Alzheimer's disease (AD) is associated with severe cognitive impairments as well as some metabolic defects. Scant studies in animal models indicate a link between probiotics and cognitive function. This randomized, double-blind and controlled clinical trial was conducted among 60 AD patients to assess the effects of probiotic supplementation on cognitive function and metabolic status. The patients were randomly divided into two groups (n=30 in each group) treating with either milk (control group) or a mixture of probiotic (probiotic group). The probiotic supplemented group took 200 ml/day probiotic milk containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum and Lactobacillus fermentum (2×109 CFU/g for each) for 12 weeks. Mini-mental state examination (MMSE) score was recorded in all subjects before and after the treatment. Pre- and post-treatment fasting blood samples were obtained to determine the related markers. After 12 weeks intervention, compared with the control group (-5.03%±3.00), the probiotic treated (+27.90%±8.07) patients showed a significant improvement in the MMSE score (P<0.001). In addition, changes in plasma malondialdehyde (-22.01%±4.84 vs. +2.67%±3.86 µmol/L, P<0.001), serum high-sensitivity C-reactive protein (-17.61%±3.70 vs. +45.26%±3.50 µg/mL, P<0.001), homeostasis model of assessment-estimated insulin resistance (+28.84%±13.34 vs.+76.95%±24.60, P=0.002), Beta cell function (+3.45%±10.91 vs. +75.62%±23.18, P=0.001), serum triglycerides (-20.29%±4.49 vs. -0.16%±5.24 mg/dL, P=0.003) and quantitative insulin sensitivity check index (-1.83±1.26 vs. -4.66±1.70, P=0.006) in the probiotic group were significantly varied compared to the control group. We found that the probiotic treatment had no considerable effect on other biomarkers of oxidative stress and inflammation, fasting plasma glucose and other lipid profiles. Overall, the current study demonstrated that probiotic consumption for 12 weeks positively affects cognitive function and some metabolic statuses in the AD patients.

The widely spanning sensory cortex receives inputs from the disproportionately smaller nucleus of the thalamus, which results in a wide variety of travelling distance among thalamic afferents. Yet, latency from the thalamus to a cortical cell is remarkably constant across the cortex (typically, ≈2 ms). Here, we found a mechanism that produces invariability of latency among thalamocortical afferents, irrespective of the variability of travelling distances. The conduction velocity (CV) was calculated from excitatory postsynaptic currents recorded from layer IV cells in mouse thalamocortical slices by stimulating the ventrobasal nucleus of the thalamus (VB) and white matter (WM). In adults, the obtained CV for VB to WM (CV _VB-WM ; 3.28 ± 0.11 m/s) was ≈10 times faster than that of WM to layer IV cells (CV _WM-IV ; 0.33 ± 0.05 m/s). The CV _VB-WM was confirmed by recording antidromic single-unit responses from VB cells by stimulating WM. Exclusion of synaptic delay from CV _WM-IV did not account for the 10-fold difference of CV. By histochemical staining, it was revealed that VB to WM was heavily myelinated, whereas in the cortex staining became substantially weaker. We also found that such morphological and physiological characteristics developed in parallel and were accomplished around postnatal week 4. Considering that VB to WM is longer and more variable in length among afferents than is the intracortical region, such an enormous difference of CV makes conduction time heavily dependent on the length of intracortical region, which is relatively constant. Our finding may well provide a general strategy of connecting multiple sites irrespective of distances in the brain.

Alzheimer's disease (AD) is associated with cognitive dysfunction. Evidence indicates that gut microbiota is altered in the AD and, hence, modifying the gut flora may affect the disease. In the previous clinical research we evaluated the effect of a probiotic combination on the cognitive abilities of AD patients. Since, in addition to pathological disorders, the AD is associated with changes in oxidant/antioxidant and inflammatory/anti-inflammatory biomarkers, the present work was designed to evaluate responsiveness of the inflammatory and oxidative biomarkers to the probiotic treatment. The control (CON) and probiotic (PRO) AD patients were treated for 12 weeks by the placebo and probiotic supplementation, respectively. The patients were cognitively assessed by Test Your Memory (TYM = 50 scores). Also serum concentrations of nitric oxide (NO), glutathione (GSH), total antioxidant capacity (TAC), malondialdehyde (MDA), 8-hydroxy-2′ -deoxyguanosine (8-OHdG) and cytokines (TNF-a, IL-6, and IL-10) were measured. The cognitive test and the serum biomarkers were assessed pre- and post-treatment. According to TYM test 83.5% of the patients showed severe AD. The CON (12.86% ± 8.33) and PRO (−9.35% ± 16.83) groups not differently scored the cognitive test. Not pronounced change percent was found in the serum level of TNF-α (1.67% ± 1.33 vs. −0.15% ± 0.27), IL-6 (0.35% ± 0.17 vs. 2.18% ± 0.15), IL-10 (0.05% ± 0.10 vs. −0.70% ± 0.73), TAC (0.07% ± 0.07 and −0.06% ± 0.03), GSH (0.08% ± 0.05 and 0.04% ± 0.03) NO (0.11% ± 0.06 and 0.05% ± 0.09), MDA (−0.11% ± 0.03 and −0.17% ± 0.03), 8-OHdG (43.25% ± 3.01 and 42.70% ± 3.27) in the CON and PRO groups, respectively. We concluded that the cognitive and biochemical indications in the patients with severe AD are insensitive to the probiotic supplementation. Therefore, in addition to formulation and dosage of probiotic bacteria, severity of disease and time of administration deeply affects results of treatment.