Twelve Weeks of Intermittent Caloric Restriction Diet Mitigates Neuroinflammation in Midlife Individuals with Multiple Sclerosis: A Pilot Study with Implications for Prevention of Alzheimer's Disease.

BACKGROUND: Multiple sclerosis (MS) is a prototype neuroinflammatory disorder with increasingly recognized role for neurodegeneration. Most first-line treatments cannot prevent the progression of neurodegeneration and the resultant disability. Interventions can improve symptoms of MS and might provide insights into the underlying pathology. OBJECTIVE: To investigate the effect of intermittent caloric restriction on neuroimaging markers of MS. METHODS: We randomized ten participants with relapsing remitting MS to either a 12-week intermittent calorie restriction (iCR) diet (n = 5) or control (n = 5). Cortical thickness and volumes were measured through FreeSurfer, cortical perfusion was measured by arterial spin labeling and neuroinflammation through diffusion basis spectrum imaging. RESULTS: After 12 weeks of iCR, brain volume increased in the left superior and inferior parietal gyri (p: 0.050 and 0.049, respectively) and the banks of the superior temporal sulcus (p: 0.01). Similarly in the iCR group, cortical thickness improved in the bilateral medial orbitofrontal gyri (p: 0.04 and 0.05 in right and left, respectively), the left superior temporal gyrus (p: 0.03), and the frontal pole (p: 0.008) among others. Cerebral perfusion decreased in the bilateral fusiform gyri (p: 0.047 and 0.02 in right and left, respectively) and increased in the bilateral deep anterior white matter (p: 0.03 and 0.013 in right and left, respectively). Neuroinflammation, demonstrated through hindered and restricted water fractions (HF and RF), decreased in the left optic tract (HF p: 0.02), and the right extreme capsule (RF p: 0.007 and HF p: 0.003). CONCLUSION: These pilot data suggest therapeutic effects of iCR in improving cortical volume and thickness and mitigating neuroinflammation in midlife adults with MS.

Diagnostic Accuracy of the SLU AMSAD Scale for Depression in Older Adults Without Dementia.

OBJECTIVES: To evaluate the diagnostic accuracy of a short depression screening tool, the Saint Louis University (SLU) AMSAD depression scale, relative to the Geriatric Depression Scale-15 (GDS-15) and Montgomery-Asberg Depression Rating Scale (MADRS), and in relation to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) criteria for major depressive disorder, in cognitively intact older adults. DESIGN: Cross-sectional. SETTING: Outpatient geriatric psychiatry clinic. PARTICIPANTS: Fifty older adults (aged ≥65 years) without dementia. MEASUREMENTS: GDS-15, MADRS, SLU AMSAD, and DSM-5 criteria for major depressive disorder were administered. RESULTS: Total scores (continuous variables) for the GDS-15, MADRS, and SLU AMSAD correlated significantly with the DMS-5 criteria for major depressive disorder (MDD) [area under the curve (AUC) ≥ 0.93, sensitivity = 0.93, and specificity ≥ 0.80]. Optimal cutoffs were 9+ for GDS-15, 18+ for MADRS, and 7+ for SLU AMSAD. When score results were categorized according to their known cutoffs for mild, moderate, and severe depression, AUC values were again high (range = 0.82-0.89), with adequate levels of sensitivity (0.87-0.93) and specificity (0.71-0.86), distinguishing no or mild depression from moderate or severe depression in relation to the DSM-5 diagnostic criteria for MDD. CONCLUSIONS AND IMPLICATIONS: Strong diagnostic accuracy was shown for the 3 scales. The SLU AMSAD performed as well as the GDS-15 and slightly better than the MADRS. The superiority of the SLU AMSAD is supported by the fact that it encompasses only 5 simply worded, simply scaled items to be used in busy clinical settings.

An update on the safety of current therapies for Alzheimer's disease: focus on rivastigmine.

Alzheimer's disease (AD) is the most common cause of major neurocognitive disorders worldwide. Despite all research efforts, therapeutic options for AD are still limited to two drug classes: cholinesterase inhibitors (ChEIs) and the NMDA-receptor antagonist memantine. Donepezil, rivastigmine and galantamine are the three ChEIs FDA-approved as first-line treatment for AD. Although they share the same mode of action, they differ in terms of their pharmacologic characteristics and route of administration, which can impact their safety and tolerability profile. Rivastigmine, available in both oral and transdermal patch formulations, is a slowly reversible dual inhibitor of acetyl and butyryl cholinesterase, selective for the G1 isoform of acetylcholinesterase, without hepatic metabolism by the CYP-450 system. Despite its unique features, it has been associated with a higher incidence of adverse events in comparison to other ChEIs. The oral form, approved for the treatment of mild to moderate AD, is associated with a higher incidence of gastrointestinal side effects. The transdermal patch formulation approved for use across all stages of AD has been shown to have a better tolerability profile in comparison to both the oral form and even other ChEIs. One important tolerability concern is adverse dermatologic reactions, which are mostly benign, and can be either preventable or manageable. One important safety concern is the risk of treatment overdose by administering multiple patches at the same time, potentially leading to fatal outcomes. This can be prevented by educating patients and caregivers about the proper use of the patch. The goal for the future would be to optimize the patch formulation to increase both efficacy and safety.