Internal consistency and reliability of the lifetime and modified current cognitive activity questionnaires and their association with cognitive performance: a six-year follow up of the Brain in Motion study.

INTRODUCTION: Cognitive activity questionnaires could provide insight into neurocognitive reserve. The Lifetime Cognitive Activities Questionnaire (LCAQ) assesses cognitive activities at four stages of life. The Modified Current Cognitive Activities Questionnaire (CCAQ) assesses current cognitive activities. We examined the construct validity, internal consistency, test-retest reliability, and stability of these questionnaires throughout the Brain in Motion (BIM) study and their relationship with cognitive performance. METHODS: The LCAQ, Montreal Cognitive Assessment (MoCA), and neuropsychological battery were administered at the initial pre-intervention and six-year follow-up. The CCAQ was administered at five timepoints. Construct validity of the CCAQ/LCAQ was assessed using proxies of cognitive engagement (educational attainment and the North American Adult Reading Test [NAART]). Cronbach alpha analysis determined internal consistency. LCAQ reliability was established by comparing the pre-intervention and six-year follow-up. CCAQ reliability was determined by comparing both pre-intervention assessments, correlations throughout BIM determined stability. A multiple linear regression investigated the associations between cognitive engagement and cognitive domains derived from a principal component analysis. RESULTS: MoCA scores at the initial pre-intervention (27.49 ± 1.46) and six-year follow up (26.53 ± 2.08). The LCAQ and CCAQ correlated with educational attainment and the NAART. The LCAQ (n = 266) produced an alpha of 0.90 (20 items). The CCAQ (n = 261) resulted in an alpha of 0.71 (25 items). LCAQ scores (n = 94) at the initial pre-intervention and six-year follow-up were correlated. CCAQ (n = 94) scores at the initial pre-intervention correlated with scores at all five other timepoints. The multiple linear regression revealed associations between the CCAQ and verbal memory/attention. The NAART was associated with processing speed, concept formation, and verbal memory/attention. CONCLUSIONS: In the absence of cognitive decline, these questionnaires exhibit significant construct validity, internal consistency, test-retest reliability, and the CCAQ displayed stability. The NAART and CCAQ were associated with neuropsychological performance. Our findings support future use of these questionnaires and exemplify the neuroprotective role of cognitive engagement.

Arterial spin labelling reveals multi-regional cerebral hypoperfusion in patients with transient ischemic attack that are unrelated to ischemia location: A proof-of-concept study.

Background and Aims: Patients with transient ischemic attack (TIA) have a substantially increased risk of early dementia. In this exploratory study, we aim to determine whether patients with TIA have 1) measurable regional cerebral hypoperfusion unrelated to the location of ischemia, and 2) determine the relationship of regional cerebral blood flow (rCBF) with their cognitive profiles. Methods: Patients with TIA (N = 49) and seventy-nine (N = 79) age and sex matched controls underwent formal neuropsychological testing and MRI. Quantitative arterial spin labelling rCBF maps (mL/min/100 g) were registered to the corresponding high resolution T1-weighted image. Linear regression was used to determine the association between demographic, clinical and cognitive variables and rCBF. Results: Patients with TIA had significantly (p < 0.05) lower cognitive scores in the MMSE, MOCA, ACE-R, WAIS-IV DS Coding and Trail Making Tests A and B compared to controls. TIA patients had significantly lower rCBF in the left entorhinal cortex (p = 0.03), right posterior cingulate (p = 0.04), and right precuneus (p = 0.05), after adjusting for age and sex, that were unrelated to the regional anatomical volume and DWI positivity. Regional hypoperfusion in the right posterior cingulate and right precuneus was associated with impaired visual memory (BVMT total, p = 0.05 for both regions) and slower processing speed (TMT A, p = 0.04 and p = 0.01), respectively after adjusting for age and sex. Conclusions: TIA patients have patterns of regional hypoperfusion in multiple cortical regions unrelated to the parcellated regional anatomical volume or the presence of a DWI lesion. Regional hypoperfusion in patients with TIA may be an early marker conferring risk of future cognitive decline that needs to be confirmed by future studies.

The Brain in Motion II Study: study protocol for a randomized controlled trial of an aerobic exercise intervention for older adults at increased risk of dementia.

BACKGROUND: There remains no effective intervention capable of reversing most cases of dementia. Current research is focused on prevention by addressing risk factors that are shared between cardiovascular disease and dementia (e.g., hypertension) before the cognitive, functional, and behavioural symptoms of dementia manifest. A promising preventive treatment is exercise. This study describes the methods of a randomized controlled trial (RCT) that assesses the effects of aerobic exercise and behavioural support interventions in older adults at increased risk of dementia due to genetic and/or cardiovascular risk factors. The specific aims are to determine the effect of aerobic exercise on cognitive performance, explore the biological mechanisms that influence cognitive performance after exercise training, and determine if changes in cerebrovascular physiology and function persist 1 year after a 6-month aerobic exercise intervention followed by a 1-year behavioural support programme (at 18 months). METHODS: We will recruit 264 participants (aged 50-80 years) at elevated risk of dementia. Participants will be randomly allocated into one of four treatment arms: (1) aerobic exercise and health behaviour support, (2) aerobic exercise and no health behaviour support, (3) stretching-toning and health behaviour support, and (4) stretching-toning and no health behaviour support. The aerobic exercise intervention will consist of three supervised walking/jogging sessions per week for 6 months, whereas the stretching-toning control intervention will consist of three supervised stretching-toning sessions per week also for 6 months. Following the exercise interventions, participants will receive either 1 year of ongoing telephone behavioural support or no telephone support. The primary aim is to determine the independent effect of aerobic exercise on a cognitive composite score in participants allocated to this intervention compared to participants allocated to the stretching-toning group. The secondary aims are to examine the effects of aerobic exercise on a number of secondary outcomes and determine whether aerobic exercise-related changes persist after a 1-year behavioural support programme (at 18 months). DISCUSSION: This study will address knowledge gaps regarding the underlying mechanisms of the pro-cognitive effects of exercise by examining the potential mediating factors, including cerebrovascular/physiological, neuroimaging, sleep, and genetic factors that will provide novel biologic evidence on how aerobic exercise can prevent declines in cognition with ageing. TRIAL REGISTRATION: ClinicalTrials.gov NCT03035851 . Registered on 30 January 2017.

Genetic Risk, Vascular Function, and Subjective Cognitive Complaints Predict Objective Cognitive Function in Healthy Older Adults: Results From the Brain in Motion Study.

Aging is associated with subjective memory complaints. Approximately half of those with subjective memory complaints have objective cognitive impairment. Previous studies have provided evidence of an association between genetic risk for Alzheimer's disease (AD) and dementia progression. Also, aging is a significant risk factor for vascular pathology that may underlie at least some of the cognitive changes. This study investigates the relative contribution of subjective cognitive complaints (SCC), vascular function, and genetic risk for dementia in predicting objective cognitive performance. Multiple regression and relative importance analysis were used to investigate the relative contribution of vascular function, self-reported SCC, and dementia genetic risk, in predicting objective cognition in a sample of 238 healthy community-dwelling older adults. Age, sex, premorbid cognitive abilities, subjective verbal memory complaints, higher cerebrovascular blood flow during submaximal exercise, and certain dementia risk alleles were significant predictors of worse objective verbal memory performance (p < 0.001, R 2 = 35.2-36.4%). Using relative importance analysis, subjective verbal memory complaints, and certain dementia risk alleles contributed more variance than cerebrovascular measures. These results suggest that age-related changes in memory in healthy older adults can be predicted by subjective memory complaints, genetic risk, and to a lesser extent, cerebrovascular function.

Aerobic exercise improves cognition and cerebrovascular regulation in older adults.

OBJECTIVE: To test the hypothesis that aerobic exercise is associated with improvements in cognition and cerebrovascular regulation, we enrolled 206 healthy low-active middle-aged and older adults (mean ± SD age 65.9 ± 6.4 years) in a supervised 6-month aerobic exercise intervention and assessed them before and after the intervention. METHODS: The study is a quasi-experimental single group pre/postintervention study. Neuropsychological tests were used to assess cognition before and after the intervention. Transcranial Doppler ultrasound was used to measure cerebral blood flow velocity. Cerebrovascular regulation was assessed at rest, during euoxic hypercapnia, and in response to submaximal exercise. Multiple linear regression was used to examine the association between changes in cognition and changes in cerebrovascular function. RESULTS: The intervention was associated with improvements in some cognitive domains, cardiorespiratory fitness, and cerebrovascular regulation. Changes in executive functions were negatively associated with changes in cerebrovascular resistance index (CVRi) during submaximal exercise (ß = -0.205, p = 0.013), while fluency improvements were positively associated with changes in CVRi during hypercapnia (ß = 0.106, p = 0.03). CONCLUSION: The 6-month aerobic exercise intervention was associated with improvements in some cognitive domains and cerebrovascular regulation. Secondary analyses showed a novel association between changes in cognition and changes in cerebrovascular regulation during euoxic hypercapnia and in response to submaximal exercise.

Aerobic exercise increases cortisol awakening response in older adults.

Evidence from both preclinical and clinical studies suggests aerobic exercise may dampen age-related decline in cognitive performance. Alterations in hypothalamic-pituitary-adrenal (HPA) axis function and reactivity may be a mechanism by which aerobic exercise benefits cognitive performance, and reduces perceived stress. This investigation was completed as an ancillary investigation of the Brain in Motion (BIM) study, a 6-month supervised aerobic exercise intervention. Participants were generally healthy and screened for inclusion/exclusion criteria for the parent study. Thirty-eight participants were recruited (Mean age = 65.0 [SD = 5.1]; 60% female) and the final longitudinal sample was 32 participants. Participants provided a passive drool sample at: waking, 15, 30, and 45 min post-waking to assess the cortisol awakening response (CAR) and 3, 6, 9, and 12 h post-waking to assess daily area under the curve for cortisol. Salivary cortisol was quantified by liquid chromatography coupled to tandem mass spectrometry. The exercise intervention increased CAR but no differences were observed in daily AUC. In addition, larger increases in CAR were positively associated with greater decreases in subjective stress. Thus, aerobic exercise improved the CAR in otherwise healthy, but sedentary older adults and greater improvements in CAR were associated with greater reductions in perceived stress.

The Attention Network Test-Interaction (ANT-I): reliability and validity in healthy older adults.

The Attention Network Test (ANT) is a frequently used computer-based tool for measuring the three attention networks (alerting, orienting, and executive control). We examined the psychometric properties of performance on a variant of the ANT, the Attention Network Test-Interaction (ANT-I) in healthy older adults (N = 173; mean age = 65.4, SD = 6.5; obtained from the Brain in Motion Study, Tyndall et al. BMC Geriatr 13:21, 2013. doi: 10.1186/1471-2318-13-21) to evaluate its usefulness as a measurement tool in both aging and clinical research. In terms of test reliability, split-half correlation analyses showed that all network scores were significantly reliable, although the strength of the correlations varied across networks as seen before (r = 0.29, 0.70, and 0.68, for alerting, orienting, and executive networks, respectively, p's < 0.05). In terms of construct validity, ANOVAs confirmed that each network score was significant (18.3, 59.4, and 109.2 ms for the alerting, orienting, and executive networks, respectively, p's < 0.01) and that these scores were generally independent from each other. Importantly, for criterion validity, a series of hierarchical linear regressions showed that the executive network score, in addition to demographic information, was a significant predictor of performance on tests of conflict resolution as well as verbal memory and retrieval (ß = -0.165 and -0.184, p's < 0.05, respectively). These results provide new information regarding the reliability and validity of ANT-I test performance in a healthy older adult population. The results provide insights into the psychometrics of the ANT-I and its potential utility in clinical research settings.

Association between Lifetime Physical Activity and Cognitive Functioning in Middle-Aged and Older Community Dwelling Adults: Results from the Brain in Motion Study.

To determine if total lifetime physical activity (PA) is associated with better cognitive functioning with aging and if cerebrovascular function mediates this association. A sample of 226 (52.2% female) community dwelling middle-aged and older adults (66.5 ± 6.4 years) in the Brain in Motion Study, completed the Lifetime Total Physical Activity Questionnaire and underwent neuropsychological and cerebrovascular blood flow testing. Multiple robust linear regressions were used to model the associations between lifetime PA and global cognition after adjusting for age, sex, North American Adult Reading Test results (i.e., an estimate of premorbid intellectual ability), maximal aerobic capacity, body mass index and interactions between age, sex, and lifetime PA. Mediation analysis assessed the effect of cerebrovascular measures on the association between lifetime PA and global cognition. Post hoc analyses assessed past year PA and current fitness levels relation to global cognition and cerebrovascular measures. Better global cognitive performance was associated with higher lifetime PA (p=.045), recreational PA (p=.021), and vigorous intensity PA (p=.004), PA between the ages of 0 and 20 years (p=.036), and between the ages of 21 and 35 years (p.5), but partially mediated the relation between current fitness and global cognition. This study revealed significant associations between higher levels of PA (i.e., total lifetime, recreational, vigorous PA, and past year) and better cognitive function in later life. Current fitness levels relation to cognitive function may be partially mediated through current cerebrovascular function.

Cognitive impairment associated with carcinoid syndrome.

OBJECTIVES: To evaluate the cognitive performance of patients with carcinoid syndrome (CS) compared with population norms and cancer patients with non-neuroendocrine (non-NET) liver metastases. BACKGROUND: The release of serotonin into the systemic circulation from metastatic small bowel neuroendocrine tumors (SB NET) causes CS. Many patients with CS followed in a multidisciplinary NET clinic seemed to exhibit a unique cognitive impairment. Because serotonin is known to influence a range of cognitive function, the question arouse as to whether cognitive impairment is another manifestation of CS. METHODS: Patients were recruited from the multidisciplinary NET and the hepatobilary cancer clinics at the cancer center. The CS group consisted of patients with proven SB NETs metastatic to liver; the cancer comparison group consisted of patients with liver metastases from non-NET cancer. All completed a self-reported cognitive questionnaire and a battery of 6 standardized neurocognitive tests. Both groups were compared to age/sex/educational-matched norms. RESULTS: Thirty-six patients with CS and 20 with non-NET metastases were enrolled. Patients with CS reported greater cognitive dysfunction in all cognitive domains than both norms and the comparison cancer group. On cognitive testing, patients with CS demonstrated weakness in initiation, processing speed, visual memory, cognitive efficiency, and delayed verbal recall compared with norms. Although the patients with non-NET cancer also demonstrated some cognitive dysfunction compared with norms, the patients with CS did significantly worse on delayed recall (P = 0.03) and marginally slower on speeded mental flexibility (P = 0.097) compared with patients with non-NET cancer. CONCLUSION: This study confirmed our clinical observation that patients with CS suffer from cognitive impairment that is different from the non-NET cancer group and population norms.

The brain-in-motion study: effect of a 6-month aerobic exercise intervention on cerebrovascular regulation and cognitive function in older adults.

BACKGROUND: Aging and physical inactivity are associated with declines in some cognitive domains and cerebrovascular function, as well as an elevated risk of cerebrovascular disease and other morbidities. With the increase in the number of sedentary older Canadians, promoting healthy brain aging is becoming an increasingly important population health issue. Emerging research suggests that higher levels of physical fitness at any age are associated with better cognitive functioning and this may be mediated, at least in part, by improvements in cerebrovascular reserve. We are currently conducting a study to determine: if a structured 6-month aerobic exercise program is associated with improvements or maintenance of both cerebrovascular function and cognitive abilities in older individuals; and, the extent to which any changes seen persist 6 months after the completion of the structured exercise program. METHODS/DESIGN: Two hundred and fifty men and women aged 55-80 years are being enrolled into an 18-month combined quasi-experimental and prospective cohort study. Participants are eligible for enrollment into the study if they are inactive (i.e., not participating in regular physical activity), non-smokers, have a body mass index <35.0 kg/m(2), are free of significant cognitive impairment (defined as a Montreal Cognitive Assessment score of 24 or more), and do not have clinically significant cardiovascular, cerebrovascular disease, or chronic obstructive pulmonary airway disease. Repeated measurements are done during three sequential six-month phases: 1) pre-intervention; 2) aerobic exercise intervention; and 3) post-intervention. These outcomes include: cardiorespiratory fitness, resting cerebral blood flow, cerebrovascular reserve, and cognitive function. DISCUSSION: This is the first study to our knowledge that will examine contemporaneously the effect of an exercise intervention on both cerebrovascular reserve and cognition in an older population. This study will further our understanding of whether cerebrovascular mechanisms might explain how exercise promotes healthy brain aging. In addition our study will address the potential of increasing physical activity to prevent age-associated cognitive decline.

Cerebrovascular reserve: the link between fitness and cognitive function?

Better physical fitness in later life is associated positively with cognitive functioning. Novel data suggest that this association is mediated, in part, by increases in brain perfusion and the ability of cerebral blood vessels to respond to demand. This review presents evidence on the beneficial effects of exercise on cerebrovascular and cognitive health with aging and explores potential underlying vascular-related mechanisms.

Some supplementary methods for the analysis of WAIS-IV index scores in neuropsychological assessment.

OBJECTIVES: To develop supplementary methods for the analysis of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) in neuropsychological assessment. DESIGN AND METHODS: Psychometric. RESULTS: The following methods are made available: (a) provision of traditional confidence intervals (CIs) on index scores, (b) expression of the endpoints of CIs as percentile ranks; (c) quantification of the number of abnormally low index scores exhibited by a case and accompanying estimate of the percentage of the normative population expected to exhibit at least this number of low scores; (d) quantification of the reliability and abnormality of index score deviations from an individual's index score mean (thereby offering an alternative to the pairwise approach to index score comparisons available in the WAIS-IV manual); (e) provision of CIs on an individual's deviation scores or pairwise difference scores, (f) estimation of the percentage of the normative population expected to exhibit at least as many abnormal deviations or abnormal pairwise differences as a case; and (g) calculation of a case's Mahalanobis distance index (MDI), thereby providing a multivariate estimate of the overall abnormality of an index score profile. With the exception of the MDI, all the methods can be applied using tables provided in this paper. However, for ease and speed of application, and to reduce the possibility of clerical error, all the methods have also been implemented in a computer program. CONCLUSIONS: The methods are useful for neuropsychological interpretation of the WAIS-IV.

Impairment of cognitive function reported by patients suffering from carcinoid syndrome.

BACKGROUND: Carcinoid syndrome (CS) is characterized by symptoms of diarrhea, flushing, bronchospasm, and valvular heart disease. It has been our impression that patients with CS also exhibit features of cognitive impairment. The purpose of this pilot study was to evaluate if symptoms of cognitive impairment were reported by patients with CS. METHODS: Patients with proven CS completed a 38-question multiple-ability self-report questionnaire (MASQ) to assess symptoms in five cognitive domains: language skills, attention/concentration (A/C), visual-perceptual function, visual memory, and verbal memory. Patients subsequently underwent neurocognitive assessment using a battery of six standardized tests. Results of the MASQ and the cognitive test were compared to published results for healthy individuals. RESULTS: Twenty-one patients with CS were studied. MASQ symptom scores were higher than published norms in all five cognitive domains. Patients reported greatest difficulty with verbal memory (mean +/- SD = 2.74 +/- 0.5), followed by A/C (2.41 +/- 0.65), language (2.31 +/- 0.55), visual memory (2.30 +/- 0.65), and visual-perceptual function (2.17 +/- 0.59). In contrast, neurocognitive tests for verbal memory immediate recall, visual memory, language, and executive function were within the normal range. CS patients, however, scored lower than expected in tests of verbal memory delayed recall and visual-perceptual function. CONCLUSIONS: Patients with CS report high levels of symptoms of impairment in all cognitive domains; however, on formal neurocognitive testing, patients scored lower than expected only in tests of verbal memory delayed recall and visual-perceptual function. These findings appear to confirm our clinical impression that cognitive impairment may be an additional feature of CS. Further studies are needed to confirm and elucidate the cause of this cognitive impairment.

Effects of cardiorespiratory fitness and cerebral blood flow on cognitive outcomes in older women.

The mechanisms by which aerobic fitness confers beneficial effects on cognition with aging are unclear but may involve cerebrovascular adaptations. In a cross-sectional study of women from the community (n=42; age range=50-90 years), we sought to determine whether physical fitness is associated with higher cerebrovascular function, and its relationship to cognition. Main outcome measures included resting cerebral blood flow, cerebrovascular reserve, physical fitness (i.e., VO2max) and cognition. Physically fit women had lower resting mean arterial pressure (MAP) and higher cerebrovascular conductance (CVC) than sedentary women. Overall cognition was negatively correlated with age and positively correlated with VO2max. VO2max was a predictor of resting CVC and MAP, and CVC and MAP when end-tidal gases were held constant at near-resting values. MAP and CVC were predictors of cognition. This study identified strong associations between physical fitness, vascular function and cognition, and provides new understanding regarding the mechanisms by which fitness positively impacts cognition with aging. The implications of this research are considerable and warrant future investigation.

WAIS-III percentile scores by education and sex for U.S. and Canadian populations.

Tables are presented for the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) IQ and index scores by education level for both the U.S. and Canadian normative samples. This allows clinicians to provide more accurate identification of relative strengths or weaknesses, compared to expectations from an individual's background, rather than the general population. Because sex differences are notable on the Processing Speed Index, data for this measure are presented separately. The similarities and differences between the two national samples are noted, with particular reference to the relatively weaker demographic effects found in the Canadian sample.

Values for comparison of WAIS-III index scores with overall means.

The Wechsler Adult Intelligence Scale--Third Edition (WAIS-III; Wechsler, 1997b) provides factor-based index scores but allows only for pairwise comparison of these scores, producing inflated Type I error rates and reducing profile interpretability. This article provides tables for simultaneous comparison to the overall mean index score, thus reducing error rates and aiding interpretation. The Working Memory Index or Processing Speed Index can also be specifically compared when an individual is believed to have a condition, such as a learning disability or traumatic brain injury, associated with the selective depression of these indexes. Tables for the infrequency of specific differences are also provided, allowing the practitioner to note how unusual an obtained difference is in the general population.