Clinical Overview of REM Sleep Behavior Disorder

AbstractRapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by loss of muscle atonia during REM sleep that allows motor responses to dream content. Patients display patterns of unusual, complex, and even violent motor activities. There is a high risk for harm to the patients or their bedpartners. REM sleep behavior disorder is more likely to occur in synucleinopathies such as Parkinson's disease, Lewy body dementia, and multiple system atrophy and may precede clinical manifestations by decades. In secondary RBD, brainstem centers involved in muscle atonia during REM are disrupted. These conditions include multiple sclerosis, cerebral vascular accidents, and brainstem tumors. The acute onset of RBD may associate with the use of antidepressants and acute withdrawal from alcohol. The diagnosis of RBD should be confirmed by polysomnography utilizing multiple-limb electromyography and synchronized digital video monitoring and demonstrate elevation of muscle tone during REM sleep along with dream enactment behavior. The differential diagnosis includes sleepwalking, nocturnal seizures, sleep apnea, and periodic limb movement disorder. Management focuses on maximizing safety, use of clonazepam/melatonin, and discussion of prognosis with patients

Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study

Introduction: Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It reduces pathology in transgenic models of Alzheimer's disease (AD) and is a promising candidate for treating human AD. The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD. Methods: We performed a 24-week randomized, double blind, placebo-controlled study of Curcumin C3 Complex® with an open-label extension to 48 weeks. Thirty-six persons with mild-to-moderate AD were randomized to receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. For weeks 24 through 48, subjects that were receiving curcumin continued with the same dose, while subjects previously receiving placebo were randomized in a 1:1 ratio to 2 grams/day or 4 grams/day. The primary outcome measures were incidence of adverse events, changes in clinical laboratory tests and the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at 24 weeks in those completing the study. Secondary outcome measures included the Neuropsychiatric Inventory (NPI), the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale, levels of Aβ1-40 and Aβ1-42 in plasma and levels of Aβ1-42, t-tau, p-tau181 and F2-isoprostanes in cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured. Results: Mean age of completers (n = 30) was 73.5 years and mean Mini-Mental Status Examination (MMSE) score was 22.5. One subject withdrew in the placebo (8%, worsened memory) and 5/24 subjects withdrew in the curcumin group (21%, 3 due to gastrointestinal symptoms). Curcumin C3 Complex® was associated with lowered hematocrit and increased glucose levels that were clinically insignificant. There were no differences between treatment groups in clinical or biomarker efficacy measures. The levels of native curcumin measured in plasma were low (7.32 ng/mL). Conclusions: Curcumin was generally well-tolerated although three subjects on curcumin withdrew due to gastrointestinal symptoms. We were unable to demonstrate clinical or biochemical evidence of efficacy of Curcumin C3 Complex® in AD in this 24-week placebo-controlled trial although preliminary data suggest limited bioavailability of this compound. Trial registration ClinicalTrials.gov Identifier: NCT00099710

Clinical Overview of REM Sleep Behavior Disorder.

AbstractRapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by loss of muscle atonia during REM sleep that allows motor responses to dream content. Patients display patterns of unusual, complex, and even violent motor activities. There is a high risk for harm to the patients or their bedpartners. REM sleep behavior disorder is more likely to occur in synucleinopathies such as Parkinson's disease, Lewy body dementia, and multiple system atrophy and may precede clinical manifestations by decades. In secondary RBD, brainstem centers involved in muscle atonia during REM are disrupted. These conditions include multiple sclerosis, cerebral vascular accidents, and brainstem tumors. The acute onset of RBD may associate with the use of antidepressants and acute withdrawal from alcohol. The diagnosis of RBD should be confirmed by polysomnography utilizing multiple-limb electromyography and synchronized digital video monitoring and demonstrate elevation of muscle tone during REM sleep along with dream enactment behavior. The differential diagnosis includes sleepwalking, nocturnal seizures, sleep apnea, and periodic limb movement disorder. Management focuses on maximizing safety, use of clonazepam/melatonin, and discussion of prognosis with patients

Quantitative MRI Differences Between Early versus Late Onset Alzheimer\u27s Disease.

Investigators report greater parietal tau deposition and alternate frontoparietal network involvement in early onset Alzheimer\u27s Disease (EOAD) with onset \u3c65 years as compared with typical late onset AD (LOAD). To determine whether clinical brain MRI volumes reflect these differences in EOAD compared with LOAD. This study investigated the clinical MRI scans of 45 persons with Clinically Probable AD with onset \u3c65 years, and compared them to 32 with Clinically Probable AD with onset ≥65 years. Brain volumes on their T1 MRI scans were quantified with a volumetric program. Receiver operating curve analyses were performed. Persons with EOAD had significantly smaller parietal lobes (volumetric percentiles) than LOAD. Late onset Alzheimer\u27s Disease had a smaller left putamen and hippocampus. Area Under the Curve was 96.5% with brain region delineation of EOAD compared to LOAD. This study indicates parietal atrophy less than 30% of normal on clinical MRI scans is suggestive of EOAD compared to LOAD

Brain Structure in Bilingual Compared to Monolingual Individuals with Alzheimer\u27s Disease: Proof of Concept.

BACKGROUND: Bilingualism is increasingly recognized as protective in persons at risk for Alzheimer\u27s disease (AD). OBJECTIVE: Compare MRI measured brain volumes in matched bilinguals versus monolinguals with AD. METHODS: This IRB approved study analyzed T1 volumetric brain MRIs of patients with criteria-supported Probable AD. We identified 17 sequential bilinguals (any native language) with Probable AD, matched to 28 (62%) monolinguals on age and MMSE. Brain volumes were quantified with Neuroreader. Regional volumes as fraction of total intracranial volume (TIV) were compared between both groups, and Cohen\u27s D effect sizes were calculated for statistically significant structures. Partial correlations between bilingualism and brain volumes adjusted for age, gender, and TIV. RESULTS: Bilinguals had higher brain volumes in 37 structures. Statistical significance (p \u3c 0.05) was observed in brainstem (t = 2.33, p = 0.02, Cohen\u27s D = 0.71) and ventral diencephalon (t = 3.01, p = 0.004, Cohen\u27s D = 0.91). Partial correlations showed statistical significance between bilingualism and larger volumes in brainstem (rp = 0 . 37, p = 0.01), thalamus (rp = 0.31, p = 0.04), ventral diencephalon (rp = 0.50, p = 0.001), and pallidum (rp = 0.38, p = 0.01). Bilingualism positively correlated with hippocampal volume, though not statistically significant (rp = 0.17, p = 0.26). No brain volumes were larger in monolinguals. CONCLUSION: Bilinguals demonstrated larger thalamic, ventral diencephalon, and brainstem volumes compared to matched monolinguals with AD. This may represent a neural substrate for increased cognitive reserve in bilingualism. Future studies should extrapolate this finding into cognitively normal persons at risk for AD

MRI Volumetric Quantification in Persons with a History of Traumatic Brain Injury and Cognitive Impairment.

BACKGROUND: While traumatic brain injury (TBI) is recognized as a risk factor for dementia, there is lack of clinical tools to identify brain changes that may confer such vulnerability. Brain MRI volumetric quantification can sensitively identify brain atrophy. OBJECTIVE: To characterize regional brain volume loss in persons with TBI presenting with cognitive impairment. METHODS: IRB approved review of medical records in patients with cognitive decline focused on those who had documented TBI histories and brain MRI scans after TBI (n = 40, 67.7±14.5 years) with volumetric quantification by applying an FDA cleared software program. TBI documentation included head trauma mechanism. Brain volumes were compared to a normative database to determine the extent of atrophy. Correlations between these regions and global tests of cognition (MMSE in n = 17, MoCA in n = 27, n = 14 in both) were performed. RESULTS: Multiple regions demonstrated volume loss in TBI, particularly ventral diencephalon, putamen, and pallidum with smaller magnitude of atrophy in temporal lobes and brainstem. Lobar structures showed strongest correlations between atrophy and lower scores on MMSE and MoCA. The hippocampus, while correlated to tests of cognitive function, was the least atrophic region as a function of TBI history. CONCLUSION: Persons with TBI history exhibit show regional brain atrophy. Several of these areas, such as thalamus and temporal lobes, also correlate with cognitive function. Alzheimer\u27s disease atrophy was less likely given relative sparing of the hippocampi. Volumetric quantification of brain MRI in TBI warrants further investigation to further determine its clinical potential in TBI and differentiating causes of cognitive impairment

ICARE AD-US: Design of a Prospective, Single-Arm, Multicenter, Noninterventional, Real-World Study of Aducanumab in the United States (P1-1.Virtual)

Abstract onl