Baseline Montreal Cognitive Assessment Research Articles

Abstract 68: Impaired Perfusion in Intracranial Atherosclerotic Disease Predicts Cognitive Outcomes

Background: Poor collateral circulation and hypoperfusion may lead to recurrent stroke in intracranial atherosclerotic disease (ICAD). The role of perfusion in silent strokes and potentially insidious cognitive impairment in ICAD is unknown. We used evidence of impaired perfusion at angiography in SAMMPRIS to predict subsequent cognitive changes. Methods: Angiography at enrollment in the SAMMPRIS trial was independently evaluated, blind to clinical data and cognitive testing. Antegrade flow in the symptomatic arterial territory and corresponding collateral flow were scored. Impaired perfusion was defined by poor antegrade and poor collateral flow. Serial testing with the Montreal Cognitive Assessment (MoCA) was done in subjects without aphasia or neglect at baseline, 4 mo, 12 mo and closeout, or until subjects had a clinical stroke endpoint. Results: 207 subjects (median age 61, range 33-81 years; 37% women) had baseline MoCA scores with angiography data on territorial perfusion. Baseline MoCA scores (mean 24.2±4.1) were similar between categories of antegrade flow and collateral circulation. Impaired perfusion was noted in 33/207 (16%). Serial MoCA revealed that changes in cognition over time were different at 4 mo, 12 mo and closeout based on the presence of impaired perfusion at baseline (p<0.001). After more modest (mean MoCA change = 0.5 increase from baseline, p=0.80) early improved cognitive function at 4 mo, those with impaired perfusion had cognitive decline at 12 mo (mean MoCA change, p<0.01) unlike the continued improvement in other subjects. Cognitive changes in those with impaired perfusion were associated with a higher frequency of subsequent stroke in the territory. Conclusions: Impaired perfusion in the symptomatic arterial territory of ICAD predicts cognitive outcomes that may precede recurrent ischemia. Future studies may define the role of noninvasive perfusion imaging in ICAD to predict cognitive trajectories and recurrent stroke.

Global cognition predicts the incidence of poor physical performance among older adults: A cross-national study.

The relationship between physical performance and cognition is well established. However, findings on the relationship between global cognition and the incidence of functional disability has been inconsistent. Using data from the International Mobility in Aging Study, we investigated the relationship between baseline cognitive function and the incidence of poor physical performance 2 years later. A total of 1071 community-dwelling participants (aged 64-75 years) from four sites in Canada and Latin America, with a Short Physical Performance Battery score ≥9 at baseline (good performance) were included. We carried out two sets of analyses, measuring cognition with either the Leganés Cognitive Test or the Montreal Cognitive Assessment. We used three logistic regression models, controlling for either no confounders, sociodemographic confounders or sociodemographic and health confounders. The full model was also stratified by site. A score <9 on the Short Physical Performance Battery indicated poor physical performance. In the fully adjusted model, each 1-point increase in the baseline Leganés Cognitive Test score (range 0-32) was associated with a 10% decrease in the odds of incidence of poor physical performance at the 2-year follow-up (P = 0.019). Likewise, each 1-point increase in the baseline Montreal Cognitive Assessment score (range 0-30) was associated with a 16% decrease in the odds of developing poor physical performance (P = 0.005). When stratified by site, the results were significant at the Latin American sites (P = 0.02), but not at the Canadian sites (P = 0.08). Poor baseline cognition is associated with the incidence of poor physical performance in community-dwelling older adults. To prevent physical disability, interventions addressing both cognitive and physical performance are required. Geriatr Gerontol Int 2020; ••: ••-••.

Carotid Intima-media Thickness, Cognitive Performance and Cognitive Decline in Stroke-free Middle-aged and Older Adults. The Atahualpa Project

Background: Little is known on factors influencing cognitive function in rural communities. Using the Atahualpa Project cohort, we aimed to assess whether the carotid intima-media thickness (cIMT) – used as a surrogate of extracranial carotid atherosclerosis – is associated with cognitive performance and further decline in community-dwelling adults living in a rural setting. Methods: The study included Atahualpa residents aged greater than or equal to 40 years who had ultrasound examination of the extracranial carotid arteries and a baseline Montreal Cognitive Assessment (MoCA), as well as the subset of individuals who also had a follow-up MoCA at least 1 year after baseline. Relationship between cIMT and cognitive function was assessed by means of generalized linear and longitudinal models, adjusted for relevant covariates. Mediation analysis was utilized to establish the proportion of the effect between increased cIMT and cognitive performance, which is mediated by age. Results: A total of 561 individuals were included for the cross-sectional study, and 510 of them were assessed for the prospective cohort. Univariate analysis showed a significant association between increased cIMT and worse cognitive performance (P < .001), which vanishes after considering the effect of age and low scholarity. Causal mediation analysis confirms that age captures 82.6% (95% C.I.: 63.9% to 100%) of the effect of this association. There was no relationship between increased cIMT and cognitive decline in the follow-up. Conclusions: In this rural population, the association between increased cIMT and cognitive dysfunction is mostly mediated by increasing age.

Cognitive changes in women starting anticholinergic medications for overactive bladder: a prospective study.

To assess cognitive changes in women 12months after starting anticholinergic medications for overactive bladder syndrome (OAB). We present a prospective cohort study assessing changes in cognition in women seen in a referral urogynecology practice. We compared women who started anticholinergic OAB medications with women not on anticholinergic OAB medications. The primary outcome was change over time on the Montreal Cognitive Assessment (MOCA) screening score. At enrollment, women completed a baseline MOCA screening, a Geriatric Depression Screen (GDS), and an assessment of medications to create an anticholinergic burden score (ACB). At 3, 6, 9, and 12months after enrollment women were administered the MOCA, GDS, and a review of their medications and medical problems. Statistical analysis was performed using a linear mixed effects model taking into account correlated error terms given multiple MOCA assessments at various time points per patient. A total of 106 women were enrolled, 60 in the OAB medication group and 46 in the control (non-OAB medication) group. The mean age was 77years, 93% of women were Caucasian, and 98% completed high school, with no difference between groups. Over time there was no difference in change of MOCA score between the OAB and control groups when controlling for age, GDS score, and ACB score (p = 0.78). This association did not change when women with a neurological diagnosis were excluded (n = 6). On average MOCA scores for the OAB group increased by 0.76 over 12months and the control group increased 0.39, with no difference between the groups (p = 0.53). We found no changes in MOCA scores between OAB medication and control groups after controlling for age, depression, and polypharmacy after 12months of follow-up.

Cognitive outcomes after unruptured intracranial aneurysm treatment with flow diversion.

Flow diversion is increasingly used to treat a variety of intracranial aneurysms with good safety and efficacy; however, there is some evidence that this treatment is associated with a larger postoperative ischemic burden on imaging than that with other traditional endovascular modalities. These findings typically do not manifest as neurological deficits, but any subtle effects on cognition remain unknown. In this study, the authors describe the neurocognitive performance of a cohort of patients with unruptured intracranial aneurysms (UIAs) before and after treatment with flow diversion. This is the first report of cognitive outcomes following aneurysm treatment with flow diversion. The authors prospectively collected data on cognitive function using the Montreal Cognitive Assessment (MoCA) tool in patients with UIAs who were undergoing endovascular aneurysm treatment with flow diversion between June 2017 and July 2019. Patients completed the MoCA prior to intervention, at the 1-month follow-up after treatment, and again at 6 months after the procedure. All patients with UIAs treated with flow diversion were included regardless of age, aneurysm location, or morphology, unless their functional status precluded completion of the MoCA instrument. A repeated-measures linear mixed-effects model was used to compare preintervention and postintervention cognitive status at the time intervals outlined. Fifty-one patients with 61 aneurysms underwent endovascular aneurysm treatment with flow diversion (mean age 52.5 years, 90.2% females). There was no difference between baseline and postprocedure MoCA scores at any time interval (p > 0.05). The MoCA scores at baseline, 1 month postprocedure, and 6 months postprocedure were 26.1, 26.2, and 26.6, respectively. There was also no difference between pre- and postprocedure scores on any individual domain of the instrument (visuospatial, naming, attention, language, abstraction, delayed recall, and orientation) at any time interval (p > 0.05). Thirty-four patients had follow-up MRI or CT imaging, 5 of whom showed radiographic changes or ischemia. All patients with follow-up clinical evaluation had a 6-month modified Rankin Scale score ≤ 2. Flow diversion is increasingly used in the treatment of intracranial aneurysms. This study suggests that this treatment may not alter neurocognitive function. Larger patient samples and longer follow-ups with other tests of cognitive functions are needed to confirm these findings.

Short-term medical treatment of hypercalcaemia in primary hyperparathyroidism predicts symptomatic response after parathyroidectomy.

Primary hyperparathyroidism is often associated with non-disease-specific symptoms. The aim of this study was to evaluate whether normalization of hypercalcaemia with short-term medical treatment can be used to predict the effects of parathyroidectomy and guide in surgical decision-making. This observational study included patients who received calcimimetic treatment for 4 weeks before parathyroidectomy (30-60 mg daily). A panel of tests was used to assess various aspects of quality of life (European Organisation and Treatment of Cancer QLQ-C30 core questionnaire, Hospital Anxiety and Depression Scale and Positive State of Mind questionnaire), cognitive function (Montreal Cognitive Assessment) and muscle strength (timed-stands test). The tests were carried out at baseline, after 4 weeks of calcimimetic treatment, and at 6 weeks and 6 months after parathyroidectomy. The predictive values of changes during calcimimetic treatment were determined for each test. The study included 110 patients of median age 62 years (91 women). Calcimimetic treatment resulted in normalization of calcium levels and improvements in quality-of-life parameters. The time spent on the timed-stands test was significantly shortened. Eleven of 38 participants with a baseline Montreal Cognitive Assessment score below 26, indicating mild cognitive impairment, reached scores of at least 26 during treatment with calcimimetic. Improvements during treatment with calcimimetic correlated well with postoperative outcomes (positive predictive values 74-96 per cent). The method described in this study may be used to aid surgical decision-making for patients with primary hyperparathyroidism and non-disease-specific symptoms by predicting the effects of normalization of hypercalcaemia.

Cognitive decline is not influenced by the marital status or living arrangements in community-dwelling adults living in a rural setting. A population-based prospective cohort study

Little is known on factors influencing cognitive decline in rural communities. Using the Atahualpa Project cohort, we aimed to assess whether the marital status or living arrangements influenced cognitive decline in community-dwelling adults living in an Ecuadorian rural village. The study included 629 Atahualpa residents aged ≥40 years who had a follow-up Montreal Cognitive Assessment (MoCA) repeated at least one year after baseline. Multivariate longitudinal linear models were fitted to assess differences between the marital status and living arrangements and cognitive decline (as the outcome). A total of 411 participants were married. The remaining 218 were either single, divorced or widowed (191 of them lived with family members and the others lived alone). Enrolled individuals contributed 2088.4 person-years of follow-up (mean: 3.3 ± 1.1 years). The mean baseline MoCA was 22.1 ± 4.5 points and the follow-up MoCA was 20.6 ± 4.8 points (p = 0.001). Overall, 394 (63%) individuals had lower MoCA scores at follow-up. A fully-adjusted longitudinal linear model showed no differences in MoCA decline across married and non-married individuals (β: −0.15; 95% C.I.: −0.55 – 0.26; p = 0.477). When the subset of non-married individuals was taken into account for analyses, multivariate longitudinal linear models showed no differences in the severity of cognitive decline across individuals living alone versus those living with family members (β: 0.28; 95% C.I.: −0.68 – 1.24; p = 0.572). In this study, the marital status or living arrangements had no influence on cognitive decline in the follow-up.

APOE ε4, the door to insulin-resistant dyslipidemia and brain fog? A case study

For decades, scientists have known that carriers of the apolipoprotein E ε4 (APOE ε4) allele (homozygous/heterozygous) are at respectively higher risk for developing Alzheimer's disease (AD). Although previous research reveals that the APOE ε4 variant impacts the clearance capacity and degradation of β-amyloid from the brain, as compared with APOE ε3 (wild type with normal risk) and APOE ε2 (variant with accelerated clearance and reduced risk), little has been documented about APOE ε4's dual role in cholesterol transport, both peripheral and cerebral, and the effects of sluggish APOE ε4 cholesterol transport on cerebral metabolic rate. An understanding of the connection between brain metabolism and brain fat/cholesterol transport may unlock new prevention strategies for treating patients with a comorbidity of metabolic syndrome (MetS) with cognitive impairment. Recent findings suggest that the APOE ε4 carrier impedes the shuttling of lipids from neurons and circumvents the storage of fat within the glia lipid droplets. This sluggish transport of lipids to triglyceride droplets in the glia cells can lead to dangerous reactive oxygen species and hydroxyl-free radicals as lipids are prematurely oxidized.This case study evaluates the effects of a 10-week clinically prescribed ketogenic diet (KD) with a 68-year-old male, heterozygous APOE ε4 carrier, with a dual diagnosis of mild AD and type 2 diabetes (T2DM). The patient was administering both long- and short-acting injectable insulin to mediate his T2DM for 15+ years. Clinical goals of the intervention included increased hypothalamic and peripheral insulin sensitivity as measured via blood ketones with the Abbott Precision Xtra Blood Ketone Meter to confirm metabolic flexibility; controlled plasma glucose as measured via Abbott Precision Xtra Blood Glucose Meter and HgA1c via venous draw; normalization of lipid panel via venous draw and improved memory with restoration of cognitive functionality measured via the Montreal Cognitive Assessment. The Montreal Cognitive Assessment is considered to be a gold standard assessment in the diagnosis of early AD. Physiological biomarkers for T2DM/MetS and cognitive functionality were assessed before/during/after intervention. These measures included HOMA-IR, triglycerides/HDL ratio, HgA1c, fasting glucose, fasting insulin, complete fasting lipid panel and the PEAK mobile application for real-time measurement of cognitive improvement. The results were statistically significant. The patient's baseline Montreal Cognitive Assessment improved from 23/30 (mild AD) to 29/30 (normal ≥ 26). His T2DM was reversed. Pre-intervention HgA1c was 7.8% (T2DM); post intervention HgA1c measured 5.5% (normal). Likewise, the patient achieved statistically significant improvements in the other aforementioned biomarkers of MetS. The results of this case study suggest that a clinically prescribed ketogenic diet has strong potential to restore systemic insulin sensitivity and metabolic flexibility in diabetic, APOE ε4 heterozygous carriers. Mechanisms of action point to normalization of homeostatic negative feedback loops resetting/restoring lipid synthesis/utilization and glucose (insulin)/fatty acid (glucagon) utilization/production in both the body and brain, resulting in increased cerebral metabolism, improved cognition, and reversal of T2DM via renewed cellular insulin sensitivity.

Ketogenic diet rescues cognition in ApoE4+ patient with mild Alzheimer's disease: A case study

It has been established that there is a correlation between Alzheimer's disease and apolipoprotein E, specifically the ApoE4 genetic variant. However, the correlation between Apoe4, insulin resistance and metabolic syndrome (MetS) pathologies still remains elusive. As apolipoprotein E has many important physiological functions, individuals with the ApoE4 allele variant, also known as the Alzheimer's disease gene, are primarily at a greater risk for physiological consequences, specifically cognitive impairment (Chan et al., 2016). In this case study, a 71-year old female, heterozygous for ApoE4 with a family history of Alzheimer's Disease (AD) and the dual diagnosis of mild AD/metabolic syndrome (MetS) was placed on a 10-week nutrition protocol purposed at raising plasma ketones through carbohyrdrate restricted, high fat ketogenic diet (KD), time- restricted eating and physical/cognitive exercise. Primary biomarkers for MetS were measured pre/mid-/post intervention. The MoCA (Montreal Cognitive Assessment) was administered pre/post intervention by a licensed clinical therapist. The results were statistically significant. The HOMA-IR decreased by 75% from 13.9 to 3.48. Triglycerides decreased by 50% from 170mg/dL to 85mg/dL. VLDL dropped by 50% from 34mg/dL to 17mg/dL, and HgA1c decreased from 5.7% to 4.9%. The baseline MoCA score was 21/30; post treatment score was 28/30. The significant results in both MetS biomarkers and the MoCA score suggest that a ketogenic diet may serve to rescue cognition in patients with mild AD. The results of this case study are particularly compelling for ApoE4 positive (ApoE4+) subjects as ketogenic protocols extend hope and promise for AD prevention.

Clinical and neuroimaging risk factors for cognitive decline in community-dwelling older adults living in rural Ecuador. A population-based prospective cohort study.

There is limited information on factors influencing cognitive decline in rural settings from low- and middle-income countries. Using the Atahualpa Project cohort, we aimed to assess the burden of cognitive decline in older adults living in a rural Ecuadorian village. The study included Atahualpa residents aged greater than or equal to 60years who had a follow-up Montreal Cognitive Assessment (MoCA) repeated at least 1year after baseline. MoCA decline was assessed by multivariable longitudinal linear models, adjusted for demographics, days between MoCA tests, cardiovascular risk factors, and neuroimaging signatures of structural brain damage. We included 252 individuals who contributed 923.7 person-years of follow-up (mean: 3.7±0.7years). The mean baseline MoCA was 19.5±4.5 points, and the follow-up MoCA was 18.1±4.9 points (P=0.001). Overall, 154 individuals (61%) had lower MoCA scores at follow-up. The best fitted longitudinal linear model showed a decline of follow-up MoCA from baseline (β: 0.14; 95% CI, 0.0-0.21; P<0.001). High glucose levels, global cortical atrophy, and white matter hyperintensities were independently and significantly associated with greater MoCA decline. This study provides evidence of cognitive decline in older adults living in a rural setting. Main targets for prevention should include glucose control and the control of factors that are deleterious for the development of cortical atrophy and white matter hyperintensities.

Influence of Frailty on Cognitive Decline: A Population-Based Cohort Study in Rural Ecuador

ObjectiveTo assess the influence of frailty on cognitive decline. DesignPopulation-based prospective cohort study. Settings/participantsCommunity-dwelling older adults living in a rural Ecuadorian village, fulfilling the following criteria: age ≥60 years at baseline Montreal Cognitive Assessment (MoCA) and frailty assessment, a baseline brain magnetic resonance imaging, and a follow-up MoCA performed at least 12 months after the baseline. MeasuresFrailty was evaluated by the Edmonton Frailty Scale (EFS) and cognitive performance by MoCA. The relationship between baseline EFS and MoCA decline was assessed by longitudinal linear and fractional polynomial models, adjusted for relevant confounders. The score of the cognitive component of the EFS was subtracted, and an alternative fractional polynomial model was fitted to settle the impact of such cognitive question on the model. ResultsA total of 252 individuals, contributing 923.7 person-years of follow-up (mean: 3.7 ± 0.7 years) were included. The mean EFS score was 4.7 ± 2.5 points. The mean baseline MoCA score was 19.5 ± 4.5 points, and that of the follow-up MoCA was 18.1 ± 4.9 points (P = .001). Overall, 154 (61%) individuals had lower MoCA scores in the follow-up. The best fitted longitudinal linear model showed association between baseline EFS score and MoCA decline (P = .027). There was a continuous increase in MoCA decline in persons with an EFS ≥7 points (nonlinear relationship). Fractional polynomials explained the effect of the EFS on MoCA decline. For the complete EFS score, the β coefficient was 2.43 (95% confidence interval 1.22–3.63). For the effect of the EFS (without its cognitive component) on MoCA decline, the relationship was still significant (β 4.86; 95% confidence interval 2.6–7.13). Conclusions/implicationsOver a 3.7-year period, 61% of older adults living in Atahualpa experienced cognitive decline. Such decline was significantly associated with frailty status at baseline. Region-specific risk factors influencing this relationship should be further studied to reduce its burden in rural settings.

Polysomnography, brain volumetry, and mismatch negativity as early biomarkers of amnestic mild cognitive impairment progression

BackgroundMild cognitive impairment (MCI) is a heterogenous disorder in which a proportion of patients follow stationary or regressive courses while others undergo clinical progression to dementia.MethodsThis study was conducted on 60 amnestic mild cognitive impairment (amMCI) and 20 healthy control subjects submitted to baseline Montreal Cognitive Assessment (MoCA) scale, one-night polysomnography (PSG), hippocampal/entorhinal cortex (HPC/ERC) MRI volumetry, and auditory mismatch negativity (MMN). Fifty-six amMCI subjects continued the study and underwent follow-up MoCA scale 1 year after their baseline evaluation, 17 showed amMCI progression (≥ 3 points decrease in MoCA scale), and 39 had stationary or regressive courses.ResultsProgressive amMCI patients showed reduced sleep efficiency and shortened rapid eye movement (REM) sleep in PSG, decreased HPC/ERC–MRI volumetry and reduced amplitudes with delayed latencies of the MMN evoked potentials.ConclusionsPSG shortened REM sleep, MRI–HPC/ERC volumes reduction, and low amplitude delayed auditory MMN are valuable non-invasive screening predictors of amMCI progression.

Change in Cognition and Other Non-Motor Symptoms With Obstructive Sleep Apnea Treatment in Parkinson Disease.

Parkinson disease (PD) non-motor symptoms are associated with sleep disorders and impair quality of life. Our objective was to assess the effect of obstructive sleep apnea (OSA) treatment using continuous positive airway pressure (CPAP) on PD non-motor symptoms. In this prospective observational study, 67 patients with idiopathic PD underwent polysomnography. Those with moderate-severe OSA were offered CPAP therapy. Subjects were divided into those without OSA (OSA-), and those with OSA (OSA+). Analyses were conducted for 6 and 12 months' follow-up data. At 6 months, those who had used CPAP at home for at least 1 month were considered CPAP users (OSA+CPAP+), whereas those who did not try it, or declined further treatment following a short trial were considered non-users (OSA+CPAP-). For the 12-month analysis, only those still actively using CPAP at 12 months were included in the OSA+CPAP+ group. Non-motor symptom measurements were: Epworth Sleepiness Scale, Montreal Cognitive Assessment (MoCA), Unified Parkinson's Disease Rating Scale part 1 (UPDRS1), Parkinson's Disease Sleep Scale (PDSS), Fatigue Severity Scale, Apathy Scale, Beck Depression Inventory, and Hospital Anxiety and Depression Scale (HADS). Sixty-five participants were re-assessed at least once. At 6 months, 30 participants were categorized as OSA+CPAP+, 11 OSA+CPAP-, and 18 OSA-. At 12 months, 21 were categorized as OSA+CPAP+, 21 OSA+CPAP-, and 17 OSA-. The UPDRS1 and PDSS improved from baseline in OSA+CPAP+ at 6 months (-2.7, standard deviation [SD] 4.0, P = .001, and 7.9, SD 19.0, P = .03, respectively) and 12 months (-4.1, SD 5.4, P = .002, and 11.4, SD 24.4, P = .04, respectively), but not in other groups. The MoCA and HADS-A improved in OSA+CPAP+ at 12 months (1.7, SD 3.5, P = .04, and -2.1, SD 3.8, P = .02, respectively). The MoCA improved in those with low baseline MoCA and those with REM sleep behavior disorder. Mean CPAP use in users at 12 months was 3 hours 36 minutes per night. CPAP treatment of OSA in PD is associated with improved overall non-motor symptoms, sleep quality, anxiety, and global cognitive function over a 12-month period.

Metabolic syndrome marks early risk for cognitive decline with APOE4 gene variation: A case study

A vast amount of research has been done on the APOE4 genetic marker for Alzheimer's disease (AD), but its connection to metabolic processes associated with peripheral insulin resistance and cerebral glucose metabolism is still relatively unknown. The APOE4 allele is the strongest genetic risk factor for developing late-onset Alzheimer’s disease, particularly in individuals who have inherited two copies of the gene (Zhao et al., 2017). In this case study, a 38 year old male with metabolic syndrome (MetS), the APOE4 gene, early stage memory problems and a family history of Alzheimer’s Disease (AD) was placed on a ketogenic diet combined with high intensity interval training (HIIT) for 10 weeks. The primary intervention goal was reduce insulin defect, impaired cerebral and peripheral insulin signaling, associated with metabolic syndrome. Recent research demonstrates that insulin defect competes for space with APOE4 in brain cells, thus exacerbating amyloid pathology (Zhao et al., 2017). Primary biomarkers for metabolic syndrome were measured at baseline and after 10 weeks. The MoCA (Montreal Cognitive Assessment) was administered at baseline and after 10 weeks. The results were statistically significant. The HOMA-IR (homeostatic measure of insulin resistance) decreased by 59% from 4.3 to 1.8. The triglyceride/HDL ratio decreased by 77% from 14.7 to 3.4. Fasting triglycerides were reduced from 573 mg/dL to 167 mg/dL (71% reduction); VLDL decreased from 114.6 mg/dL to 33.4 mg/dL (71% decrease); and fasting insulin was reduced by 55% from 15.6 mU/L to 7.1 mU/L. The baseline MoCA score was 22/30; post treatment score was 30/30. If APOEE4 is the strongest genetic risk factor for developing late-onset Alzheimer's Disease, then implementing a ketogenic diet and high intensity exercise could essentially turn “off” the effects of this APOE4 gene earlier in life for prevention of future neurodegeneration.

Real-world evidence in patient-related outcomes (PROs) of metastatic castrate-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate plus prednisone (AA+P).

196 Background: Oral androgen biosynthesis inhibitor, abiraterone acetate plus prednisone (AA+P), has shown to improve survival and patient-related outcomes (PROs) in clinical trials. The COSMiC study (Canadian Observational Study in Metastatic Cancer of the Prostate; ClinicalTrials.gov: NCT02364531) set out to prospectively amass real-world data on mCRPC patients (pts) managed with AA+P in communities within Canada. Here, we report the interim analysis of their PROs. Methods: At planned data cutoff in Sept 2017 after a median follow-up of 33.8 months, 264 pts were enrolled in 39 sites across Canada. Their FACT-P (Functional Assessment of Cancer Therapy – Prostate) and MoCA (Montreal Cognitive Assessment) were evaluated at baseline as well as at weeks 12, 24, 48 and 72 after AA+P initiation. A 10-point decrease denotes clinically significant degradation in FACT-P and a total MoCA score of &gt; = 26 is considered normal. Descriptive analysis was utilized with continuous variables. Changes from baseline were summarized using mean (SD). Results: At a median age of 77 among 264 pts, 230, 185, 110 and 63 pts were available for analysis at their week 12, 24, 48, and 72 assessments respectively. The mean baseline FACT-P total score was 111.2 (19.44) with a &lt; 3-point absolute change from baseline at subsequent assessments, denoting no clinically significant change in functional status over time. The mean baseline MoCA score was 25.2 (4.50), yet all subsequent assessments scored above 26 and a mean absolute change from baseline of &lt; 1, showing an absence of cognitive decline over time. PSA value was available for 221 pts, 64.3% (142/221) and 34.4% (76/221) achieved a PSA decline of &gt; 50% and 90% respectively. All-grade treatment-related adverse events were reported in 63 pts, with 11% who have had AA+P discontinuation or interruption. Conclusions: COSMiC represents the largest Canadian mCRPC cohort treated with AA+P with real world prospective evaluation of PROs. This data demonstrated the maintenance in quality of life and cognitive status over the course of the study, and underscores the importance of PRO utilization in this complex patient population. Clinical trial information: NCT02364531.

Physical Frailty Is Associated with Longitudinal Decline in Global Cognitive Function in Non-Demented Older Adults: A Prospective Study.

To assess the relationship between physical frailty and subsequent decline in global cognitive function in the non-demented elderly. A prospective population-based study in a west Japanese suburban town, with two-year follow-up. Community-dwellers aged 65 and older without placement in long-term care, and not having a history of dementia, Parkinson's disease and depression at baseline, who participated in the cohort of the Sasaguri Genkimon Study and underwent follow-up assessments two years later (N = 1,045). Global cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Physical frailty was identified according to the following five components: weight loss, low grip strength, exhaustion, slow gait speed and low physical activities. Linear regression models were used to examine associations between baseline frailty status and the MoCA scores at follow-up. Logistic regression models were used to estimate the risk of cognitive decline (defined as at least two points decrease of MoCA score) according to baseline frailty status. Seven hundred and eight non-demented older adults were included in the final analyses (mean age: 72.6 ± 5.5 years, male 40.3%); 5.8% were frail, and 40.8% were prefrail at baseline. One hundred and fifty nine (22.5%) participants experienced cognitive decline over two years. After adjustment for baseline MoCA scores and all confounders, being frail at baseline was significantly associated with a decline of 1.48 points (95% confidence interval [CI], -2.37 to -0.59) in MoCA scores, as compared with non-frailty. Frail persons were over two times more likely to experience cognitive decline (adjusted odds ratio 2.28; 95% CI, 1.02 to 5.08), compared to non-frail persons. Physical frailty is associated with longitudinal decline in global cognitive function in the non-demented older adults over a period of two years. Physically frail older community-dwellers should be closely monitored for cognitive decline that can be sensitively captured by using the MoCA.

Sildenafil Improves Vascular and Metabolic Function in Patients with Alzheimer's Disease.

Alzheimer's disease (AD) is the leading cause of degenerative dementia in the aging population. Patients with AD have alterations in cerebral hemodynamic function including reduced cerebral blood flow (CBF) and cerebral metabolic rate. Therefore, improved cerebrovascular function may be an attractive goal for pharmaceutical intervention in AD. We wished to observe the acute effects of sildenafil on cerebrovascular function and brain metabolism in patients with AD. We used several novel non-invasive MRI techniques to investigate the alterations of CBF, cerebral metabolic rate of oxygen (CMRO2), and cerebrovascular reactivity (CVR) after a single dose of sildenafil administration in order to assess its physiological effects in patients with AD. CBF, CMRO2, and CVR measurements using MRI were performed before and one hour after the oral administration of 50 mg sildenafil. Baseline Montreal Cognitive Assessment score was also obtained. Complete CBF and CMRO2 data were obtained in twelve patients. Complete CVR data were obtained in eight patients. Global CBF and CMRO2 significantly increased (p = 0.03, p = 0.05, respectively) following sildenafil administration. Voxel-wise analyses of CBF maps showed that increased CBF was most pronounced in the bilateral medial temporal lobes. CVR significantly decreased after administration of sildenafil. Our data suggest that a single dose of sildenafil improves cerebral hemodynamic function and increases cerebral oxygen metabolism in patients with AD.

REDUCING COGNITIVE DECLINE WITH PROBUCOL IN ISCHEMIC STROKE PATIENTS WITH HIGH RISK OF CEREBRAL HEMORRHAGE: PICASSO-COG TRIAL

Multiple cerebral microbleeds (CMBs) and prior intracerebral hemorrhage (ICH) are associated with higher risk of cognitive decline after stroke. We aimed to investigate the efficacy of probucol, a lipid-lowering and anti-oxidative agent, to prevent cognitive decline in stroke patients with multiple CMBs or prior ICH. PICASSO-Cog study is a predefined substudy of a randomized controlled clinical trial, PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage (PICASSO). Patients with non-cardioembolic ischemic stroke or transient ischemic attack within 180 days and with previous ICH or multiple CMBs on gradient echo imaging were randomized to probucol versus no probucol groups from 61 institutes of South Korea. Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) was conducted at 4 (baseline), 13, 25, 37, and 49 months after index-stroke. Changes in MMSE and MoCA scores over time from baseline were analyzed using mixed effects model. A total 892 subjects were included in the analysis, with a median follow-up of 20.9 months. Mean age was 64.9 ± 10.8 years, median National Institute of Health Stroke Scale score 1 (IQR 0 - 3), and baseline MMSE score 25.0 ± 4.6. Mean changes of MMSE from baseline to each follow-up was 0.02±2.45 (1st, n=888), -0.15±2.65 (2nd, n=593), -0.24±3.11 (3rd, n=361), and -0.88±3.06 (4th, n=138). The MMSE scores over time showed a favorable trend for probucol treatment, but not significant. Among them, a total of 877 subjects underwent MoCA at least twice after randomization. Baseline MoCA score 19.3 ± 6.2, and mean changes of MoCA from baseline to each follow-up was 0.02 ± 2.83 (1st, n=871), -0.20 ± 3.17 (2nd, n=582), -0.09 ± 3.59 (3rd, n=354), and -0.52 ± 3.49 (4th, n=132). Probucol could significantly prevent cognitive decline in MoCA scores compared to placebo (p=0.01 for treatment effect). These effects were observed in the subgroups without diabetes mellitus, with concomitant lipid-lowering agent, baseline MMSE score > 24, and mild to moderate white matter hyperintensities.

Assessment of quality of life (QOL), cognitive function and depression in a randomized phase II study of abiraterone acetate (ABI) plus prednisone (P) vs enzalutamide (ENZA) for metastatic castrate-resistant prostate cancer (mCRPC).

5036 Background: ABI + P and ENZA treatments are associated with side effects that may impair QOL. ENZA has been associated with cognitive and memory impairment. There has been no direct comparison between these agents and their effect on these domains. Methods: Randomized phase II trial of ABI + P vs ENZA as 1st-line therapy for mCRPC (ClinicalTrials.gov: NCT02125357). FACT-P QOL questionnaire, patient health questionnaire (PHQ-9) and Montreal Cognitive Assessment (MoCA) were completed throughout the study. The proportion of patients with a clinically significant change in FACT-P (10 points total FACT-P score, 3 points FACT-P subscales), worsening of PHQ-9 depression symptom severity (none = 0-4, mild = 5-9, moderate = 10-14, moderate-severe = 15-19, severe ≥20) and decline in MoCA cognitive impairment level (normal = 27-30, mild = 18-26, moderate = 10-17, severe ˂ 10) at week 12 was compared between study arms for this analysis. Results: From 202 patients (pts) accrued, there were 162, 145 and 142 pts with baseline and 12-week FACT-P, PHQ-9 and MoCA assessment. Median baseline FACT-P, PHQ-9 and MoCA scores were similar in both arms. From baseline to 12 weeks, the median total FACT-P score improved in the ABI + P arm (115 to 128, P = 0.02), but there was no change in the ENZA arm (114 to 114, P = 1.00). There was a higher rate of significant worsening for the physical well-being (PWB) subscale for ENZA vs ABI + P (TABLE), but not for the other FACT-P subscales. There was a higher rate of worsening in depression severity in the ENZA arm (TABLE), although worsening to a moderate-severe/severe level occurred in only 2 patients. There was also a trend for worsening in cognitive impairment for the ENZA arm (TABLE). Conclusions: These data suggest there are distinct differences between ABI + P vs ENZA and their effects on QOL, mood symptoms and cognitive function. Clinical trial information: NCT02125357. [Table: see text]

Association Between Neurocognitive Decline and Visual Field Variability in Glaucoma

Visual field variability may impair detection of glaucoma progression over time. Despite the possible overlap between neurocognitive disorders and glaucoma in older individuals, no study has investigated the association between cognitive changes and visual field variability. To evaluate the association between global neurocognitive impairment and visual field variability in patients diagnosed as having glaucoma or glaucoma suspects. This prospective observational cohort study was conducted at the Visual Performance Laboratory, University of California, San Diego. The study involved 211 eyes of 115 patients followed up for a mean (SD) period of 2.5 (0.8) years, ranging from 1.2 to 4.7 years. Data were obtained during the period extending from March 2011 to April 2015, with data analysis conducted from November 2015 to May 2016. Association between cognitive decline and visual field variability. Patients were monitored with standard automated perimetry (SAP) and had longitudinal assessment of cognitive ability using the Montreal Cognitive Assessment (MoCA). Visual field variability was estimated by the SD of the residuals of ordinary least squares linear regressions of SAP mean deviation (MD) values over time. Linear regression models were used to investigate the association between cognitive decline and visual field variability, adjusting for potentially confounding factors. Among the 115 patients, the mean (SD) age at baseline was 67.4 (10.1) years, 63 were men (54.8%), and 86 were white (74.8%). There was a statistically significant association between change in MoCA scores and visual field variability over time. In a univariable model, a 5-point decline in MoCA score was associated with an increase of 0.18 dB in the SD of residuals of SAP MD (R2 = 4.3%; 95% CI, 0.06-0.30; P = .003). In a multivariable model adjusting for baseline MoCA score, mean SAP MD, age, sex, race/ethnicity, educational level, income, and number of SAP tests, each 5-point decline in MoCA score was associated with an increase of 0.23 dB in the SD of residuals of SAP MD (95% CI, 0.11-0.35; P < .001). Cognitive decline was associated with increased visual field variability during follow-up. These findings suggest that screening and monitoring of cognitive dysfunction may be important in the assessment of visual field progression in the context of glaucoma.