Cerebral autoregulation and baroreflex sensitivity are key mechanisms that maintain cerebral blood flow. This study assessed whether these control mechanisms are affected in patients with dementia and mild cognitive impairment due to Alzheimer disease, as this would increase the risks of antihypertensive treatment. We studied 53 patients with dementia (73.1 years [95% confidence interval (CI), 71.4-74.8]), 37 patients with mild cognitive impairment (69.2 years [95% CI, 66.4-72.0]), and 47 controls (69.4 years [95% CI, 68.3-70.5]). Beat-to-beat blood pressure (photoplethysmography), heart rate, and cerebral blood flow velocity (transcranial Doppler) were measured during 5-minute rest (sitting) and 5 minutes of orthostatic challenges, using repeated sit-to-stand maneuvers. Cerebral autoregulation was assessed using transfer function analysis and the autoregulatory index. Baroreflex sensitivity was estimated with transfer function analysis and by calculating the heart rate response to blood pressure changes during the orthostatic challenges. Dementia patients had the lowest cerebral blood flow velocity (=0.004). During rest, neither transfer function analysis nor the autoregulatory index indicated impairments in cerebral autoregulation. During the orthostatic challenges, higher autoregulatory index (=0.011) and lower transfer function gain (=0.017), indicating better cerebral autoregulation, were found in dementia (4.56 arb. unit [95% CI, 4.14-4.97]; 0.59 cm/s per mm Hg [95% CI, 0.51-0.66]) and mild cognitive impairment (4.59 arb. unit [95% CI, 4.04-5.13]; 0.51 cm/s per mm Hg [95% CI, 0.44-0.59]) compared with controls (3.71 arb. unit [95% CI, 3.35-4.07]; 0.67 cm/s per mm Hg [95% CI, 0.59-0.74]). Baroreflex sensitivity measures did not differ between groups. In conclusion, the key mechanisms to control blood pressure and cerebral blood flow are not reduced in 2 stages of Alzheimer disease compared with controls, both in rest and during orthostatic changes that reflect daily life challenges.

New Findings r What is the central question in this study?It is unknown to what extent increasing age influences the dynamic adaptations of cerebral blood flow velocity and cortical oxygenation in response to changes in blood pressure (cerebral autoregulation) and to changes in carbon dioxide (cerebrovascular CO 2 reactivity). r What is the main finding and its importance?We have shown that ageing up to 86 years is associated with an overall preservation of dynamic cerebral autoregulation and cerebrovascular CO 2 reactivity, leading to a sufficiency of cerebral cortical oxygenation during daily life activities, despite the decrease in absolute cerebral blood flow velocity and increase in cerebrovascular resistance with advancing age.With ageing, cerebral blood flow velocity (CBFV) decreases; however, to what extent dynamic cerebral autoregulation and cerebrovascular CO 2 reactivity are influenced by ageing is unknown. The aim was to examine the dynamic responses of CBFV and cortical oxygenation to changes in blood pressure (BP) and arterial CO 2 across different ages. Fifty-eight participants in three age groups were included, as follows: young (n = 20, 24 ± 2 years old), elderly (n = 20, 66 ± 1 years old), and older elderly (n = 18, 78 ± 3 years old). The CBFV was measured using transcranial Doppler ultrasound, simultaneously with oxyhaemoglobin (O 2 Hb) using near-infrared spectroscopy and beat-to-beat BP measurements using Finapres. Postural manoeuvres were performed to induce haemodynamic fluctuations. Cerebrovascular CO 2 reactivity was tested with hyperventilation and CO 2 inhalation. With age, CBFV decreased (young 59 ± 12 cm s −1 , elderly 48 ± 7 cm s −1 and older elderly 42 ± 9 cm s −1 , P < 0.05) and cerebrovascular resistance increased (1.46 ± 0.58, 1.81 ± 0.36 and 1.98 ± 0.52 mmHg cm −1 s −1 , respectively, P < 0.05). Normalized gain (autoregulatory damping) increased with age for BP-CBFV (0.88 ± 0.18, 1.31 ± 0.30 and 1.06 ± 0.34, respectively, P < 0.05) and CBFV-O 2 Hb (0.10 ± 0.09, 0.12 ± 0.04 and 0.17 ± 0.08, respectively, P < 0.05) during the repeated sit-stand manoeuvre at 0.05 Hz. Even though the absolute changes in CBFV and cerebrovascular resistance index during the cerebrovascular CO 2 reactivity were higher in the young group, the percentage changes in CBFV, cerebrovascular resistance index and O 2 Hb were similar in all age groups. In conclusion, there was no decline in dynamic cerebral autoregulation and cerebrovascular CO 2 reactivity with increasing age up to 86 years. Despite the decrease in cerebral blood flow * M. H. Oudegeest-Sander and A. H. E. A. van Beek contributed equally to this work.

Background: Physical activity is known to influence sleep efficiency. Relatively little is known about the relationship between physical activity and sleep efficiency in young and older humans and the impact of exercise training on sleep efficiency in healthy older individuals. Objectives: To determine the relationship between physical fitness and daily energy expenditure with sleep efficiency in young and older subjects, and assess the effect of 12-month exercise training on sleep efficiency in healthy older participants. Methods: The relationship between physical fitness (maximal cycling test) and daily energy expenditure (accelerometry) with sleep efficiency (accelerometry) was examined cross-sectionally in 12 healthy young adults (27 ± 5 years) and 21 healthy older participants (69 ± 3 years). Subsequently, the effect of 12-month exercise training (n = 11) or control period (n = 10) on sleep efficiency in older participants was examined using a randomized controlled trial. Results: Daily energy expenditure and sleep efficiency did not differ between young and older subjects. A significant correlation was found between energy expenditure and sleep efficiency (r = 0.627, p = 0.029) in young adults, but not in older participants (r = –0.158, p = 0.49). Physical fitness did not correlate with sleep efficiency in either group. Exercise training significantly improved physical fitness (15.0%, p < 0.001), but failed to alter sleep characteristics such as sleep efficiency, sleep onset latency and awakenings. Conclusions: We found that young adults with higher daily energy expenditure have greater sleep efficiency, whilst this relationship is diminished with advanced age. In contrast, we found no correlation between physical fitness and sleep characteristics in healthy young or older participants, which may explain the lack of improvement in sleep characteristics in older participants with 12-month exercise training. Exercise training may be more successful in subjects with existing sleep disturbancesto improve sleep characteristics rather than in healthy older subjects.

Aging leads to accumulation of irreversible advanced glycation end-products (AGEs), contributing to vascular stiffening and endothelial dysfunction. When combined with the AGE-crosslink breaker Alagebrium, exercise training reverses cardiovascular aging in experimental animals. This study is the first to examine the effect of Alagebrium, with and without exercise training, on endothelial function, arterial stiffness and cardiovascular risk in older individuals. Forty-eight non-exercising individuals (mean age 70±4 years) without manifest diseases or use of medication were allocated into 4 groups for a 1-year intervention: Exercise training & Alagebrium (200mg/day); Exercise training & placebo; No exercise training & Alagebrium (200mg/day); No exercise training & placebo. We performed a maximal exercise test (VO2max) and measured endothelial function using venous occlusion plethysmography and intra-arterial infusion of acetylcholine, sodium nitroprusside and NG-monomethyl-L-arginine. Arterial stiffness was measured using pulse wave velocity. Cardiovascular risk was calculated using the Lifetime Risk Score (LRS). In the exercise training groups, LRS and VO2max improved significantly (23.9±4.5 to 27.2±4.6mlO2/min/kg, p<0.001). Endothelial response to the vasoactive substances did not change, nor did arterial stiffness in any of the four groups. In conclusion, one year of exercise training significantly improved physical fitness and lifetime risk for cardiovascular disease without affecting endothelial function or arterial stiffness. The use of the AGE-crosslink breaker Alagebrium had no independent effect on vascular function, nor did it potentiate the effect of exercise training. Despite the clinical benefits of exercise training for older individuals, neither exercise training nor Alagebrium (alone or in combination) was able to reverse the vascular effects of decades of sedentary aging.

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