidence interval [CI] 0.46-0.87), but only up to approximately the median (spline model threshold 0.20). Every 1-SD increase in plasma Aβ42 (10 pg/mL) was associated with 13% lower risk of MCI/dementia (RRR 0.87, 95% CI 0.77-0.98), whereas every 1-SD increase in plasma Aβ40 (67 pg/mL) was associated with 15% higher risk of MCI/dementia (RRR 1.15, 95% CI 1.01-1.29). Associations were comparable but slightly weaker statistically when models were repeated using late-life plasma Aβ predictors. Aβ42 and Aβ40 increased from midlife to late life, but changes were not associated with cognitive outcomes. Midlife measurement of plasma Aβ may have utility as a blood-based biomarker indicative of risk for future cognitive impairment.

Blood Pressure Profiles and Cognitive Function from Adulthood to Old Age: Chasing a Golden Middle Way?

With the demographic shift toward advanced ages, it is imperative to understand the biological mechanisms behind common, disabling age-related diseases such as cognitive impairment in its mild form to overt dementia. Hypertension, a major cardiovascular risk factor, is epidemiologically linked to vascular and Alzheimer-type dementia, with possible mechanisms being atherosclerotic macro- and microvascular damage leading to neuronal cell death, as well as proinflammatory events responsible for neurodegeneration. Nevertheless, there is currently a knowledge gap as to which population to target, what the diagnostics test, and how to manage early pathogenic events in order to prevent such a dramatic and disabling condition. While clinical trials data support the benefit of active BP control with antihypertensive medications on the risk of future cognitive impairment, hypotension appears to be related to accelerated cognitive decline in both the fit and the cognitively frail elderly. Dedicated, technologically advanced studies assessing the relation of BP with dementia are needed to clarify the pathophysiological mechanisms in the association before a tailored preventive, diagnostic, and therapeutic approach to one of the most widespread modern medical challenges becomes a reality.

Carotenoids and Cognitive Outcomes: A Meta-Analysis of Randomized Intervention Trials.

Recent evidence suggests that diet can modify the risk of future cognitive impairment and dementia. A biologically plausible rationale and initial clinical data indicate that the antioxidant activities of dietary carotenoids may assist the preservation of cognitive function. A meta-analysis of randomized controlled trials was conducted to examine the relationship between carotenoid supplementation and cognitive performance. A literature search was conducted in the MEDLINE (via PubMed), Scopus, Web of Science, and Cochrane databases from their inception to July 2020. A total of 435 studies were retrieved. screening using predefined inclusion and exclusion criteria was followed by full-text screening and data extraction of study characteristics and measured outcomes. A meta-analysis of eligible trials was performed using a random-effects model to estimate pooled effect size. We identified 9 studies with a total of 4402 nondemented subjects, whose age ranged from 45 to 78 years. Results of the pooled meta-analysis found a significant effect of carotenoid intervention on cognitive outcomes (Hedge’s g = 0.14; 95% confidence interval: 0.08, 0.20, p < 0.0001). There was no evidence of heterogeneity among the studies (τ2 = 0.00, I2 = 0.00%, H2 = 1.00) or publication bias. Although further studies are needed, our results suggest that carotenoid interventions are associated with better cognitive performance. Thus, these dietary compounds may help to reduce the risk of cognitive impairment and dementia.

White Matter Hyperintensities Mediate Impact of Dysautonomia on Cognition in Parkinson's Disease.

Patients with Parkinson's disease (PD) present with a broad spectrum of nonmotor features including autonomic disorders. More severe autonomic dysfunction in PD is associated with increased cognitive deficits. The presence of cerebral small-vessel disease, measured by T2-weighted magnetic resonance imaging white matter hyperintensity (WMH) burden, is also observed in patients with PD with faster cognitive decline. To investigate whether baseline orthostatic hypotension and autonomic dysfunction in early-stage PD affect later cognitive decline via mediation through cerebral small-vessel disease. De novo PD patients (N = 365) and age-matched controls (N = 174) with baseline T2-weighted/ fluid-attenuated inversion recovery scans were selected from the Parkinson's Progression Markers Initiative. WMHs were automatically segmented. Mediation analysis was used to assess whether WMH load mediates the effect of orthostatic hypotension and autonomic dysfunction (measured by Scales for Outcomes in Parkinson's Disease-Autonomic) on future cognitive decline (measured by Montreal Cognitive Assessment) in an average of 4 years of follow-up. Mediation analysis supported the existence of a full mediation of WMHs on the effect of diastolic orthostatic hypotension in patients with PD and future cognitive decline (average causal mediation effect: ab = -0.032, 95% confidence interval = -0.064 to -0.01, P = 0.01). There was also a partial mediation for overall autonomic dysfunction (ab = -0.027, 95% confidence interval = -0.054 to 0.00, P = 0.02). WMHs fully mediate the effect of diastolic orthostatic hypotension and partially mediate the effect of autonomic dysregulation on future cognitive decline in patients with PD. Our findings support the hypothesis that autonomic dysfunction in early clinical stages predisposes the brain to WMHs through dysregulation of the blood flow in the small vessels. This in turn increases the risk of future cognitive impairment in early PD.

Protocol of Aerobic Exercise and Cognitive Health (REACH): A Pilot Study.

A growing body of evidence supports that aerobic exercise can decrease the risk of future cognitive impairment and Alzheimer’s disease (AD). There is a pressing need to rigorously determine whether cognitively normal yet at-risk individuals stand to benefit from the protective effects of exercise. The present study will test the feasibility of an aerobic exercise intervention in such a population and inform the design of a larger-scale randomized, controlled trial examining the effect of aerobic exercise on biomarkers of AD in late-middle-aged, at-risk individuals. This was a single-site, 1 : 1 block-randomized, parallel, two-arm trial. Cognitively normal participants aged 45–80 with documentation of familial and genetic AD risk factors were randomly assigned to one of two interventions. The Usual Physical Activity group was provided educational materials about exercise. The Enhanced Physical Activity intervention delivered 26 weeks of individualized and supervised aerobic exercise. Exercise duration and intensity were incrementally increased to 150 min/week and 70–80% of heart rate reserve, respectively. Retention and adherence were measured to assess study feasibility. In addition, pre- and post- intervention differences between the two arms were evaluated for cardiorespiratory fitness, physical activity, brain glucose metabolism, cerebral structure, vascular health, memory, executive function, and mood. Data from randomized controlled trials of exercise training are needed to identify the proper exercise prescription for reducing accumulation of AD biomarkers in cognitively normal individuals. The current trial will contribute to filling that gap while informing the design of large-scale trials.

MILD BEHAVIORAL IMPAIRMENT AS A PREDICTOR OF COGNITIVE FUNCTIONING IN OLDER ADULTS

Mild behavioral impairment (MBI) was coined to describe individuals who have neuropsychiatric symptoms before they meet clinical criteria for mild cognitive impairment or dementia. Individuals with MBI are found to be at greater risk of dementia compared to those without these symptoms, therefore identifying how MBI might relate to different domains of cognition is of key importance, as it may help us to identify which individuals are at even greater risk for future cognitive impairment. Secondary data analysis of a sample (n=291) of cognitively healthy older adults from the Florida Alzheimer's Disease Research Center who are presenting with MBI, as defined by decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, or abnormal perception or thought content. Cognitive abilities, specifically executive function, attention, short-term memory, and episodic memory, were compared using a battery of neuropsychological assessments. Individuals with MBI performed significantly worse on tasks associated with attention. Significant differences on tasks of attention were also found for only individuals who had decreased motivation or affective dysregulation. Persons with decreased motivation were found to perform worse on tasks associated with executive function and short-term memory, where individuals with affective dysregulation were found to perform worse on tasks of short-term memory. Finally, those with social inappropriateness performed worse on a task associated with episodic memory. The present study found evidence that cognitively healthy individuals with MBI are more likely to experience greater changes in attention compared to individuals without MBI. Further, decreased motivation and affective dysregulation is associated with worse performance on multiple domains of cognition, where social inappropriateness was found to only be associated with worse performance in one domain, and impulse dyscontrol and abnormal perception or thought content was found to be associated with none.

Reverters from PD-MCI to cognitively intact are at risk for future cognitive impairment: Analysis of the PPMI cohort

IntroductionPast studies have shown that a large portion of individuals with Parkinson's disease (PD) and mild cognitive impairment (MCI) will revert to a cognitively intact (CI) status in the future. Aging studies have shown that individuals who revert from MCI to CI are at increased risk for reconverting to MCI or dementia in the future. The current study examined if individuals who revert from PD-mild cognitive impairment (PD-MCI) to CI will be at increased risk for future PD-MCI and Parkinson's disease dementia (PDD). MethodThe study utilized data from the Parkinson's Progression Markers Initiative (PPMI). The sample included 364 newly diagnosed PD participants who were followed annually for up to 4 years. Based on the first and second assessments, we identified individuals who were CI at each assessment (CI-Stable) and individuals who were PD-MCI at baseline but then reverted to CI (Reversion). Analyses examined if participants in the Reversion group were at greater risk, relative to the CI-Stable group, for cognitive impairment at future assessments. ResultsParticipants in the Reversion group were at greater risk for future cognitive impairment (PD-MCI or PDD) at the 2nd, 3rd and 4th annual follow-up, relative to the CI-Stable group. The Reversion group continued to be at increased risk for future cognitive impairment when adjusting for age, gender, education, depressive symptoms, and motor severity. ConclusionA large proportion of individuals with PD-MCI will not show evidence of cognitive impairment within a year. However, these “reverters” continue to be at risk for future development of cognitive impairment.

Age-Related Eye Disease and Participation in Cognitive Activities

Studies have found a benefit to living a cognitively active life in older age. Our goal was to quantify participation in cognitively stimulating activities in adults with and without age-related eye disease. We conducted a cross-sectional hospital-based study in Montreal, Canada of older adults (n = 303) having either age-related macular degeneration (AMD) (n = 96), glaucoma (n = 93), or normal vision (n = 114). To be eligible, the AMD group had to have bilateral late stage AMD with a better eye visual acuity of 20/30 or worse. The glaucoma group had to have a diagnosis of bilateral primary open-angle glaucoma with visual field mean deviation < = −4 dB in their better eye. Further inclusion criteria included age ≥ 65 and a Mini-Mental State Exam Blind score ≥ 10. Cognitive activities were measured using the Victoria Longitudinal Study Activity Questionnaire. Linear regression was used. Patients with AMD (β = −4.2, 95% confidence interval (CI) −6.0, −2.4) and glaucoma (β = −1.8, 95% CI −3.3, −0.3) participated in fewer cognitive activities per month compared to those with normal vision after adjusting for age, sex, education, diabetes, number of comorbidities, cognition, and cataract. People with AMD and glaucoma participated in fewer cognitive activities, which could put them at risk for future cognitive impairment.

Multivariate analyses of peripheral blood leukocyte transcripts distinguish Alzheimer's, Parkinson's, control, and those at risk for developing Alzheimer's

The need for a reliable, simple, and inexpensive blood test for Alzheimer's disease (AD) suitable for use in a primary care setting is widely recognized. This has led to a large number of publications describing blood tests for AD, which have, for the most part, not been replicable. We have chosen to examine transcripts expressed by the cellular, leukocyte compartment of blood. We have used hypothesis-based cDNA arrays and quantitative PCR to quantify the expression of selected sets of genes followed by multivariate analyses in multiple independent samples. Rather than a single study with no replicates, we chose an experimental design in which there were multiple replicates using different platforms and different sample populations. We have divided 177 blood samples and 27 brain samples into multiple replicates to demonstrate the ability to distinguish early clinical AD (Clinical Dementia Rating scale 0.5), Parkinson's disease (PD), and cognitively unimpaired APOE4 homozygotes, as well as to determine persons at risk for future cognitive impairment with significant accuracy. We assess our methods in a training/test set and also show that the variables we use distinguish AD, PD, and control brain. Importantly, we describe the variability of the weights assigned to individual transcripts in multivariate analyses in repeated studies and suggest that the variability we describe may be the cause of inability to repeat many earlier studies. Our data constitute a proof of principle that multivariate analysis of the transcriptome related to cell stress and inflammation of peripheral blood leukocytes has significant potential as a minimally invasive and inexpensive diagnostic tool for diagnosis and early detection of risk for AD.

Kidney-brain axis inflammatory cross-talk: from bench to bedside.

Epidemiologic data suggest that individuals at all stages of chronic kidney disease (CKD) have a higher risk of developing neuropsychiatric disorders, cognitive impairment, and dementia. This risk is generally explained by the high prevalence of both symptomatic and subclinical ischemic cerebrovascular lesions. However, other potential mechanisms, including cytokine/chemokine release, production of reactive oxygen species (ROS), circulating and local formation of trophic factors and of renin-angiotensin system (RAS) molecules, could also be involved, especially in the absence of obvious cerebrovascular disease. In this review, we discuss experimental and clinical evidence for the role of these mechanisms in kidney-brain cross-talk. In addition, we hypothesize potential pathways for the interactions between kidney and brain and their pathophysiological role in neuropsychiatric and cognitive changes found in patients with CKD. Understanding the pathophysiologic interactions between renal impairment and brain function is important in order to minimize the risk for future cognitive impairment and to develop new strategies for innovative pharmacological treatment.

Risk Factors for Mild Cognitive Impairment, Dementia and Mortality: The Sydney Memory and Ageing Study

BackgroundThe nature and commonality of late-life risk factors for mild cognitive impairment (MCI), dementia, and mortality remain unclear. Our aim was to investigate potential risk factors, simultaneously in a single cohort including many individuals initially with normal cognition and followed for 6 years. MethodsWe classified 873 community-dwelling individuals (70–90 years old and without dementia at baseline) from the Sydney Memory and Ageing Study as cognitively normal (CN), having MCI or dementia, or deceased 6 years after baseline. Associations with baseline demographic, lifestyle, health, and medical factors were investigated, including apolipoprotein (APOE) genotype, MCI at baseline, and reversion from MCI to CN within 2 years of baseline. ResultsEighty-three (9.5%) participants developed dementia and 114 (13%) died within 6 years; nearly 33% had MCI at baseline, of whom 28% reverted to CN within 2 years. A core set of baseline factors was associated with MCI and dementia at 6 years, including older age (per year: odds ratios and 95% confidence intervals = 1.08, 1.01–1.14 for MCI; 1.19, 1.09–1.31 for dementia), MCI at baseline (5.75, 3.49–9.49; 8.23, 3.93–17.22), poorer smelling ability (per extra test point: 0.89, 0.79–1.02; 0.80, 0.68–0.94), slower walking speed (per second: 1.12, 1.00–1.25; 1.21, 1.05–1.39), and being an APOE ε4 carrier (1.84, 1.07–3.14; 3.63, 1.68–7.82). All except APOE genotype were also associated with mortality (age: 1.11, 1.03–1.20; MCI: 3.87, 1.97–7.59; smelling ability: 0.83, 0.70–0.97; walking speed: 1.18, 1.03–1.34). Compared with stable CN participants, individuals reverting from MCI to CN after 2 years were at greater risk of future MCI (3.06, 1.63–5.72). Those who reverted exhibited some different associations between baseline risk factors and 6-year outcomes than individuals with stable MCI. ConclusionA core group of late-life risk factors indicative of physical and mental frailty are associated with each of dementia, MCI, and mortality after 6 years. Tests for slower walking speed and poorer smelling ability may help screen for cognitive decline. Individuals with normal cognition are at greater risk of future cognitive impairment if they have a history of MCI.