Study Protocol - Insight 46 Cardiovascular: A Sub-study of the MRC National Survey of Health and Development

Abstract

The commonest causes of dementia are Alzheimer's disease and vascular cognitive impairment. Although these conditions have been viewed as distinct entities, there is increasing evidence that neurodegenerative and vascular pathologies interact or overlap to cause cognitive decline, and that at least in some cases individuals at risk of cognitive decline exhibit abnormal cardiovascular physiology long before emergence of disease. However, the mechanisms linking haemodynamic disturbances with cognitive impairment and the various pathologies that cause dementia are poorly understood. A sub-sample of 502 participants from the Medical Research Council National Survey of Health and Development (NSHD) have participated in the first visit of a neuroscience sub-study referred to as Insight 46, where clinical, cognitive, imaging, and lifestyle data have been collected for the purpose of elucidating the pathological changes preceding dementia. This paper outlines the cardiovascular phenotyping performed in the follow-up visit of Insight 46, with the study participants now aged 74. In addition to standard cardiovascular assessments such as blood pressure measurements, echocardiography, and electrocardiography (ECG), functional Near Infrared Spectroscopy (fNIRS) has been included to provide an assessment of cerebrovascular function. A detailed description of the fNIRS protocol along with preliminary results from pilot data is presented. The combination of lifestyle data, brain structure/function, cognitive performance, and cardiovascular health obtained not only from Insight 46, but also from the whole NSHD provides an exciting opportunity to advance our understanding of the cardiovascular mechanisms underlying dementia and cognitive decline, and identify novel targets for intervention.

Keywords: Dementia; cognitive decline; functional near infrared spectroscopy (fNIRS); vascular cognitive impairment.

Figure 1

Demonstrates the haemodynamic response function (HRF) under different stimulus lengths. Column 1 – boxcar function, indicating onset and duration of stimulus (y = 1). Column 2 – canonical HRF for oxygenated haemoglobin, OHB (red) and deoxygenated haemoglobin, HHB (blue). Column 3 – result of convolving boxcar stimulus function with canonical HRF in a healthy neurovascular unit. Dotted lines correspond to the onset and end of the corresponding stimulus. The * symbol denotes the convolution operator.

Figure 2

Example output from Sphygmocor device showing the blood pressure waveform measured at the right radial artery for participant one of Insight 46. Clinical parameters such as the aortic Systolic Pressure (SP) and aortic Pulse Pressure (PP) are calculated from the average aortic pulse waveform.

Figure 3

(a) Position of sources and detectors with respect to the head obtained using the Polhemus digitization system. The detectors are shown in blue and the sources are shown in yellow (long separation channels) and red (short separation channels). The channels are arranged in quadrants over the left and right prefrontal cortices and the left and right motor cortices. (b) Photograph showing the Brite 24 cap and the Finometer finger cuff in position on a study participant. The channels in the left motor cortex are outlined in magenta in both (a) and (b). RMC, right motor cortex; LMC, left motor cortex; RPFC, right prefrontal cortex; LPFC, left prefrontal cortex.

Figure 4

Change in mean arterial pressure for participant two of Insight 46 during the Colour Trail Test (CTT), Stroop, and finger tapping tasks. The yellow boxes correspond to the time periods where the participant was performing the task.

Figure 5

The change in mean arterial pressure, heart rate, and the concentration of Oxygenated Haemoglobin (OHB) measured during the Stroop task for participant three of Insight 46. Blocks 1–3 of the Stroop task (the cognitive stimuli) are denoted by the yellow rectangles superimposed over each individual graph. Note how all three cardiovascular measures increase in response to the stimuli compared with the baseline readings. Preliminary finger-tapping fNIRS results from an Insight 46 study participant considered to be in good cardiovascular health are shown in Figure 6. The block averaged fNIRS results for each channel are organised in rows according to their location over the brain. Note the strong increase in OHB in Left Motor Cortex (LMC), and the weaker but clear increase in OHB on the Right Motor Cortex (RMC) and Left Prefrontal Cortex (LPFC).

Figure 6

Results from the finger tapping test, participant characteristics, and test performance shown for participant one of Insight 46. The cardiovascular characteristics reported were measured during the standard cardiovascular assessments using echocardiography, ECG, and PWV. The bottom right subplot indicates the axes labels for all other subplots. The red and blue solid lines correspond to the mean Oxygenated Haemoglobin (OHB) and Deoxygenated Haemoglobin (HHB) signals respectively over the five finger-tapping blocks, and the shaded areas represent the standard deviation. Finger tapping occurred over a 10-s period starting at 5 s and ending at 15 s. 0–5 s and 15–20 s are baseline periods. Each of the 16 long-separation channels are displayed for each participant, and are arranged in rows corresponding to position over the brain. Row 1 = Right Motor Cortex (RMC), row 2 = Right Prefrontal Cortex (RPFC), row 3 = Left Prefrontal Cortex (LPFC), row 4 = Left Motor Cortex (LMC).