Greater Risk Of Cognitive Decline Research Articles

Sensorimotor and Frontoparietal Network Connectivity Are Associated With Subsequent Maintenance of Gait Speed and Episodic Memory in Older Adults.

Slow gait is predictive of functional impairments in older adults, while concomitant slow gait and cognitive complaints are associated with a greater risk for cognitive decline and dementia. However, functional neural correlates for gait speed maintenance are unclear. As the sensorimotor network (SMN) and frontoparietal network (FPN) are integral components of these functions, this study investigated differences in SMN and FPN in older adults with/without gait speed decline over 24 months; and whether these networks were associated with the maintenance of cognitive function. We included 42 community-dwelling older adults aged >70 years from the MOBILIZE Boston Study. Resting-state fMRI was performed at the study baseline. Participant characteristics, gait speed, Mini-Mental State Examination, and Hopkins Verbal Learning Test (HVLT) were assessed at baseline and at 24-month follow-up. Decliners were identified as individuals with >0.05 meters/second decline in gait speed from baseline to 24 months. Of the 26 decliners and 16 maintainers, decliners exhibited a significant decline in delayed-recall performance on the HVLT over 24 months. Controlling for baseline age and multiple comparisons, contrary to initial hypothesis, maintainers exhibited lower baseline primary motor and premotor connectivity (p = .01) within the SMN, and greater baseline ventral visual-supramarginal gyrus connectivity within the FPN (p = .02) compared to decliners. Lower primary motor-premotor connectivity was correlated with maintenance of delayed-recall performance on the HVLT (p = .04). These findings demonstrated a potential compensatory mechanism involved in the link between the decline in gait speed and episodic memory, whereby baseline connectivity of the SMN and FPN may underlie subsequent maintenance of gait speed and cognitive function in old age.

Depression interacts with allostatic load to predict cognitive decline in middle age

BackgroundAllostatic load (AL) indicates the cumulative impact of stress on homeostatic mechanisms. Depression and AL have been associated with cognitive deficits, but it is unclear if they do so independently. MethodsUsing data from middle-aged participants in the observational longitudinal Midlife in the United States (MIDUS) study (n = 704, 57.5 % female, 63.8 ± 10.6 years old in 2014), we assessed whether the effect of prior depression (Composite International Diagnostic Interview Short-Form in 1995) on cognitive decline between 2004 and 2013 (composite Z-scores derived from the Brief Test of Adult Cognition by Telephone and the Stop & Go Switch Task) was moderated by AL Z-scores in 2004 (calculated from biomarkers in blood, urine, and electrocardiography). ResultsA significant depression × AL interaction predicted a decline in a composite cognitive score (β = −0.066, SE=0.029, p = 0.024) and executive function (β = −0.068, SE=0.025, p = 0.007). Depression predicted a decline in composite cognition among those with AL Z-scores above − 0.055. AL subdomains of inflammation and lipid metabolism showed evidence of moderation. ConclusionMiddle-aged adults with depression who had higher allostatic load were at greater risk of cognitive decline. Future studies should evaluate whether the interaction predicts incident dementia, and whether interventions targeting depression or elevated AL in people who have both can attenuate cognitive decline.

Contributions of sex and genotype to exploratory behavior differences in an aged humanized APOE mouse model of late-onset Alzheimer's disease.

Age, genetics, and chromosomal sex have been identified as critical risk factors for late-onset Alzheimer's disease (LOAD). The predominant genetic risk factor for LOAD is the apolipoprotein E ε4 allele (APOE4), and the prevalence of LOAD is higher in females. However, the translational validity of APOE4 mouse models for AD-related cognitive impairment remains to be fully determined. The present study investigated the role of both sex and genotype on learning and memory in aged, humanized APOE knock-in mice. Aged (23.27 mo ± 1.21 mo; 39 male/37 female) APOE3/3, APOE3/4, and APOE4/4 mice performed a novel object recognition (NOR) assay. Task-related metrics were analyzed using two-way sex by genotype ANOVAs. Sex differences were more prominent relative to APOE genotype. Prior to NOR, female mice exhibited thigmotaxic center zone avoidance during the open field task relative to males, regardless of genotype. Within object familiarization and NOR tasks, females had greater object interaction and locomotion. Interestingly, only APOE4/4 females on average recognized the novel object. These results suggest that APOE4, although strongly related to LOAD pathogenesis, does not drive cognitive decline in the absence of other risk factors even in very aged mice. Chromosomal sex is a key driver of behavioral phenotypes and thus is a critical variable for translatability of interventions designed to preserve learning and memory in animal models of LOAD. Last, there was a very high degree of variability in behavioral performance across APOE genotypes. A cluster analysis of the behavioral data revealed a low-activity and a high-activity cluster. APOE4 carriers were overrepresented in the low-activity cluster, while male:female distributions did not differ. Collectively, the behavioral data indicate that chromosomal sex has the greatest impact on behavioral phenotype, and APOE4 carrier status may confer greater risk for cognitive decline in some animals.

Multisensory integration precision is associated with better cognitive performance over time in older adults: A large-scale exploratory study.

Age-related sensory decline impacts cognitive performance and exposes individuals to a greater risk of cognitive decline. Integration across the senses also changes with age, yet the link between multisensory perception and cognitive ageing is poorly understood. We explored the relationship between multisensory integration and cognitive function in 2875 adults aged 50 + from The Irish Longitudinal Study on Ageing. Multisensory integration was assessed at several audio-visual temporal asynchronies using the Sound Induced Flash Illusion (SIFI). More precise integration (i.e. less illusion susceptibility with larger temporal asynchronies) was cross-sectionally associated with faster Choice Response Times and Colour Trail Task performance, and fewer errors on the Sustained Attention to Response Task. We then used k-means clustering to identify groups with different 10-year cognitive trajectories on measures available longitudinally; delayed recall, immediate recall and verbal fluency. Across measures, groups with consistently higher performance trajectories had more precise multisensory integration. These findings support broad links between multisensory integration and several cognitive measures, including processing speed, attention and memory, rather than association with any specific subdomain.

Impact of APOE and BDNF Val66Met polymorphisms on spatial navigation and brain morphometry in subjective cognitive decline

AbstractBackgroundThe apolipoprotein E (APOE) ɛ4 allele is associated with episodic memory deficits, less accurate spatial navigation and hippocampal atrophy in nondemented older adults. The brain‐derived neurotrophic factor (BDNF) Met allele may further worsen memory impairment and reduce hippocampal activation in APOE ɛ4 carriers but its role in APOE ɛ4‐related spatial navigation deficits has not been established. We aimed to evaluate the influence of combination of the APOE and BDNF Val66Met polymorphisms on spatial navigation, cognitive functions and volumes of selected brain regions associated with spatial navigation including the hippocampus, entorhinal cortex, precuneus, inferior parietal and posterior cingulate cortex in individuals with subjective cognitive decline (SCD).MethodIn total, 71 older adults with SCD from the Czech Brain Aging Study were stratified based on the APOE and BDNF Val66Met polymorphisms into four groups: ɛ4–/BDNF Val/Val (n =27), ɛ4–/BDNF Met (n = 15), ɛ4+/BDNF Val/Val (n =18), and ɛ4+/BDNF Met (n=11). The participants underwent comprehensive neuropsychological examination, brain MRI and spatial navigation testing of egocentric, allocentric, and allocentric delayed navigation in a real‐space human analogue of the Morris water maze.ResultThe ɛ4+/BDNF Met group, although similar to other polymorphism groups in age, gender, education, depressive symptoms and global cognitive function, had less accurate allocentric and allocentric delayed navigation performance than the ɛ4–/BDNFVal/Val group (p<0.05). There were no significant differences in egocentric navigation performance, cognitive performance in any cognitive domain including attention and working memory, nonverbal memory, executive function, language and visuospatial function and volumes of selected brain regions associated with spatial navigation between the polymorphism groups (p>0.05).ConclusionIndividuals with SCD and the high risk combination of APOE ɛ4 and BDNF Met alleles had less accurate allocentric spatial navigation than those with the low risk combination of APOE ɛ3 and BDNF Val alleles. This finding may indicate that individuals with SCD and two high risk gene polymorphisms are particularly susceptible to hippocampus‐dependent spatial navigation deficits and may be at greater risk of cognitive decline and progression to mild cognitive impairment. Our results also suggest that spatial navigation testing could more reliably assess the deleterious effect of the BDNF Met allele on cognition than other cognitive tests.

No effect of exercise on AD‐related cognition in older African Americans: Program for African American Cognition and Exercise (PAACE)

AbstractBackgroundLower levels of physical activity (PA) are associated with greater risk of cognitive decline and AD, and some studies suggest that interventions that increase PA engagement lower risk of cognitive decline and AD. However, interventions to date have largely not included substantial representation of African Americans.MethodThe Program for African American Cognition and Exercise (PAACE) randomized 56 sedentary African American adults in the Baton Rouge, Louisiana area (mean age ± s.d.: 69.2 ± 3.4 years) to a physical activity group (PAG) or successful aging group (SAG). The PAG aimed to increase moderate to vigorous PA to national guideline levels over 12 weeks by providing supervised PA 2 days per week (90‐120 minutes/week) at local YMCAs along with 30‐60 minutes/week of home‐based PA. The SAG completed one 60‐minute educational session on successful aging per week for 12 weeks. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was assessed before and after the intervention. ANOVA models assessed pre‐ to post‐intervention RBANS total scale and sub‐scale score changes, as well as differences between PA and control arms in these changes.ResultGroups were well matched by age, sex, BMI, employment, education, and income. The SAG increased scores on the RBANS overall scale and scales of visuospatial function, immediate memory, and delayed memory, along with the story memory, figure copying, coding, and figure recall sub‐scales (all p<.05). The PAG increased scores on only the list learning sub‐scale (p=.047). Scores on the overall scale (p=.034) and story memory sub‐scale (p=.0008) increased significantly more in the SAG than in the PAG. No RBANS scores increased significantly more in the PAG compared to the SAG.ConclusionA 12‐week PA promotion program among community‐dwelling older African American adults provided significant cognitive benefits to an educational control group, and minimal benefits to those engaged in PA. Possible contributors to these results include inadequate PA stimulus in the PAG, and beneficial health behavior changes or cognitive stimulation in the SAG. Future research is needed to fully understand cognitive effects of PA interventions among older African Americans.

Sex differences in predictors for cognitive decline and dementia in people with stroke or transient ischemic attack in the PROGRESS trial.

Stroke and transient ischemic attack confer greater risk of cognitive decline and dementia. We used data from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a blood pressure-lowering randomized controlled trial in stroke/transient ischemic attack. We evaluated overall and sex-specific differences in treatment effects for cognitive decline/dementia, as well as associations with vascular and stroke-specific predictors,considering death as a competing risk. Multinomial logistic regression was used to estimate overall and sex-specific odds ratios (OR) (95% confidence intervals (CI)) for treatment effects and predictors associated with the risk of cognitive decline/dementia, and the women-to-men ratio of odds ratio (RORs). Over a median four years, 763 cognitive decline/dementia (30.9% women) were recorded in 5888 participants. Women had lower odds of cognitive decline/dementia than men (OR 0.78, 95%CI 0.63-0.95). Active treatment was associated with lower odds of cognitive decline/dementia (0.84, 0.72-0.98), with no evidence of sex difference. Higher education (0.96,0.94-0.98 (per year)) and baseline Mini-Mental State Examination (MMSE)) were associated with lower odds of cognitive decline/dementia (0.84,0.82-0.86 (per point higher)). Higher diastolic blood pressure (1.11,1.02-1.20 (per 10 mmHg)), low estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (1.27,1.03-1.58), and peripheral arterial disease (1.78,1.26-2.52) were associated with higher odds of cognitive decline/dementia. APOE ɛ4 was not associated with cognitive decline/dementia (1.05 (0.85-1.30)). Low eGFR was more strongly associated with cognitive decline/dementia in women than men (RORs, 1.60 (1.03-2.48)). Diabetes was more strongly associated with men than women. Several risk factors were associated with cognitive decline/dementia in people with prior stroke/transient ischemic attack, with notable sex differences. Long-term cognitive sequelae of stroke should be considered to strengthen joint prevention strategies for stroke, cognitive decline, and dementia.Trial Registration: This trial was not registered because enrolment began before 1 July 2005.

Intrusion errors moderate the relationship between blood glucose and regional cerebral blood flow in cognitively unimpaired older adults

Regional cerebral blood flow (CBF) has a complex relationship with cognitive functioning such that cognitively unimpaired individuals at risk for Alzheimer’s disease (AD) may show regional hyperperfusion, while those with cognitive impairment typically show hypoperfusion. Diabetes and word-list intrusion errors are both linked to greater risk of cognitive decline and dementia. Our study examined associations between fasting blood glucose, word-list intrusion errors, and regional CBF. 113 cognitively unimpaired older adults had arterial spin labeling MRI to measure CBF in a priori AD vulnerable regions: medial temporal lobe (MTL), inferior parietal lobe (IPL), precuneus, medial orbitofrontal cortex (mOFC), and pericalcarine (control region). Hierarchical linear regressions, adjusting for demographics, vascular risk, and reference CBF region, examined the main effect of blood glucose on regional CBF as well as whether intrusions moderated this relationship. Higher glucose was associated with higher CBF in the precuneus (β = .134, 95% CI = .007 to .261, p = .039), IPL (β = .173, 95% CI = .072 to .276, p = .001), and mOFC (β = .182, 95% CI = .047 to .320, p = .009). There was no main effect of intrusions on CBF across regions. However, the glucose x intrusions interaction was significant such that having higher glucose levels and more intrusion errors was associated with reduced CBF in the MTL (β = -.186, 95% CI = -.334 to -.040, p = .013) and precuneus (β = -.146, 95% CI = -.273 to -.022, p = .022). These findings may reflect early neurovascular dysregulation, whereby higher CBF is needed to maintain unimpaired cognition in individuals with higher glucose levels. However, lower regional CBF in unimpaired participants with both higher glucose and more intrusions suggests a failure in this early compensatory mechanism that may signal a decrease in neural activity in AD vulnerable regions.

Increased reporting of subjective cognitive complaints over time predicts cognitive decline and incident dementia.

Subjective cognitive complaints (SCCs) are a risk factor for dementia; however, little is known about their trajectories. Participants were 873 older adults (mage=78.65 years; 55% females) from the Sydney Memory and Ageing Study that were followed-up biennially. SCCs were measured using the six-item Memory Complaint Questionnaire. Associations between initial level of SCC reporting, linear change in SCC reporting, and change in global cognition over 6years was examined using latent growth curve analysis. Risk of dementia was examined over 10years using Cox regression. After controlling for demographics, mood and personality, results revealed a negative longitudinal association between the slope of SCCs and the slope of global cognition scores (b=-0.01, p=0.005, β=-0.44), such that participants who reported increasing SCCs showed a steeper rate of decline in global cognition over 6years. Cox regression also revealed participants who reported increasing SCCs had a nearly fourfold increased risk of developing dementia over 10years (hazard ratio 3.70, 1.24-11.01). This study explored whether initial levels of, and change in, SCCs over time are associated with both cognitive decline and risk of dementia. These findings are clinically relevant as GPs should note patients reporting increasing SCCs as they may be at greater risk of cognitive decline and incident dementia.

Association of Chemotherapy, Enzalutamide, Abiraterone, and Radium 223 With Cognitive Function in Older Men With Metastatic Castration-Resistant Prostate Cancer

Older adults are at greater risk of cognitive decline with various oncologic therapies. Some commonly used therapies for advanced prostate cancer, such as enzalutamide, have been linked to cognitive impairment, but published data are scarce, come from single-group studies, or focus on self-reported cognition. To longitudinally examine the association between cognitive function and docetaxel (chemotherapy), abiraterone, enzalutamide, and radium Ra 223 dichloride (radium 223) in older men with metastatic castration-resistant prostate cancer. A multicenter, prospective, observational cohort study was conducted across 4 academic cancer centers in Ontario, Canada. A consecutive sample of 155 men age 65 years or older with metastatic castration-resistant prostate cancer starting any treatment with docetaxel, abiraterone acetate, enzalutamide, or radium Ra 223 dichloride (radium 223) were enrolled between July 1, 2015, and December 31, 2019. First-line chemotherapy (docetaxel), abiraterone, enzalutamide, or radium 223. Cognitive function was measured at baseline and end of treatment using the Montreal Cognitive Assessment, the Trail Making Test part A, and the Trail Making Test part B to assess global cognition, attention, and executive function, respectively. Absolute changes in scores over time were analyzed using univariate and multivariable linear regression, and the percentages of individuals with a decline of 1.5 SDs in each domain were calculated. A total of 155 men starting treatment with docetaxel (n = 51) (mean [SD] age, 73.5 [6.2] years; 34 [66.7%] with some postsecondary education), abiraterone (n = 29) (mean [SD] age, 76.2 [7.2] years; 18 [62.1%] with some postsecondary education), enzalutamide (n = 54) (mean [SD] age, 75.7 [7.4] years; 33 [61.1%] with some postsecondary education), and radium 223 (n = 21) (mean [SD] age, 76.4 [7.2] years; 17 [81.0%] with some postsecondary education) were included. Most patients had stable cognition or slight improvements during treatment. A cognitive decline of 1.5 SDs or more was observed in 0% to 6.5% of patients on each measure of cognitive function (eg, 3 of 46 patients [6.5%; 95% CI, 2.2%-17.5%] in the group receiving chemotherapy [docetaxel] had a decline of 1.5 SDs for Trails A and Trails B). Although patients taking enzalutamide had numerically larger declines than those taking abiraterone, differences were small and clinically unimportant. These findings suggest that most older men do not experience significant cognitive decline in attention, executive function, and global cognition while undergoing treatment for advanced prostate cancer regardless of the treatment used.

The Relationship Between Cardiorespiratory Fitness and Middle Cerebral Artery Velocity in Women

Age-related declines in cerebral blood flow have been linked to greater risk for cognitive decline. Habitual exercise is recommended to prevent or delay cognitive impairment. Previous studies have found a positive correlation between cardiorespiratory fitness and middle cerebral artery blood velocity (MCAv) in men; however, there is limited data on this relationship in women. This study aimed to examine the relationships between cardiorespiratory fitness, age and MCAv in women. We hypothesized that MCAv would decline with advancing age and there would be a positive association between MCAv and cardiorespiratory fitness in women. Data from 74 women (age = 46 ± 21 y, range = 18 – 83 yrs.) were collected at 4 institutions (University of Kansas Medical Center; University of Wisconsin-Madison; Université Laval; Mayo Clinic) as part of previously conducted studies. All participants were determined to be of low risk for cardiovascular disease according to the American College of Sports Medicine criteria. MCAv, mean arterial pressure, end tidal carbon dioxide and cardiorespiratory fitness (maximal oxygen consumption: VO2max) were retrieved from study records. MCAv was collected unilaterally at rest using a transcranial Doppler ultrasound. VO2max was collected during either cycling ergometry (n = 61) or treadmill ergometry (n = 13) tests. Associations were assessed using a Pearson product-moment correlation. In the 74 women, the absolute VO2max was 2089 ± 622 ml·min-1 and average relative VO2max was 34 ± 10 ml·kg-1·min-1. The average MCAv for the entire group was 64 ± 16 cm·s-1. As expected, there was an inverse association between age and MCAv (r = -0.310; p = 0.007) such that women who were older demonstrated lower MCAv. There was a positive association between absolute VO2max and MCAv (r = 0.310; p = 0.007). Likewise, there was a positive association between relative VO2max and MCAv (r = 0.309; p = 0.007) such that women with higher cardiorespiratory fitness demonstrated higher MCAv. However, the relationship between VO2max and MCAv was no longer significant when adjusted for age (absolute VO2max; r = -0.105, p = 0.375; relative VO2 max; r = -0.089, p = 0.452). Cardiorespiratory fitness is positively associated with MCAv in women. This suggests that habitual exercise may be protective against age-related declines in cerebral blood flow. However, because the association between cardiorespiratory fitness and MCAv is attenuated when it is adjusted for age, future studies could utilize non-linear modeling to understand how age, MCAv and cardiorespiratory fitness are related in women.

Spousal Loss and Cognitive Functioning: Do Pre-Loss Marital Quality and Gender Matter?

Prior research has found that the risk of cognitive decline increases after the death of a spouse. In general, the impact of life transitions is contingent on contextual factors such as socio-demographic characteristics or relationship quality. However, there is limited research on how marital quality before spousal loss and gender influence the association between spousal loss and cognitive change. The current study examines the effects of spousal loss on change in cognitive functioning as well as the moderating effects of pre-loss marital quality and gender. Data from two waves of the Midlife in the United States (MIDUS) study were analyzed (MIDUS2: 2004-05, MIDUS3: 2013-14). The analytic sample consists of two groups: (1) 179 bereaved adults who were age 54 or older at MIDUS2 (M = 65.2, SD = 9.5) and whose spouses died between MIDUS2 and MIDUS3, and (2) 179 non-bereaved adults, matched with the bereaved group on age and gender, who did not experience spousal loss between the two waves. Cognitive function was assessed via BTACT (Brief Telephone Adult Cognition Test) at both waves. Regression results show that both pre-loss marital quality and gender significantly moderate the association between spousal loss and change in cognitive functioning. Specifically, relative to their counterparts, men and those who reported better marital relationships prior to spousal death had a greater risk of cognitive decline after a spouse’s death. The findings suggest the significance of pre-loss marital quality and gender for cognitive changes in widowhood and have implications for the development of efficient interventions

Decreasing Social Support Associated With Risk of MCI and Dementia Is Partially Mediated by Hippocampal Volume

Less supportive social relationships are linked to greater risk of cognitive decline in older adulthood. Few studies have examined if declines in social support predict risk of developing Mild Cognitive Impairment (MCI) or dementia and the neurobiological factors that may contribute to these associations. We analyzed data from 926 women in the Women’s Health Initiative Memory Study-MRI (WHIMS-MRI) to examine whether low social support at baseline and declines over an 8-year period predicted subsequent risk of developing MCI/dementia. Social support (Medical Outcomes Study Social Support Scale) was self-reported at the baseline (1994-1998) and closeout (2004-2005) of the parent WHI hormone therapy clinical trial. Annual neuropsychological assessments were conducted in WHIMS (through 2018) to ascertain incident MCI/dementia; structural brain scans were performed in 2005-2006. Structural equation models assessed the association between level and change in social support and risk of incident MCI/dementia and putative mediation of these associations by structural brain variables in women free of MCI/dementia as of the trial closeout, adjusting for demographic, lifestyle, depression, and biomedical covariates. Both low baseline social support (HR=1.24 per 1-SD; p<.05) and declines in support (HR=1.18 per 1-SD; p<.05) predicted incident MCI/dementia risk. Women reporting decreasing social support had significantly lower hippocampal volumes (β=-.070; p<.05) which accounted for ~14% of the total effect of declining support on MCI/dementia risk. We will highlight the implications of these findings for understanding how changes in social support may be linked to risk of MCI/dementia, including potential bidirectional associations of changes in social support and neurobiological health.

Impact of arterial hypertension and its management strategies on cognitive function and dementia: a comprehensive umbrella review.

Cognitive decline and dementia recognize multiple risk factors and pathophysiological mechanisms, often involved simultaneously with complex interactions. Several studies have shown that both arterial hypertension and hypotension are associated with a greater risk of cognitive decline and dementia, but clinical evidence on this point is conflicting. Our aim was to conduct an umbrella review on cognitive function, dementia, and blood pressure, with particular attention to epidemiological, prognostic and therapeutic aspects. We conducted a dedicated literature search on PubMed for systematic reviews and meta-analyses that focused on arterial pressure, hypertension, hypotension and similar conditions, and cognitive function, cognitive decline and dementia. The internal validity of systematic reviews and meta-analyses was formally analyzed using the OQAQ tool. The umbrella review was planned in accordance with current international recommendations and was described as specified by the PRISMA guidelines. Seventeen systematic reviews (including 13 meta-analyses) were included, for a total of 675 clinical studies and over 1 million patients. Hypertension results to be associated with a lower risk of Alzheimer's dementia, greater risk of vascular dementia and greater risk of cognitive decline. Orthostatic hypotension seems to be associated with greater risk of Alzheimer's dementia, vascular dementia and dementia of Parkinson's disease. Therapy with acetylcholinesterase inhibitors produces lower risk of cardiovascular events, greater risk of hypertension and greater risk of bradycardia, while the anti-hypertensive therapy leads to a lower risk of dementia of all types and lower risk of cognitive decline. To date, the evidence on the relationship between blood pressure, cognitive decline and dementia provides somewhat heterogeneous data. Further studies are clearly needed, with explicit inclusion criteria as objective as possible, adequate follow-up and precise characterization of implemented cardiovascular and cognitive treatments.

Impact of arterial hypertension and its management strategies on cognitive function and dementia: a comprehensive umbrella review

Introduction Cognitive decline and dementia recognize multiple risk factors and pathophysiological mechanisms, often involved simultaneously with complex interactions. Several studies have shown that both arterial hypertension and hypotension are associated with a greater risk of cognitive decline and dementia, but clinical evidence on this point is conflicting. Our aim was to conduct an umbrella review on cognitive function, dementia, and blood pressure, with particular attention to epidemiological, prognostic and therapeutic aspects. Evidence acquisition We conducted a dedicated literature search on PubMed for systematic reviews and meta-analyses that focused on arterial pressure, hypertension, hypotension and similar conditions, and cognitive function, cognitive decline and dementia. The internal validity of systematic reviews and meta-analyses was formally analysed using the OQAQ tool. The umbrella review was planned in accordance with current international recommendations and was described as specified by the PRISMA guidelines. Evidence synthesis 17 systematic reviews (including 13 meta-analyses) were included, for a total of 675 clinical studies and over 1 million patients. Hypertension results to be associated with a lower risk of Alzheimer's dementia, greater risk of vascular dementia and greater risk of cognitive decline. Orthostatic hypotension seems to be associated with greater risk of Alzheimer's dementia, vascular dementia and dementia of Parkinson's disease. Therapy with acetylcholinesterase inhibitors produces lower risk of cardiovascular events, greater risk of hypertension and greater risk of bradycardia, while the anti-hypertensive therapy leads to a lower risk of dementia of all types and lower risk of cognitive decline. Conclusions To date, the evidence on the relationship between blood pressure, cognitive decline and dementia provides somewhat heterogeneous data. Further studies are clearly needed, with explicit inclusion criteria as objective as possible, adequate follow-up and precise characterization of implemented cardiovascular and cognitive treatments.

Patterns of change in subjective cognitive complaints are associated with cognitive decline and dementia risk: Findings from the Sydney Memory and Ageing Study

AbstractBackgroundSubjective cognitive complaints (SCCs) are now an established risk factor for dementia, however, little is known about whether changing patterns in SCCs over time are associated with cognitive decline and dementia risk. We examine the trajectory of SCCs over a 6‐year period to determine whether intraindividual patterns of reporting SCCs over time is related to cognitive decline and incident dementia.MethodParticipants were 1037 older adults without dementia (M age = 78.65 years; 55% females) from the Sydney Memory and Ageing Study who were followed‐up biennially. Global cognition was measured using a comprehensive neuropsychological battery, and clinical diagnoses were made by an expert consensus panel. SCCs were obtained as participants’ response to a single question concerning their subjective report of memory decline. Patterns of SCCs over time were modelled by conducting categorical latent growth curve analysis using the logit transformation (Figure 1). We examined the associations between average level of SCC likelihood and change in SCC likelihood, with global cognition over six years using latent growth curve analysis, and with risk of incident dementia over 10 years using Cox regression.ResultIn this community‐dwelling older adult sample, there was an annual 10% increase in the odds of reporting SCCs (Figure 2). After controlling for demographics, depression, and personality, results revealed a negative longitudinal association between the slope of SCCs and the slope of global cognition scores, such that participants with an increasing propensity of reporting SCCs over time also showed a steeper rate of decline in global cognition (Figure 4). Cox regression revealed an association between increased SCCs and incident dementia risk (Table 1). That is, participants with an increasing propensity of reporting SCCs over time are also at greater risk for developing dementia (Figure 5).ConclusionThis is the first study to use latent growth curve analysis to examine patterns of change in SCCs overtime. Traditionally, studies examining SCCs longitudinally categorise people as ‘stable’ versus ‘not stable’, however, important information may be lost this way. Understanding patterns of change in SCC reporting over time has significant potential to identify individuals at greater risk of cognitive decline and incident dementia.

AU‐ARROW (Australia)

AbstractBackgroundThe highly encouraging findings from the Finnish Geriatric Intervention Study (known as FINGER) led to the global initiative for dementia risk reduction known as world‐wide FINGERS (WW FINGERS). As part of the collaboration, our Australian AU‐ARROW trial will follow the general protocol of the FINGER trial, and will also be aligned with the U.S. arm of the study, US‐POINTER, though will have minor cultural and dietary modifications to determine the validity of the intervention in an Australian setting.MethodAU‐ARROW is a randomised, single‐blind 2‐year clinical trial that will recruit 600 participants aged 60‐79 satisfying specific inclusion/exclusion criteria, including normal cognition and one or more cardiovascular risk factors that place them at greater risk of cognitive decline. Participants will be distributed across two sites (a) Macquarie University Health Clinics, Sydney, NSW and (b) Sarich Neuroscience Research Institute, Edith Cowan University, Perth, WA, and will be randomised equally into either the innovative multi‐modal intervention group or the study control group, who will receive general lifestyle advice and annual health check‐ups, without treatment. Multi‐modal intervention consists of aerobic exercise, resistance training and stretching; dietary advice with monitoring to encourage adherence to the MIND diet; cognitive training sessions via the Brain HQ computerised online training system; and medical monitoring and regular health education sessions. Heart rate trackers, diet and exercise log books, and the monitoring of Brain HQ sessions will all help with adherence. Primary outcome measure is improvement in global cognitive score, measured using neurocognitive tests identical to those in the US‐POINTER protocol. Additional neurocognitive tests, physical function improvements, detailed diet monitoring and sleep monitoring will provide added data. The unique extra value of AU‐ARROW trial consists of the testing for Alzheimer’s disease (AD) blood biomarkers in all participants; as well as the AD Aβ amyloid‐specific ligand‐PET imaging, brain MRI and retinal biomarker tests that half of the participants will undergo. These tests will provide comprehensive data which have the ultimate purpose of increasing knowledge of the preclinical stages of AD, and help not only to develop preclinical AD diagnostic tests but also efficacy of AU‐ARROW’s intervention.

The effect of docetaxel, enzalutamide, abiraterone, and radium-223 on cognitive function in older men with metastatic castrate-resistant prostate cancer (mCRPC).

73 Background: Older adults are at greater risk of cognitive decline with various oncologic therapies. Emerging data suggest cognitive effects of various therapies for mCRPC but study populations are highly selected and published data are limited and focus mostly on self-reported cognitive function. We evaluated the effects of treatment with docetaxel chemotherapy (CHEMO), abiraterone (ABI), enzalutamide (ENZA), and radium 223 (Ra223) on cognitive function in older men with mCRPC. Methods: Men age 65+ with mCRPC starting any of the 4 treatments for mCRPC were enrolled in this multicenter prospective cohort study. Three short yet reliable and sensitive measures in older adults were administered at baseline and final visit (6 months with CHEMO and Ra223, mean 14-16 months with ENZA and ABI) using the Montreal Cognitive Assessment (MoCA), Trails A, and Trails B to assess global cognition, attention, and executive function, respectively. Absolute changes in cognitive scores over time were analyzed using multivariable linear regression, and the percentage of individuals with a decline of 1.5 SD in each domain were calculated. Higher scores on MoCA are better but worse for Trails A/B. Results: A total of 51, 26, 49, and 21 men starting CHEMO, ABI, ENZA, and Ra223 with complete data were included. Mean age, education, and baseline cognition were similar between groups (Table). Most patients demonstrated stable cognition or slight reductions. Executive function was the most sensitive of the 3 cognitive domains, and declined by at least 1.5 SD in about one-fifth of each cohort. Although ABI had numerically smaller declines than ENZA, differences were generally small and clinically unimportant. Conclusions: Most older men do not experience significant cognitive decline while on treatment for mCRPC regardless of treatment used.[Table: see text]

Low Diastolic Blood Pressure and Cognitive Decline in Korean Elderly People: The Korean Longitudinal Study on Cognitive Aging and Dementia.

ObjectiveCardiovascular diseases are representative risk factors for the onset of cognitive decline. The purpose of this study was to confirm the relationship between diastolic blood pressure and cognitive function in elderly people in Korea. MethodsData from subjects who were enrolled in the prospective Korean Longitudinal Study on Cognitive Aging and Dementia were used in this study. Data from 701 subjects whose diastolic blood pressure range did not change (≤79 mm Hg or ≥80 mm Hg) over 2 years were analyzed. To analyze the differences in cognitive function between the groups at the 2-year follow-up, an analysis of covariance was performed with covariates, which were significantly different between the two groups, and the baseline cognitive function. ResultsSignificant differences were observed between the two groups, and the mean scores on the constructional praxis (η2=0.010) and word list recall tests (η2=0.018) in the diastolic blood pressure ≥80 mm Hg group were higher than those in the diastolic blood pressure ≤79 mm Hg group at the 2-year follow-up. ConclusionThese results indicate that maintaining a DBP below 79 mm Hg presents a greater risk of cognitive decline in Korean elderly people.

A randomized placebo-controlled trial of using B vitamins to prevent cognitive decline in older mild cognitive impairment patients.

Mild cognitive impairment (MCI) patients are at risk of cognitive decline, while elevated serum homocysteine is also associated with cognitive impairment. Thus, older people with MCI and hyperhomocysteinemia may be under greater risk of cognitive decline. We therefore performed a randomized trial of homocysteine-lowering by B vitamins supplementation to prevent cognitive decline in older MCI patients with elevated serum homocysteine. 279 MCI outpatients aged ≥65 years with serum homocysteine ≥10.0μmol/L were randomly assigned to take either methylcobalamin 500μg and folic acid 400μg once daily, or two placebo tablets for 24 months. All subjects were followed up at 12 monthly intervals. The primary outcome was cognitive decline as defined by an increase in clinical dementia rating scale (CDR) sum of boxes (CDR_SOB). The secondary outcomes were global CDR, memory Z score, executive function Z score and Hamilton depression rating scale (HDRS) score. The clinical characteristics between two groups were well matched, except that the supplement group had better executive function. The supplement effectively lowered serum homocysteine (mean 13.9±sd 3.5μmolat baseline to 9.3±2.4μmol/L at month 24). At month 24, there was no significant group difference in CDR_SOB or any secondary outcomes (mean changes in CDR_SOB 0.36 versus 0.22 in supplement and placebo groups respectively). At month 12, the supplement group significantly improved in executive function and had lower HDRS score (P=0.004 and 0.012 respectively). Group difference was significant for HDRS, but borderline significant for executive function. (P=0.01; 0.06 respectively) These effects were not significant at month 24. Subgroup analysis showed that aspirin use had significant interaction with B supplements in CDR_SOB at month 24 (Beta 0.189, P=0.005). Vitamin B12 and folic acid supplementation did not reduce cognitive decline in older people with MCI and elevated serum homocysteine, though the cognitive decline over two years in placebo group was small. The supplement led to a significant reduction in depressive symptoms at month 12, though this effect was not sustained. Aspirin use had a negative interaction effect on cognitive functioning with B supplements. Centre for Clinical Research and Biostatistics (CCRB) Clinical Trials Registry: CUHK_CCT00373.