Dynamics of critical closing pressure explain cerebral autoregulation impairment in acute cerebrovascular disease.

INTRODUCTION: Cerebral autoregulation (CA) is impaired in acute ischemic stroke (AIS) and is associated with worse patient outcomes, but the underlying physiological cause is unclear. This study tests whether depressed CA in AIS can be linked to the dynamic responses of critical closing pressure (CrCP) and resistance area product (RAP). METHODS: Continuous recordings of middle cerebral blood velocity (MCAv, transcranial Doppler), arterial blood pressure (BP), end-tidal CO2 and electrocardiography allowed dynamic analysis of the instantaneous MCAv-BP relationship to obtain estimates of CrCP and RAP. The dynamic response of CrCP and RAP to a sudden change in mean BP was obtained by transfer function analysis. Comparisons were made between younger controls (≤50 years), older controls (>50 years), and AIS patients. RESULTS: Data from 24 younger controls (36.4 ± 10.9 years, 9 male), 38 older controls (64.7 ± 8.2 years, 20 male), and 20 AIS patients (63.4 ± 13.8 years, 9 male) were included. Dynamic CA was impaired in AIS, with lower autoregulation index (affected hemisphere: 4.0 ± 2.3, unaffected: 4.5 ± 1.8) compared to younger (right: 5.8 ± 1.4, left: 5.8 ± 1.4) and older (right: 4.9 ± 1.6, left: 5.1 ± 1.5) controls. AIS patients also demonstrated an early (0-3 second) peak in CrCP dynamic response, that was not influenced by age. CONCLUSION: These early transient differences in the CrCP dynamic response are a novel finding in stroke and occur too early to reflect underlying regulatory mechanisms. Instead, these may be caused by structural changes to cerebral vasculature. .

New Horizons in Peripheral Artery Disease.

Peripheral artery disease (PAD) is the lower limb manifestation of systemic atherosclerotic disease. PAD may initially present with symptoms of intermittent claudication, whilst chronic limb-threatening ischaemia (CLTI), the end stage of PAD, presents with rest pain and/or tissue loss. PAD is an age-related condition present in over 10% of those aged ≥65 in high-income countries. Guidelines regarding definition, diagnosis and staging of PAD and CLTI have been updated to reflect the changing patterns and presentations of disease given the increasing prevalence of diabetes. Recent research has changed guidelines on optimal medical therapy, with low-dose anticoagulant plus aspirin recommended in some patients. Recently published randomised trials highlight where bypass-first or endovascular-first approaches may be optimal in infra-inguinal disease. New techniques in endovascular surgery have increased minimally invasive options for ever more complex disease. Increasing recognition has been given to the complexity of patients with CLTI where a high prevalence of both frailty and cognitive impairment are present and a significant burden of multi-morbidity and polypharmacy. Despite advances in minimally invasive revascularisation techniques and reduction in amputation incidence, survival remains poor for many with CLTI. Shared decision-making is essential, and conservative management is often appropriate for older patients. There is emerging evidence of the benefit of specialist geriatric team input in the perioperative management of older patients undergoing surgery for CLTI. Recent UK guidelines now recommend screening for frailty, cognitive impairment and delirium in older vascular surgery patients as well as recommending all vascular surgery services have support and input from specialist geriatrics teams.

Determinants of the dynamic cerebral critical closing pressure response to changes in mean arterial pressure.

Objective. Cerebral critical closing pressure (CrCP) represents the value of arterial blood pressure (BP) where cerebral blood flow (CBF) becomes zero. Its dynamic response to a step change in mean BP (MAP) has been shown to reflect CBF autoregulation, but robust methods for its estimation are lacking. We aim to improve the quality of estimates of the CrCP dynamic response.Approach. Retrospective analysis of 437 healthy subjects (aged 18-87 years, 218 males) baseline recordings with measurements of cerebral blood velocity in the middle cerebral artery (MCAv, transcranial Doppler), non-invasive arterial BP (Finometer) and end-tidal CO2(EtCO2, capnography). For each cardiac cycle CrCP was estimated from the instantaneous MCAv-BP relationship. Transfer function analysis of the MAP and MCAv (MAP-MCAv) and CrCP (MAP-CrCP) allowed estimation of the corresponding step responses (SR) to changes in MAP, with the output in MCAv (SRVMCAv) representing the autoregulation index (ARI), ranging from 0 to 9. Four main parameters were considered as potential determinants of the SRVCrCPtemporal pattern, including the coherence function, MAP spectral power and the reconstruction error for SRVMAP, from the other three separate SRs.Main results. The reconstruction error for SRVMAPwas the main determinant of SRVCrCPsignal quality, by removing the largest number of outliers (Grubbs test) compared to the other three parameters. SRVCrCPshowed highly significant (p< 0.001) changes with time, but its amplitude or temporal pattern was not influenced by sex or age. The main physiological determinants of SRVCrCPwere the ARI and the mean CrCP for the entire 5 min baseline period. The early phase (2-3 s) of SRVCrCPresponse was influenced by heart rate whereas the late phase (10-14 s) was influenced by diastolic BP.Significance. These results should allow better planning and quality of future research and clinical trials of novel metrics of CBF regulation.

Improving Conversations about Parkinson's Dementia.

BACKGROUND: People with Parkinson's disease (PD) have an increased risk of dementia, yet patients and clinicians frequently avoid talking about it due to associated stigma, and the perception that "nothing can be done about it". However, open conversations about PD dementia may allow people with the condition to access treatment and support, and may increase participation in research aimed at understanding PD dementia. OBJECTIVES: To co-produce information resources for patients and healthcare professionals to improve conversations about PD dementia. METHODS: We worked with people with PD, engagement experts, artists, and a PD charity to open up these conversations. 34 participants (16 PD; 6 PD dementia; 1 Parkinsonism, 11 caregivers) attended creative workshops to examine fears about PD dementia and develop information resources. 25 PD experts contributed to the resources. RESULTS: While most people with PD (70%) and caregivers (81%) shared worries about cognitive changes prior to the workshops, only 38% and 30%, respectively, had raised these concerns with a healthcare professional. 91% of people with PD and 73% of caregivers agreed that PD clinicians should ask about cognitive changes routinely through direct questions and perform cognitive tests at clinic appointments. We used insights from the creative workshops, and input from a network of PD experts to co-develop two open-access resources: one for people with PD and their families, and one for healthcare professionals. CONCLUSION: Using artistic and creative workshops, co-learning and striving for diverse voices, we co-produced relevant resources for a wider audience to improve conversations about PD dementia.

Clinimetrics of performance-based functional outcome measures for vascular amputees: A systematic review.

BACKGROUND: Objective physical performance-based outcome measures (PerBOMs) are essential tools for the holistic management of people who have had an amputation due to vascular disease. These people are often non-ambulatory, however it is currently unclear which PerBOMs are high quality and appropriate for those who are either ambulatory or non-ambulatory. RESEARCH QUESTION: Which PerBOMs have appropriate clinimetric properties to be recommended for those who have had amputations due to vascular disease ('vascular amputee')? DATA SOURCES: MEDLINE, CINAHL, EMBASE, EMCARE, the Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus databases were searched for the terms: "physical performance" or "function", "clinimetric properties", "reliability", "validity", "amputee" and "peripheral vascular disease" or "diabetes". REVIEW METHODS: A systematic review of PerBOMs for vascular amputees was performed following COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology and PRISMA guidelines. The quality of studies and individual PerBOMs was assessed using COSMIN risk of bias and good measurement properties. Overall PerBOM quality was evaluated with a modified GRADE rating. Key clinimetric properties evaluated were reliability, validity, predictive validity and responsiveness. RESULTS: A total of 15,259 records were screened. Forty-eight studies (2650 participants) were included: 7 exclusively included vascular amputees only, 35 investigated validity, 20 studied predictive validity, 23 investigated reliability or internal consistency and 7 assessed responsiveness. Meta-analysis was neither possible nor appropriate for this systematic review in accordance with COSMIN guidelines, due to heterogeneity of the data. Thirty-four different PerBOMs were identified of which only 4 are suitable for non-ambulatory vascular amputees. The Amputee Mobility Predictor no Prosthesis (AMPnoPro) and Transfemoral Fitting Predictor (TFP) predict prosthesis use only. PerBOMs available for assessing physical performance are the One-Leg Balance Test (OLBT) and Basic Amputee Mobility Score (BAMS). CONCLUSION: At present, few PerBOMs can be recommended for vascular amputees. Only 4 are available for non-ambulatory individuals: AMPnoPro, TFP, OLBT and BAMS.

Cognitive testing following transient ischaemic attack: A systematic review of clinical assessment tools.

Cognitive deficits are prevalent after transient ischaemic attack (TIA) and result in loss of function, poorer quality of life and increased risks of dependency and mortality. This systematic review aimed to synthesise the available evidence on cognitive assessment in TIA patients to determine the prevalence of cognitive deficits, and the optimal tests for cognitive assessment. Medline, Embase, PsychINFO and CINAHL databases were searched for relevant articles. Articles were screened by title and abstract. Full-text analysis and quality assessment was performed using the National Institute of Health Tool. Data were extracted on study characteristics, prevalence of TIA deficits, and key study findings. Due to significant heterogeneity, meta-analysis was not possible. Twenty-five full-text articles met the review inclusion criteria. There was significant heterogeneity in terms of cognitive tests used, definitions of cognitive impairment and TIA, time points post-event, and analysis methods. The majority of studies used the Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA) (n = 23). Prevalence of cognitive impairment ranged from 2% to 100%, depending on the time-point and cognitive domain studied. The MoCA was more sensitive than the MMSE for identifying cognitive deficits. Deficits were common in executive function, attention, and language. No studies assessed diagnostic test accuracy against a reference standard diagnosis of cognitive impairment. Recommendations on cognitive testing after TIA are hampered by significant heterogeneity between studies, as well as a lack of diagnostic test accuracy studies. Future research should focus on harmonising tools, definitions, and time-points, and validating tools specifically for the TIA population.

Directional sensitivity of dynamic cerebral autoregulation during spontaneous fluctuations in arterial blood pressure at rest.

Directional sensitivity, the more efficient response of cerebral autoregulation to increases, compared to decreases, in mean arterial pressure (MAP), has been demonstrated with repeated squat-stand maneuvers (SSM). In 43 healthy subjects (26 male, 23.1 ± 4.2 years old), five min. recordings of cerebral blood velocity (bilateral Doppler ultrasound), MAP (Finometer), end-tidal CO2 (capnograph), and heart rate (ECG) were obtained during sitting (SIT), standing (STA) and SSM. A new analytical procedure, based on autoregressive-moving average models, allowed distinct estimates of the autoregulation index (ARI) by separating the MAP signal into its positive (MAP+D) and negative (MAP-D) derivatives. ARI+D was higher than ARI-D (p < 0.0001), SIT: 5.61 ± 1.58 vs 4.31 ± 2.16; STA: 5.70 ± 1.24 vs 4.63 ± 1.92; SSM: 4.70 ± 1.11 vs 3.31 ± 1.53, but the difference ARI+D-ARI-D was not influenced by the condition. A bootstrap procedure determined the critical number of subjects needed to identify a significant difference between ARI+D and ARI-D, corresponding to 24, 37 and 38 subjects, respectively, for SSM, STA and SIT. Further investigations are needed on the influences of sex, aging and other phenotypical characteristics on the phenomenon of directional sensitivity of dynamic autoregulation.

Antihypertensives in dementia: Good or bad for the brain?

Hypertension is associated with both ageing and dementia. Despite this, optimal blood pressure targets in dementia remain unclear. Both high and low blood pressure are associated with poorer cognition. Changes in vascular physiology in dementia may increase the vulnerability of the brain to hypoperfusion associated with antihypertensives. We discuss the potential risks of antihypertensives in the context of altered cerebral haemodynamics, and evidence from antihypertensive trials in dementia. We suggest that individualised blood pressure targets should be the focus for antihypertensive therapy in dementia, rather than strict control to uniform targets extrapolated from trials in cognitively healthy individuals.

Detection of Blood CO2 Influences on Cerebral Hemodynamics Using Transfer Entropy.

Cerebral hemodynamics describes an important physiological system affected by components such as blood pressure, CO2 levels, and endothelial factors. Recently, novel techniques have emerged to analyse cerebral hemodynamics based on the calculation of entropies, which quantifies or describes changes in the complexity of this system when it is affected by a pathological or physiological influence. One recently described measure is transfer entropy, which allows for the determination of causality between the various components of a system in terms of their flow of information, and has shown positive results in the multivariate analysis of physiological signals. This study aims to determine whether conditional transfer entropy reflects the causality in terms of entropy generated by hypocapnia on cerebral hemodynamics. To achieve this, non-invasive signals from 28 healthy individuals who undertook a hyperventilation maneuver were analyzed using conditional transfer entropy to assess the variation in the relevance of CO2 levels on cerebral blood velocity. By employing a specific method to discretize the signals, it was possible to differentiate the influence of CO2 levels during the hyperventilation phase (22.0% and 20.3% increase for the left and right hemispheres, respectively) compared to normal breathing, which remained higher during the recovery phase (15.3% and 15.2% increase, respectively).

Dynamics of the cerebral autoregulatory response to paced hyperventilation assessed using subcomponent and time-varying analyses.

Cerebral blood flow (CBF) can be altered by a change in partial pressure of arterial CO2 (Pco2), being reduced during hyperventilation (HPV). Critical closing pressure (CrCP) and resistance area product (RAP) are parameters that can be studied to understand this change, but their dynamic response has not been investigated during paced HPV (PHPV). Seventy-five participants had recordings at rest and during PHPV. Blood pressure (BP) (Finometer), bilateral CBF velocity (CBFV) (transcranial Doppler), end-tidal CO2 (capnography), and heart rate (HR) were recorded continuously. Subcomponent analysis (SCA) and time-varying CrCP, RAP, and dynamic cerebral autoregulation (autoregulation index, ARI) were estimated by comparing PHPV with poikilocapnia. PHPV caused a change in CBFV (P < 0.01), EtCO2, (P < 0.01), HR (P < 0.001), and RAP (P < 0.01). SCA demonstrated RAP was the main parameter explaining the changes in CBFV due to PHPV. The time-varying step responses for CBFV and RAP during PHPV demonstrated considerable nonstationarity compared with poikilocapnia (P < 0.00001). Although time-varying ARI was temporarily depressed, after 60 s of PHPV it was significantly higher (6.81 ± 1.88) (P < 0.0001) than in poikilocapnia (5.08 ± 1.86). The mean plateau of the RAP step response was -98.3 ± 58.8% 60 s after the onset of PHPV but -71.7 ± 45.0% for poikilocapnia (P = 0.0026), with no corresponding changes in CrCP (P = 0.6). Further work is needed to assess the role of sex and aging in our findings, and the potential for using RAP and CrCP to improve the sensitivity and specificity of CO2 reactivity studies in cerebrovascular conditions.NEW & NOTEWORTHY The dynamic response of critical closing pressure (CrCP) and resistance-area product (RAP) of the cerebral circulation to a step change in mean arterial pressure can shed light on the nonstationary changes induced by paced hyperventilation and the effects of hypocapnia on the autoregulation of cerebral blood flow. Contrary to hypercapnia, where the response is dominated by CrCP, hypocapnia shows an initial depression of cerebral autoregulation, followed by improvements controlled by changes in RAP.

The role of the autonomic nervous system in cerebral blood flow regulation in dementia: A review.

In this review we will examine the role of the autonomic nervous system in the control of cerebral blood flow (CBF) in dementia. Worldwide, 55 million people currently live with dementia, and this figure will increase as the global population ages. Understanding the changes in vascular physiology in dementia could pave the way for novel therapeutic approaches. Reductions in CBF have been demonstrated in multiple dementia sub-types, in addition to increased cerebrovascular resistance and reduced vasoreactivity. Cerebral autoregulation (CA) is a key mechanism for the maintenance of cerebral perfusion, but remains largely intact in cognitive disorders, despite reductions in global and regional CBF. However, the tight coupling between neuronal activity and CBF (neurovascular coupling - NVC) is lost in dementia, which may be a key driver of cognitive dysfunction. Despite numerous studies investigating disturbances in the control of CBF in dementia, less is known about the specific mechanisms responsible for the observed changes. Disturbances could be related to one of a number of pathways and mechanisms including disruption of the autonomic component. In this review we will explore clinical and animal studies, which specifically investigated the autonomic component of CBF control in dementia, drawing on the clinical implications and potential for novel biomarker and therapeutic targets.

The Cognition and Flow Study (CogFlowS): A Mixed Method Evaluation of a Randomized Feasibility Trial of Cognitive Training in Dementia.

BACKGROUND: Cognitive training (CT) may be beneficial in delaying the onset or slowing dementia progression. CT has been evaluated quantitatively and qualitatively, but none have used mixed methods approaches. OBJECTIVE: The aim of this study was to use a mixed methods approach to identify those who may selectively benefit from CT. METHODS: This was an explanatory sequential mixed methods study involving a quantitative randomized trial of 12 weeks multi-domain CT in healthy older adults (HC, n = 20), and people living with mild cognitive impairment (MCI; n = 12) and dementia (n = 24). Quantitative outcomes included: cognition, mood, quality of life, and activities of daily living. 28 (10 HC, 6 MCI, 12 dementia) training participants completed semi-structured interviews with their carer. Quantitative and qualitative data were integrated using joint displays. RESULTS: Three participants dropped out from the training early-on, leaving 25 participants with follow-up data for full integration (10 HC, 6 MCI, 9 dementia). Dropouts and lower adherence to training were more common in dementia participants with greater non-modifiable barriers. High adherers were more resilient to negative emotions, and poorer or fluctuating performance. Integrated analysis found the majority of participants (n = 24) benefited across outcomes, with no clear profile of individuals who benefited more than others. Participants made a number of key recommendations to improve adherence and minimize dropout to CT. CONCLUSION: Reasons for dropout and low adherence were identified, with recommendations provided for the design of CT for dementia. An individual approach to training should be adopted and low adherence should not preclude engagement with CT.

Cerebrovascular responses to somatomotor stimulation in Parkinson's disease: A multivariate analysis.

Parkinson's disease (PD) is a common neurodegenerative disorder, yet little is known about cerebral haemodynamics in this patient population. Previous studies assessing dynamic cerebral autoregulation (dCA), neurovascular coupling (NVC) and vasomotor reactivity (VMR) have yielded conflicting findings. By using multi-variate modelling, we aimed to determine whether cerebral blood flow (CBF) regulation is impaired in PD patients.55 healthy controls (HC) and 49 PD patients were recruited. PD subjects underwent a second recording following a period of abstinence from their anti-Parkinsonian medication. Continuous bilateral transcranial Doppler in the middle cerebral arteries, beat-to-beat mean arterial blood pressure (MAP; Finapres), heart rate (HR; electrocardiogram), and end-tidal CO2 (EtCO2; capnography) were measured. After a 5-min baseline period, a passive motor paradigm comprising 60 s of elbow flexion was performed. Multi-variate modelling quantified the contributions of MAP, ETCO2 and neural stimulation to changes in CBF velocity (CBFV). dCA, VMR and NVC were quantified to assess the integrity of CBF regulation.Neural stimulation was the dominant input. dCA, NVC and VMR were all found to be impaired in the PD population relative to HC (p < 0.01, p = 0.04, p < 0.01, respectively). Our data suggest PD may be associated with depressed CBF regulation. This warrants further assessment using different neural stimuli.

Driving and Parkinson's Disease: A Survey of the Patient's Perspective.

BACKGROUND: Parkinson's disease (PD) is a multi-system disorder that can impact on driving ability. Little is known about how these changes in driving ability affect people with PD, making it difficult for clinicians and carers to offer appropriate support. OBJECTIVE: To assess patient views concerning the effect of PD on their driving ability, the impact of these changes and how they manage them. METHOD: An online survey was created by a team of clinicians, people with PD, their carers, and representatives from Parkinson's UK. People with PD throughout the United Kingdom were invited to participate through Parkinson's UK's website, newsletter and Parkinson's Excellence Network email list. RESULTS: 805 people with PD took part in the survey. We found that the loss of a driving licence had an adverse impact on employment, socialisation, travel costs and spontaneous lifestyle choices. Multiple changes in driving ability related to PD were described, including that impulse control disorders can have an adverse impact on driving. Changes in driving ability caused people to change their driving practices including taking shorter journeys and being less likely to drive at night. Participants advised managing changes in driving ability through planning, vehicle adaptions, maintaining skills and self-assessment. CONCLUSION: This study demonstrates the impact that changes in driving ability can have on the lifestyle of people with PD and reveals the strategies that individuals adopt to manage these changes.

Age-related differences in cerebrovascular responses to cognitive stimulation using a novel method.

Aging is associated with a number of alterations to cerebrovascular function. We aimed to investigate the effect of age on cerebrovascular responses to cognitive stimulation using an objective two-parameter method.Previously derived from a large data-set (135 healthy participants) were applied to a task-activated dataset of 69 healthy participants in five different task conditions. Cumulative response rate (CRR) was calculated as the sum of responses across tasks and hemispheres.There was a significant effect of age (adjusted odds ratio: 1.02 (95% confidence interval: 1.01, 1.04), p = 0.016). There was also a significant effect of task (p = 0.002), but there was no significant interaction between age and task (p = 0.37). Increasing age was associated with increased CRR (adjusted odds ratio: 1.04 (95% confidence interval: 1.01, 1.07), p = 0.009).Using an objective two-parameter method, healthy older adults had increased cerebrovascular responses to cognitive testing.

Investigating the association between depression and cerebral haemodynamics-A systematic review and meta-analysis.

BACKGROUND: Vascular mechanisms may play a role in depression. The aim of this review is to summarise the evidence on alterations in cerebral haemodynamics in depression. METHODS: MEDLINE (1946- present), Embase (1947-present), Web of Science (1970-present), PsycINFO (1984-present), CINAHL (1976-present) and CENTRAL were searched using a predefined search strategy. A meta-analysis was conducted in four groups: 1) global cerebral blood flow (CBF) in ml/min/100 g, 2) CBF velocity (CBFv) in cm/s (maximum flow of left middle cerebral artery, 3) combined CBF and CBFv, 4) Ratio of uptake of Tc 99 m HMPAO (region of interest compared to whole brain). Data are presented as mean difference or standardised mean difference and 95% confidence interval (95% CI). A narrative synthesis of the remaining studies was performed. RESULTS: 87 studies were included. CBF was significantly reduced in depressed patients compared to HC [15 studies, 538 patients, 416 HC, MD: -2.24 (95% CI -4.12, -0.36), p = 0.02, I2 = 64%]. There were no statistically significant differences in other parameters. The narrative synthesis revealed variable changes in CBF in depressed patients, particularly affecting the anterior cingulate and prefrontal cortices. LIMITATIONS: There were various sources of heterogeneity including the severity of depression, use of antidepressant medication, imaging modality used and reporting of outcomes. All of these factors made direct comparisons between studies difficult. CONCLUSIONS: The reduction in CBF in depressed patients compared to HCs may indicate a role for assessment and CBF altering interventions in high-risk groups. However, results were inconsistent across studies, warranting further work to investigate specific subgroups.

Extremes of cerebral blood flow during hypercapnic squat-stand maneuvers.

Squat-stand maneuvers (SSMs) are a popular method of inducing blood pressure (BP) oscillations to reliably assess dynamic cerebral autoregulation (dCA), but their effects on the cerebral circulation remain controversial. We designed a protocol whereby participants would perform SSMs under hypercapnic conditions. Alarmingly high values of cerebral blood flow velocity (CBFV) were recorded, leading to early study termination after the recruitment of a single participant. One healthy subject underwent recordings at rest (5 min sitting, 5 min standing) and during two SSMs (fixed and random frequency). Two sets of recordings were collected; one while breathing room air, one while breathing 5% CO2 . Continuous recordings of bilateral CBFV (transcranial Doppler), heart rate (ECG), BP (Finometer), and end-tidal CO2 (capnography) were collected. Peak values of systolic CBFV were significantly higher during hypercapnia (p < 0.01), and maximal values exceeded 200 cm.s-1 . Estimates of dCA (ARI) during hypercapnia were impaired relative to poikilocapnia (p = 0.03). The phase was significantly reduced under hypercapnic conditions (p = 0.03). Here we report extremely high values of CBFV in response to repeated SSMs during induced hypercapnia, in an otherwise healthy subject. Our findings suggest that protocols performing hypercapnic SSMs are potentially dangerous. We, therefore, urge caution if other research groups plan to undertake similar protocols.

Using complexity-entropy planes to detect Parkinson's disease from short segments of haemodynamic signals.

Objective. There is emerging evidence that analysing the entropy and complexity of biomedical signals can detect underlying changes in physiology which may be reflective of disease pathology. This approach can be used even when only short recordings of biomedical signals are available. This study aimed to determine whether entropy and complexity measures can detect differences between subjects with Parkinsons disease and healthy controls (HCs).Approach. A method based on a diagram of entropy versus complexity, named complexity-entropy plane, was used to re-analyse a dataset of cerebral haemodynamic signals from subjects with Parkinsons disease and HCs obtained under poikilocapnic conditions. A probability distribution for a set of ordinal patterns, designed to capture regularities in a time series, was computed from each signal under analysis. Four types of entropy and ten types of complexity measures were estimated from these distributions. Mean values of entropy and complexity were compared and their classification power was assessed by evaluating the best linear separator on the corresponding complexity-entropy planes.Main results. Few linear separators obtained significantly better classification, evaluated as the area under the receiver operating characteristic curve, than signal mean values. However, significant differences in both entropy and complexity were detected between the groups of participants.Significance. Measures of entropy and complexity were able to detect differences between healthy volunteers and subjects with Parkinson's disease, in poikilocapnic conditions, even though only short recordings were available for analysis. Further work is needed to refine this promising approach, and to help understand the findings in the context of specific pathophysiological changes.

Qualitative Analysis of the Cognition and Flow (CoGFlowS) Study: An Individualized Approach to Cognitive Training for Dementia Is Needed.

BACKGROUND: Cognitive training (CT) may have benefits for both healthy older adults (HC) and those with early cognitive disorders [mild cognitive impairment (MCI) and dementia]. However, few studies have qualitatively evaluated home-based, computerized CT programs. OBJECTIVE: We present the qualitative arm of a feasibility randomized controlled trial evaluating a CT program for HC and people living with MCI or dementia. METHODS: Participants underwent semi-structured interviews after 12 weeks of CT. Where possible, participants were interviewed with their carers. The interview schedule and analysis were underpinned by the health belief model. Interviews were audio-recorded, transcribed, open-coded, and categorized into themes. The analytical framework was developed, and themes were condensed under five major categories: benefits, barriers, threat, self-efficacy, and cues to action. RESULTS: 37 participants underwent interviews. CT was feasible and acceptable to participants. Benefits included: enjoyment, improved awareness, benchmarking cognitive function, reassurance of abilities and giving back control. Barriers were more prevalent among those with dementia: problems with technology, frustration, conflict between patients and carers, apathy and lack of insight, anxiety or low mood, and lack of portability. HC and MCI perceived the severity of dementia risk as high, partially mitigated by CT. Participants living with dementia valued a more individualized approach to training, accounting for baseline characteristics. CONCLUSION: CT was a feasible intervention for HC and people living with dementia and MCI. Benefits were present, but the identified barriers need to be addressed for CT to be implemented successfully.

Cerebral blood flow response rate to task-activation using a novel method can discriminate cognitive impairment from healthy aging.

Objective.A new method to classify individuals as 'responders' to task-activated cerebral blood flow velocity (CBFv) has recently been developed. This study investigated whether CBFv response rate to task-activation is affected by Alzheimer's disease (AD) and mild cognitive impairment (MCI).Approach.The 95th thresholds for cross correlation function peak and variance ratio were derived from 270 unstimulated, healthy hemispheres, and were used to classify the presence of a response to task-activation. Thresholds were applied to five cognitive tasks (attention, verbal fluency, language, visuospatial, memory) in CBFv data from 30 healthy older adults (HC), 35 AD and 22 MCI participants. Cumulative response rate (CRR) was calculated from the sum of responses across five tasks, for both hemispheres. Area under the curve (AUC) was derived from receiver operating characteristic (ROC) curve analysis.Main results. The number of responders differed significantly between tasks (p < 0.005) and diagnostic groups (p = 0.011). On post hoc tests there were more responders in the visuospatial (79%-90%) compared to fluency (45%-80%), language (50%-77%), and memory (44%-70%) tasks bilaterally, and responders were greater in the HC (70%) compared to AD (41%) and MCI (23%) groups to at least eight out of ten tasks. At an optimal threshold of 7.5 out of 10 responses, the AUC-ROC distinguished HC from AD and MCI with a; sensitivity 66% and specificity 70% (AUC = 0.72).Significance. Using a novel method to classify responders to cognitive task-activation, HC demonstrated a higher CRR than those with MCI or AD, and a threshold of <8 responses distinguished healthy ageing from dementia.