The effects on cognitive functions of a movement-based intervention in patients with Alzheimer's type dementia: a pilot study.

OBJECTIVE: To explore the effect of a non-aerobic movement based activity on cognition in people with Alzheimer's type dementia (AD). METHODS: The sample consisted of 27 patients fulfilling the AD ICD-10 diagnostic criteria. The patient sample was randomly divided into two groups: The Exercise Group received 6 weeks movement training and comprised 15 participants with a mean age of 70.5 years (SD: 8). Control Group participated in a standard care group, which served as a control intervention, and consisted of 12 patients with an average age of 75.7 years (SD: 6.90). Cognitive functions were assessed using six computerised tests from the CANTAB, pre and post training. Data were analysed using t-tests. The false discovery rate (FDR) for multiple comparisons as well as Cohen's d effect size was used to assess the significant effects. RESULTS: Significant improvements in sustained attention, visual memory and a trend in working memory were found in the Exercise Group compared to Control Group after the 6 weeks training. In addition, after 6 weeks the Control Group deteriorated significantly in attention, while the AD patients who undertook the physical exercise showed a discrete improvement. CONCLUSIONS: The present study shows that a short course of non-aerobic movement based exercise is already effective at least in some aspects of cognitive functioning in patients with AD. Although the present study is a pilot study with small samples, nevertheless, the results are promising for the further investigation and development of non-aerobic movement programmes.

Separating the brain regions involved in recollection and familiarity in recognition memory.

The neural substrates of recognition memory retrieval were examined in a functional magnetic resonance imaging study designed to separate activity related to recollection from that related to continuous variations in familiarity. Across a variety of brain regions, the neural signature of recollection was found to be distinct from familiarity, demonstrating that recollection cannot be attributed to familiarity strength. In the prefrontal cortex, an anterior medial region was related to recollection, but lateral regions, including the anterior and dorsolateral prefrontal cortex, were related to familiarity. Along the lateral parietal cortex, two functionally distinct regions were also observed: a lateral parietal/temporal region related to recollection and a more superior parietal region involved in familiarity. Similarly, in medial parietal regions, the posterior cingulate was related to recollection, whereas the precuneus was related to familiarity. The hippocampus was related to recollection, but also exhibited an inverse relationship to familiarity-driven recognition confidence. The results indicate that recollection and familiarity rely on different networks of brain regions and provide insights into the functional roles of different regions involved in episodic recognition memory.

Cyclooxygenase inhibition attenuates endotoxin-induced spatial learning deficits, but not an endotoxin-induced blockade of long-term potentiation.

Peripheral administration of lipopolysaccharide (LPS), a potent bacterial endotoxin, can cause a variety of central effects, including production of cytokines and cyclooxygenases in the brain, as well as peripheral increases in corticosterone. These, in turn, may contribute to neuroimmune-induced neurocognitive deficits. We show here LPS causes deficits in hippocampal-dependent spatial learning in the water maze but that treatment with ibuprofen, a broad-spectrum cyclooxygenase inhibitor, reverses the deficits induced in spatial learning by LPS. We also show that LPS causes an impairment in the induction of long-term potentiation in the dentate gyrus in vivo, a major contemporary model of learning and memory. No differences were found in corticosterone levels in trunk blood but we find a decrease in brain-derived neurotrophic factor (BDNF) expression in LPS group compared to saline controls. Paradoxically compared to the behavioral findings treatment with ibuprofen does not attenuate the LPS-induced impairment in LTP or BDNF concentration in tetanized tissue.

Deficits in spatial learning and synaptic plasticity induced by the rapid and competitive broad-spectrum cyclooxygenase inhibitor ibuprofen are reversed by increasing endogenous brain-derived neurotrophic factor.

Cyclooxygenase (COX), which is present in two isoforms (COX1 and 2), synthesizes prostaglandins from arachidonic acid; it plays a crucial role in inflammation in both central and peripheral tissues. Here, we describe its role in synaptic plasticity and spatial learning in vivo via an effect on brain-derived neurotrophic factor (BDNF) and prostaglandin E2 (PGE2; both measured by Elisa). We found that broad-spectrum COX inhibition (BSCI) inhibits the induction of long-term potentiation (LTP; the major contemporary model of synaptic plasticity), and causes substantial and sustained deficits in spatial learning in the watermaze. Increases in BDNF and PGE2 following spatial learning and LTP were also blocked. Importantly, 4 days of prior exercise in a running wheel increased endogenous BDNF levels sufficiently to reverse the BSCI of LTP and spatial learning, and restored a parallel increase in LTP and learning-related BDNF and PGE2. In control experiments, we found that BSCI had no effect on baseline synaptic transmission or on the nonhippocampal visible-platform task; there was no evidence of gastric ulceration from BSCI. COX2 is inhibited by glucorticoids; there was no difference in blood corticosterone levels as measured by radioimmunoassay in any condition. Thus, COX plays a previously undescribed, permissive role in synaptic plasticity and spatial learning via a BDNF-associated mechanism.