The earliest and perhaps best example of an interaction between nutrition and dementia is related to thiamine (vitamin B1). Throughout the last century, research showed that thiamine deficiency is associated with neurological problems, including cognitive deficits and encephalopathy. Multiple similarities exist between classical thiamine deficiency and Alzheimer’s disease (AD) in that both are associated with cognitive deficits and reductions in brain glucose metabolism. Thiamine-dependent enzymes are critical components of glucose metabolism that are reduced in the brains of AD patients and by thiamine deficiency, and their decline could account for the reduction in glucose metabolism. In preclinical models, reduced thiamine can drive AD-like abnormalities, including memory deficits, plaques, and hyperphosphorylation of tau. Furthermore, excess thiamine diminishes AD-like pathologies. In addition to dietary deficits, drugs, or other manipulations that interfere with thiamine absorption can cause thiamine deficiency. Elucidating the reasons why the brains of AD patients are functionally thiamine deficient and determining the effects of thiamine restoration may provide critical information to help treat patients with AD.

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Reduced glucose metabolism is an invariant feature of Alzheimer’s Disease (AD) and an outstanding biomarker of disease progression. Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional glucose hypometabolism remains unclear. Thiamine-dependent processes are critical in glucose metabolism and are diminished in brains of AD patients at autopsy. Further, the reductions in thiamine-dependent processes are highly correlated to the decline in clinical dementia rating scales. In animal models, thiamine deficiency exacerbates plaque formation, promotes phosphorylation of tau and impairs memory. In contrast, treatment of mouse models of AD with the thiamine derivative benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses memory deficits. Diabetes predisposes to AD, which suggests they may share some common mechanisms. Benfotiamine diminishes peripheral neuropathy in diabetic humans and animals. In diabetes, benfotiamine induces key thiamine-dependent enzymes of the pentose shunt to reduce accumulation of toxic metabolites including advanced glycation end products (AGE). Related mechanisms may lead to reversal of plaque formation by benfotiamine in animals. If so, the use of benfotiamine could provide a safe intervention to reverse biological and clinical processes of AD progression.

Combined tDCS and robotic training is a safe and feasible procedure in subacute stroke patients. However, adding tDCS to robot-assisted gait training shows no benefit over robotic gait training alone.

Apathy and hypersomnia occur after stroke and, by definition, reduce participation in rehabilitation, but their effect on outcome from acute rehabilitation is not known. We performed a retrospective review of 213 patients admitted to a stroke-specialized acute rehabilitation unit in the United States. All patients had ischemic or hemorrhagic stroke, and no dementia or dependence on others pre-stroke. We diagnosed apathy and hypersomnia using standardized documentation by treating therapists. We used multiple regression analysis to control for overall impairment (combination of strength, cognitive and sensory measures), age, time since stroke, and stroke type (ischemic or hemorrhagic). 44 (21%) of patients had persistent apathy, and 12 (5.6%) had persistent hypersomnia. Both groups were more impaired in cognition, sustained attention, and more likely to be treated for depression. Patients with apathy were 2.4 times more likely to go to a nursing home, and had discharge FIM scores 12 points below the mean. Patients with hypersomnia were 10 times more likely to go to a nursing home, and had discharge FIM scores 16 points below the mean. These findings indicate that studies to prospectively define these clinical factors and potential confounds using standardized tools are indicated, and if confirmed, justify studies to identify these patients early and develop targeted interventions.

Corticomotor conduction and cortical topography were appreciably normal despite only liminal activation of the target muscle with voluntary effort. Muscles with these characteristics may benefit from a targeted rehabilitation program even in the chronic phase after SCI.

Classical de-afferentation studies, as well as experience-dependent visual plasticity paradigms, have confirmed that both the developing and adult nervous system are capable of unexpected levels of plasticity. This capacity is underscored by the significant spontaneous recovery that can occur in patients with mild-to-moderate impairment following stroke. An evolving model is that an interaction of biological and environmental factors during all epochs post-stroke influences the extent and quality of this plasticity. Here, we discuss data that have implicated specific epigenetic proteins as integrators of environmental influences in 3 aspects of stroke recovery: spontaneous impairment reduction in humans; peri-infarct rewiring in animals as a paradigm for developing therapeutically-driven impairment reduction beyond natural spontaneous recovery; and, finally, classical hippocampal learning and memory paradigms that are theoretically important in skill acquisition for both impairment reduction and compensatory strategies in the rehabilitation setting. Our discussion focuses primarily on B lymphoma Mo-MLV1 insertion region proteins of the polycomb repressive complex, alpha thalassemia/mental retardation syndrome X-linked chromatin remodeling factors, and the best known and most dynamic gene repressors, histone deacetylases. We will highlight exciting current data associated with these proteins and provide promising speculation about how they can be manipulated by drugs, biologics, or noninvasive stimulation for stroke recovery.