Background: Studies of physical exercise in patients with Alzheimer’s disease (AD) are few and results have been inconsistent. Objective: To assess the effects of a moderate-to-high intensity aerobic exercise program in patients with mild AD. Methods: In a randomized controlled trial, we recruited 200 patients with mild AD to a supervised exercise group (60-min sessions three times a week for 16 weeks) or to a control group. Primary outcome was changed from baseline in cognitive performance estimated by Symbol Digit Modalities Test (SDMT) in the intention-to-treat (ITT) group. Secondary outcomes included changes in quality of life, ability to perform activities of daily living, and in neuropsychiatric and depressive symptoms. Results: The ITT analysis showed no significant differences between intervention and control groups in change from baseline of SDMT, other cognitive tests, quality of life, or activities of daily living. The change from baseline in Neuropsychiatric Inventory differed significantly in favor of the intervention group (mean: –3.5, 95% confidence interval (CI) –5.8 to –1.3, p = 0.002). In subjects who adhered to the protocol, we found a significant effect on change from baseline in SDMT as compared with the control group (mean: 4.2, 95% CI 0.5 to 7.9, p = 0.028), suggesting a dose-response relationship between exercise and cognition. Conclusions: This is the first randomized controlled trial with supervised moderate-to-high intensity exercise in patients with mild AD. Exercise reduced neuropsychiatric symptoms in patients with mild AD, with possible additional benefits of preserved cognition in a subgroup of patients exercising with high attendance and intensity.

Improvements in attentional performance are at the core of proposed mechanisms for stress reduction in mindfulness meditation practices. However, this claim can be questioned because no previous studies have actively manipulated test effort in control groups and controlled for effects of stress reduction per se. In a blinded design, 48 young, healthy meditation novices were randomly assigned to a mindfulness-based stress reduction (MBSR), nonmindfulness stress reduction (NMSR), or inactive control group. At posttest, inactive controls were randomly split into nonincentive and incentive controls, the latter receiving a financial reward to improve attentional performance. Pre- and postintervention, 5 validated attention paradigms were employed along with self-report scales on mindfulness and perceived stress and saliva cortisol samples to measure physiological stress. Attentional effects of MBSR, NMSR, and the financial incentive were comparable or significantly larger in the incentive group on all reaction-time-based measures. However, selective attention in the MBSR group improved significantly more than in any other group. Similarly, only the MBSR intervention improved the threshold for conscious perception and visual working memory capacity. Furthermore, stress-reducing effects of MBSR were supported because those in the MBSR group showed significantly less perceived and physiological stress while increasing their mindfulness levels significantly. We argue that MBSR may contribute uniquely to attentional improvements but that further research focusing on non-reaction-time-based measures and outcomes less confounded by test effort is needed. Critically, our data demonstrate that previously observed improvements of attention after MBSR may be seriously confounded by test effort and nonmindfulness stress reduction.

Cerebral blood flow (CBF) and cerebral metabolic rate are normally coupled, that is an increase in metabolic demand will lead to an increase in flow. However, during functional activation, CBF and glucose metabolism remain coupled as they increase in proportion, whereas oxygen metabolism only increases to a minor degree—the so-called uncoupling of CBF and oxidative metabolism. Several studies have dealt with these issues, and theories have been forwarded regarding the underlying mechanisms. Some reports have speculated about the existence of a potentially deficient oxygen supply to the tissue most distant from the capillaries, whereas other studies point to a shift toward a higher degree of non-oxidative glucose consumption during activation. In this review, we argue that the key mechanism responsible for the regional CBF (rCBF) increase during functional activation is a tight coupling between rCBF and glucose metabolism. We assert that uncoupling of rCBF and oxidative metabolism is a consequence of a less pronounced increase in oxygen consumption. On the basis of earlier studies, we take into consideration the functional recruitment of capillaries and attempt to accommodate the cerebral tissue's increased demand for glucose supply during neural activation with recent evidence supporting a key function for astrocytes in rCBF regulation.