Neurovascular coupling in early stage dementia - A case-control study

Abstract

Cerebral amyloid angiopathy (CAA) is frequently found post mortem in Alzheimer's dementia, but often undetected during life especially since in vivo hallmarks of CAA and its vascular damage become overt relatively late in the disease process. Decreased neurovascular coupling to visual stimulation has been put forward as an early MRI marker for CAA disease severity. The current study investigates the role of neurovascular coupling in AD related dementia and its early stages. We included 25 subjective cognitive impairment, 33 mild cognitive impairment and 17 dementia patients and 44 controls. All participants underwent magnetic resonance imaging of the brain and neuropsychological assessment. Univariate general linear modeling analyses were used to assess neurovascular coupling between patient groups and controls. Moreover, linear regression analyses was used to assess the associations between neurovascular coupling and cognition. Our data show that BOLD amplitude is lower in dementia (mean 0.8 ± 0.2, p = 0.001) and MCI patients (mean 0.9 ± 0.3, p = 0.004) compared with controls (mean 1.1 ± 0.2). A low BOLD amplitude was associated with low scores in multiple cognitive domains. We conclude that cerebrovascular dysfunction, most likely due CAA, is an important comorbidity in early stages of dementia and has an independent effect on cognition.

Keywords: Alzheimer’s disease; MRI marker; cerebral amyloid angiopathy; mild cognitive impairment; neurovascular coupling.

Figure 1.

This figure shows an example of the shape of the hemodynamic response curves (blue line) in the occipital lobe after checkerboard stimulation (gray) and subsequent rest (white). The y-axis represents the change in BOLD amplitude in percentage. The x-axis represents time in seconds. The red line represents the individual fitted trapezoid from which the three BOLD parameters were derived. BOLD amplitude was defined as the distance from baseline to the peak response (ceiling). Time to peak was calculated by subtracting A (the beginning of the BOLD signal change) from B (onset of the trapezoid ceiling). Time to baseline was calculated by subtracting C (beginning of the BOLD signal decline) from D (onset of baseline). Additionally, time to signal activation was determined as the time from the beginning of the checkboard stimulation (gray) to A (the beginning of the BOLD signal change). Time to signal deactivation was calculated by subtracting 20 s (duration of the checkerboard stimulation) from C (beginning of the BOLD signal decline).

Figure 2.

This figure shows a typical example of the BOLD activation map superimposed on an anatomical image and the BOLD time course for a random control (75 year old male, BOLD amplitude 1.2), SCI (74 year old male, BOLD amplitude 1.1), MCI (78 year old male, BOLD amplitude 0.8) and dementia patient (74 year old male, BOLD amplitude 0.7).

Figure 3.

This figure shows the distribution of the BOLD amplitude in percentage change (a), time to peak in seconds (b) and time to baseline in seconds (c) for each group separately. Amplitude of the BOLD response show significantly lower values in dementia and MCI in comparison to controls.

Figure 4.

This figure shows the significant associations between BOLD amplitude and global cognitive function (a), memory (b), psychomotor speed (c), executive functioning (d) and language (e). on the x-axis the different cognitive domains in Z-scores and on the y-axis the amplitude of the BOLD response in percentage change.