Diastolic Blood Pressure and Cognitive Function in Adults With Achieved Systolic Blood Pressure Below 130 mm Hg: Insights From the SPRINT-MIND Trial.

The potential benefits or harms of intensive systolic blood pressure (BP) control on cognitive function and cerebral blood flow in individuals with low diastolic blood pressure (DBP) remain unclear. We conducted a post hoc analysis of the SPRINT MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension) that randomly assigned hypertensive participants to an intensive (<120 mm Hg; n=4278) or standard (<140 mm Hg; n=4385) systolic blood pressure target. We evaluated the effects of BP intervention on cognitive outcomes and cerebral blood flow across baseline DBP quartiles. Participants in the intensive group had a lower incidence rate of probable dementia or mild cognitive impairment than those in the standard group, regardless of DBP quartiles. The hazard ratio of intensive versus standard target for probable dementia or mild cognitive impairment was 0.91 (95% CI, 0.73-1.12) in the lowest DBP quartile and 0.70 (95% CI, 0.48-1.02) in the highest DBP quartile, respectively, with an interaction P value of 0.24. Similar results were found for probable dementia (interaction P=0.06) and mild cognitive impairment (interaction P=0.80). The effect of intensive treatment on cerebral blood flow was not modified by baseline DBP either (interaction P=0.25). Even among participants within the lowest DBP quartile, intensive versus standard BP treatment resulted in an increasing trend of annualized change in cerebral blood flow (+0.26 [95% CI, -0.72 to 1.24] mL/[100 g·min]). Intensive BP control did not appear to have a detrimental effect on cognitive outcomes and cerebral perfusion in patients with low baseline DBP. URL: https://www. gov; Unique identifier: NCT01206062.

Low soluble amyloid-β 42 is associated with smaller brain volume in Parkinson's disease

Increase in Cerebral Blood Flow After Catheter Ablation of Atrial Fibrillation.

Little is known about the associations of strict blood pressure (BP) control with microstructural changes in small vessel disease markers. To investigate the regional associations of intensive vs standard BP control with small vessel disease biomarkers, such as white matter lesions (WMLs), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF). The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter randomized clinical trial that compared intensive systolic BP (SBP) control (SBP target <120 mm Hg) vs standard control (SBP target <140 mm Hg) among participants aged 50 years or older with hypertension and without diabetes or a history of stroke. The study began randomization on November 8, 2010, and stopped July 1, 2016, with a follow-up duration of approximately 4 years. A total of 670 and 458 participants completed brain magnetic resonance imaging at baseline and follow-up, respectively, and comprise the cohort for this post hoc analysis. Statistical analyses for this post hoc analysis were performed between August 2020 and October 2022. At baseline, 355 participants received intensive SBP treatment and 315 participants received standard SBP treatment. The main outcomes were regional changes in WMLs, FA, MD (in white matter regions of interest), and CBF (in gray matter regions of interest). At baseline, 355 participants (mean [SD] age, 67.7 [8.0] years; 200 men [56.3%]) received intensive BP treatment and 315 participants (mean [SD] age, 67.0 [8.4] years; 199 men [63.2%]) received standard BP treatment. Intensive treatment was associated with smaller mean increases in WML volume compared with standard treatment (644.5 mm3 vs 1258.1 mm3). The smaller mean increases were observed specifically in the deep white matter regions of the left anterior corona radiata (intensive treatment, 30.3 mm3 [95% CI, 16.0-44.5 mm3]; standard treatment, 80.5 mm3 [95% CI, 53.8-107.2 mm3]), left tapetum (intensive treatment, 11.8 mm3 [95% CI, 4.4-19.2 mm3]; standard treatment, 27.2 mm3 [95% CI, 19.4-35.0 mm3]), left superior fronto-occipital fasciculus (intensive treatment, 3.2 mm3 [95% CI, 0.7-5.8 mm3]; standard treatment, 9.4 mm3 [95% CI, 5.5-13.4 mm3]), left posterior corona radiata (intensive treatment, 26.0 mm3 [95% CI, 12.9-39.1 mm3]; standard treatment, 52.3 mm3 [95% CI, 34.8-69.8 mm3]), left splenium of the corpus callosum (intensive treatment, 45.4 mm3 [95% CI, 25.1-65.7 mm3]; standard treatment, 83.0 mm3 [95% CI, 58.7-107.2 mm3]), left posterior thalamic radiation (intensive treatment, 53.0 mm3 [95% CI, 29.8-76.2 mm3]; standard treatment, 106.9 mm3 [95% CI, 73.4-140.3 mm3]), and right posterior thalamic radiation (intensive treatment, 49.5 mm3 [95% CI, 24.3-74.7 mm3]; standard treatment, 102.6 mm3 [95% CI, 71.0-134.2 mm3]). This study suggests that intensive BP treatment, compared with standard treatment, was associated with a slower increase of WMLs, improved diffusion tensor imaging, and FA and CBF changes in several brain regions that represent vulnerable areas that may benefit from more strict BP control. ClinicalTrials.gov Identifier: NCT01206062.

Kidney Disease, Hypertension Treatment, and Cerebral Perfusion and Structure

Upon ascent to high altitude, cerebral blood flow (CBF) rises substantially before returning to sea-level values. The underlying mechanisms for these changes are unclear. We examined three hypotheses: (1) the balance of arterial blood gases upon arrival at and across 2 weeks of living at 5050 m will closely relate to changes in CBF; (2) CBF reactivity to steady-state changes in CO2 will be reduced following this 2 week acclimatisation period, and (3) reductions in CBF reactivity to CO2 will be reflected in an augmented ventilatory sensitivity to CO2. We measured arterial blood gases, middle cerebral artery blood flow velocity (MCAv, index of CBF) and ventilation () at rest and during steady-state hyperoxic hypercapnia (7% CO2) and voluntary hyperventilation (hypocapnia) at sea level and then again following 2–4, 7–9 and 12–15 days of living at 5050 m. Upon arrival at high altitude, resting MCAv was elevated (up 31 ± 31%; P < 0.01; vs. sea level), but returned to sea-level values within 7–9 days. Elevations in MCAv were strongly correlated (R2= 0.40) with the change in ratio (i.e. the collective tendency of arterial blood gases to cause CBF vasodilatation or constriction). Upon initial arrival and after 2 weeks at high altitude, cerebrovascular reactivity to hypercapnia was reduced (P < 0.05), whereas hypocapnic reactivity was enhanced (P < 0.05 vs. sea level). Ventilatory response to hypercapnia was elevated at days 2–4 (P < 0.05 vs. sea level, 4.01 ± 2.98 vs. 2.09 ± 1.32 l min−1 mmHg−1). These findings indicate that: (1) the balance of arterial blood gases accounts for a large part of the observed variability (∼40%) leading to changes in CBF at high altitude; (2) cerebrovascular reactivity to hypercapnia and hypocapnia is differentially affected by high-altitude exposure and remains distorted during partial acclimatisation, and (3) alterations in cerebrovascular reactivity to CO2 may also affect ventilatory sensitivity.

How far is arterial spin labeling MRI from a clinical reality? Insights from arterial spin labeling comparative studies in Alzheimer's disease and other neurological disorders.

Aim: The risk of developing mild cognitive impairment (MCI) increases with type 2 diabetes (T2DM). Brain morphometric changes associated with MCI have been described. However Cerebral Blood Flow (CBF) changes in relation to MCI has not been fully investigated. This study aims to investigate regional CBF changes in subjects with T2DM and MCI. Method: Seventy-four age and gender matched subjects [28, T2DM (T2DM); 17, T2DM+MCI (T2DM/MCI) and 29, healthy volunteers (HV)] were recruited. All subjects underwent clinical and questionnaire (Addenbrooke’s Cognitive Assessment [ACE-R]) assessment along with Arterial Spin Labelling (ASL) perfusion Magnetic Resonance Imaging (MRI) of the brain. The ASL data was modelled to yield quantitative arterial CBF maps in neuroanatomical regions involved with cognitive function. Results: Demographic data revealed aged-matched participants between all three groups (mean age 69.3-71.5 years, ANOVA, p = 0.164). Mean age of last education was significantly lower in the T2DM/MCI group (mean±SD;15.1 ±0.9 when compared to the other groups (HV 19.3±5.6, T2DM 17.1±2.9) Kruskal-Wallis, p=0.003. T2DM/MCI ACE-R score (mean±SD; 83±4) was significantly lower compared to other groups (HV=96±2, T2DM=94±3; ANOVA p&amp;lt;0.001). There was significantly lower CBF in T2DM/MCI compared to T2DM and HV in the medial temporal lobes (CBF 76.8 ml/100g/min, ANOVA p&amp;lt;0.05), insula (CBF 67.5 ml/100g/min ANOVA p&amp;lt;0.005), and frontal lobes (CBF 71.8 ml/100g/min, ANOVA p&amp;lt;0.005)&amp;lt;bold&amp;gt;. &amp;lt;/bold&amp;gt;Pearson’s correlation revealed significant correlations between ACE-R score and regional CBF measurements in the medial temporal lobes, (p&amp;lt;0.05, r=.25) thalamus (p&amp;lt;0.05, r=.23) and insula (p&amp;lt;0.05, r=.29). Conclusion: This study demonstrates significantly lower CBF in T2DM MCI subjects in neuroanatomical regions responsible for cognitive function. This may be essential to help understand the pathological mechanisms that occur behind the increased risk of developing cognitive impairment in T2DM. Disclosure L. Hunt: None. D. Selvarajah: None. S. Tesfaye: Speaker's Bureau; Self; Pfizer Inc.. Other Relationship; Self; Janssen Pharmaceuticals, Inc., Takeda Development Centre Europe Ltd.. Advisory Panel; Self; Wörwag Pharma GmbH &amp; Co. KG. I.D. Wilkinson: None.

Cerebral haemodynamics, cognition and brain volumes in patients with type 2 diabetes

To investigate the relationship between changes in cerebral blood flow (CBF) and gray matter (GM) microstructure in Alzheimer's disease (AD) and mild cognitive impairment (MCI). A recruited cohort of 23 AD patients, 40 MCI patients, and 37 normal controls (NCs) underwent diffusional kurtosis imaging (DKI) for microstructure evaluation and pseudo-continuous arterial spin labeling (pCASL) for CBF assessment. We investigated the differences in diffusion- and perfusion-related parameters across the three groups, including CBF, mean diffusivity (MD), mean kurtosis (MK), and fractional anisotropy (FA). These quantitative parameters were compared using volume-based analyses for the deep GM and surface-based analyses for the cortical GM. The correlation between CBF, diffusion parameters, and cognitive scores was assessed using Spearman coefficients, respectively. The diagnostic performance of different parameters was investigated with k-nearest neighbor (KNN) analysis, using fivefold cross-validation to generate the mean accuracy (mAcc), mean precision (mPre), and mean area under the curve (mAuc). In the cortical GM, CBF reduction primarily occurred in the parietal and temporal lobes. Microstructural abnormalities were predominantly noted in the parietal, temporal, and frontal lobes. In the deep GM, more regions showed DKI and CBF parametric changes at the MCI stage. MD showed most of the significant abnormalities among all the DKI metrics. The MD, FA, MK, and CBF values of many GM regions were significantly correlated with cognitive scores. In the whole sample, the MD, FA, and MK were associated with CBF in most evaluated regions, with lower CBF values associated with higher MD, lower FA, or lower MK values in the left occipital lobe, left frontal lobe, and right parietal lobe. CBF values performed best (mAuc = 0.876) for distinguishing the MCI from the NC group. Last, MD values performed best (mAuc = 0.939) for distinguishing the AD from the NC group. Gray matter microstructure and CBF are closely related in AD. Increased MD, decreased FA, and MK are accompanied by decreased blood perfusion throughout the AD course. Furthermore, CBF values are valuable for the predictive diagnosis of MCI and AD. GM microstructural changes are promising as novel neuroimaging biomarkers of AD.

Background and Aims: In patients with severe cerebral small vessel disease (SVD), in whom both cerebral blood flow and cerebral autoregulation are reduced, intensive BP lowering might reduce cerebral blood flow (CBF) and increase the rate of white matter hyperintensity (WMH) progression. In an RCT we determined the effect of intensive BP lowering on CBF in lacunar stroke with confluent WMH. Method: In the PRESERVE trial Perfusion sub-study, patients from 2 sites with MRI confirmed symptomatic lacunar infarct and confluent WMH were randomised to “normal” (systolic=130-140mmHg, N=33) versus “intensive” (systolic=&lt;125mmHg, N=29) BP targets. CBF was determined using arterial spin labelling; the primary end point was change in global CBF between baseline and 3 months. Linear regression was performed comparing change in CBF against change in BP. Analyses controlled for site. Results: Mean(SD) systolic BP reduced by 8(12) and 27(17)mmHg in the standard/intensive groups, respectively (difference between groups p &lt;0.001) with achieved BP of 141(13) and 126(10) mmHg respectively. Baseline global CBF was 32(10) and 31(10)ml/min/100g in the standard/intensive groups. There was no difference in change in global CBF between treatment arms: standard, mean(SD) (ml/min/100g)= -0.46 (9.39); intensive, 0.73 (8.62), p =0.63. No differences were observed when analysis examined grey or white matter only, or was confined to those achieving target BP. Change in CBF did not have a significant association with change in systolic or diastolic BP. Conclusion: Intensive BP lowering did not reduce CBF in severe SVD characterised by lacunar stroke and confluent WMH. This suggests intensive CBF reduction is unlikely to accelerate WMH progression.

Reduced perfusion in white matter lesions in multiple sclerosis

Higher diastolic blood pressure aged 40‐44 is associated with declining cognition and increasing white matter lesions over 8‐12 year follow up.

Mild cognitive impairment (MCI) is a prodromal phase of dementia and is considered an important period for intervention to prevent conversion to dementia. It has been well established that multicomponent day-care programs including exercise training, cognitive intervention and music therapy have beneficial effects on cognition, but the effects on cerebral blood flow (CBF) in MCI remain unknown. This study examined whether a multicomponent day-care program would have beneficial effects on the longitudinal changes of CBF in MCI patients. Participants were 24 patients with MCI attending a day-care program; they underwent two 99 mTc-ethyl cysteinate dimer single photon emission computed tomography scans during the study period. We evaluated the association between the changes of regional cerebral blood flow and the attendance rate. There was a significant negative correlation between the reduction of regional CBF in the right parietal region and the attendance rate. We found no significant relation between the baseline CBF images and the attendance rate. Our results suggest that continuous participation in a multicomponent day-care program might prevent reduction in brain activity in patients with MCI.

Reports on the relative importance of the diastolic and systolic blood pressures (DBP and SBP) in age-related cognitive decline are mixed. Investigating the relation between DBP/SBP and functional and structural brain changes could elucidate which of the 2 measures is more critically important for brain function and, consequently, cognitive impairment. We investigated the association of SBP and DBP with cortical volume, cerebral blood flow (CBF), and white matter lesions (WML), in nondemented older adults with and without mild cognitive impairment (MCI; N = 265, 185 MCI, mean age = 64 years). Brachial blood pressure was measured twice while seated, and the average of the 2 measures was used. Cortical volume, gray matter (GM) CBF, and WML were estimated using T1-weighted imaging, arterial spin labeling, and fluid attenuation inversion recovery, respectively. Reduced cortical volume was associated with elevated DBP (β= -0.18, P = 0.034) but not with SBP (β = -0.10, P = 0.206). GM CBF was associated with DBP (β = -0.13, P = 0.048) but not with SBP (β = -0.07, P = 0.275). Likewise, CBF within brain regions where MCI patients showed hypoperfusion were only associated with DBP (DBP: β = -0.17, P = 0.005; SBP: β = -0.09, P = 0.120). WML volume was associated with both DBP (β = 0.20, P = 0.005) and SBP (β = 0.30, P < 0.001). For all measures, there was no interaction between DBP/SBP and cognitive status, indicating that these associations were independent of the cognitive status. Independently of the cognitive status, DBP is more critically important for GM volume and perfusion, whereas WML is associated with both blood pressures, likely reflecting long-term effect of hypertension and autoregulation dysfunction.