Effect of combined GLP-1 analogue and bupropion/naltrexone on weight loss: a retrospective cohort study.

OBJECTIVE: Little is known about the effect of a multi-drug weight loss strategy in obesity treatment, particularly combining bupropion/naltrexone and glucagon-like peptide 1 (GLP-1) analogue. The purpose of this study was to evaluate if there are any additive effects of prescribing bupropion/naltrexone on top of GLP-1 analogue as weight loss therapy. METHODS: This was a retrospective cohort study of adult patients with a body mass index (BMI) ≥ 30 kg/m2 prescribed GLP-1 analogue therapy at an obesity specialist clinic in Vancouver, Canada. We compared a 6 and 12-month change in total body weight loss (TBWL) for those receiving monotherapy from the initiation of GLP-1 analogue therapy with those receiving combination therapy from the initiation of bupropion/naltrexone added-on therapy. Patients prescribed combination therapy were stratified into responder (loss of ≥ 5% TBWL) and non-responder (TBWL < 5%) subgroups based on initial response to the GLP-1 analogue alone for any amount of time. RESULTS: The mean weight loss among patients prescribed GLP-1 analogue monotherapy at 12 months was 11.42 kg, SD 9.95 (9.6% TBWL). There was no significant difference between these two treatment strategies overall (HR 0.88, 95% CI 0.68 to 1.14, p = 0.35). However, when stratified by response to initial GLP analogue therapy, the addition of bupropion/naltrexone was associated with a statistically significant reduction in weight in both the responder (4.3% TBWL (p < 0.01)) and non-responder groups (4.0% TBWL (p < 0.01)). CONCLUSIONS: GLP-1 analogues are an effective treatment for weight loss, and the addition of bupropion/naltrexone is associated with greater weight loss including in patients who are initially non-responsive to GLP-1 analogues.

Plasma ß-Amyloid in Mild Behavioural Impairment - Neuropsychiatric Symptoms on the Alzheimer's Continuum.

INTRODUCTION: Simple markers are required to recognize older adults at higher risk for neurodegenerative disease. Mild behavioural impairment (MBI) and plasma ß-amyloid (Aß) have been independently implicated in the development of incident cognitive decline and dementia. Here we studied the associations between MBI and plasma Aß42/Aß40. METHODS: Participants with normal cognition (n = 86) or mild cognitive impairment (n = 53) were selected from the Alzheimer's Disease Neuroimaging Initiative. MBI scores were derived from Neuropsychiatric Inventory items. Plasma Aß42/Aß40 ratios were assayed using mass spectrometry. Linear regressions were fitted to assess the association between MBI total score as well as MBI domain scores with plasma Aß42/Aß40. RESULTS: Lower plasma Aß42/Aß40 was associated with higher MBI total score (p = 0.04) and greater affective dysregulation (p = 0.04), but not with impaired drive/motivation (p = 0.095) or impulse dyscontrol (p = 0.29) MBI domains. CONCLUSION: In persons with normal cognition or mild cognitive impairment, MBI was associated with low plasma Aß42/Aß40. Incorporating MBI into case detection may help capture preclinical and prodromal Alzheimer's disease.

Tau-PET in early cortical Alzheimer brain regions in relation to mild behavioral impairment in older adults with either normal cognition or mild cognitive impairment.

Mild Behavioral Impairment (MBI) leverages later-life emergent and persistent neuropsychiatric symptoms (NPS) to identify a high-risk group for incident dementia. Phosphorylated tau (p-tau) is a hallmark biological manifestation of Alzheimer disease (AD). We investigated associations between MBI and tau accumulation in early-stage AD cortical regions. In 442 Alzheimer's Disease Neuroimaging Initiative participants with normal cognition or mild cognitive impairment, MBI status was determined alongside corresponding p-tau and Aß. Two meta-regions of interest were generated to represent Braak I and III neuropathological stages. Multivariable linear regression modelled the association between MBI as independent variable and tau tracer uptake as dependent variable. Among Aß positive individuals, MBI was associated with tau uptake in Braak I (ß=0.45(0.15), p<.01) and Braak III (ß=0.24(0.07), p<.01) regions. In Aß negative individuals, MBI was not associated with tau in the Braak I region (p=0.11) with a negative association in Braak III (p=.01). These findings suggest MBI may be a sequela of neurodegeneration, and can be implemented as a cost-effective framework to help improve screening efficiency for AD.

Tau-PET in early cortical Alzheimer brain regions in relation to mild behavioral impairment in older adults with either normal cognition or mild cognitive impairment.

Mild Behavioral Impairment (MBI) leverages later-life emergent and persistent neuropsychiatric symptoms (NPS) to identify a high-risk group for incident dementia. Phosphorylated tau (p-tau) is a hallmark biological manifestation of Alzheimer disease (AD). We investigated associations between MBI and tau accumulation in early-stage AD cortical regions. In 442 Alzheimer's Disease Neuroimaging Initiative participants with normal cognition or mild cognitive impairment, MBI status was determined alongside corresponding p-tau and Aß. Two meta-regions of interest were generated to represent Braak I and III neuropathological stages. Multivariable linear regression modelled the association between MBI as independent variable and tau tracer uptake as dependent variable. Among Aß positive individuals, MBI was associated with tau uptake in Braak I (ß =0.45(0.15), p<.01) and Braak III (ß =0.24(0.07), p<.01) regions. In Aß negative individuals, MBI was not associated with tau in the Braak I region (p=.11) with a negative association in Braak III (p=.01). These findings suggest MBI may be a sequela of neurodegeneration, and can be implemented as a cost-effective framework to help improve screening efficiency for AD.

Plasma Neurofilament Light: A Marker of Neurodegeneration in Mild Behavioral Impairment.

BACKGROUND: Assessing neuropsychiatric symptoms (NPS) in older adults is important for determining dementia risk. Mild behavioral impairment (MBI) is an at-risk state for cognitive decline and dementia, characterized by emergent NPS in later life. MBI has significantly higher dementia incidence than late life psychiatric conditions. However, its utility as a proxy for neurodegeneration has not been demonstrated. Plasma neurofilament light (NfL) is a validated biomarker of axonal damage, and has been shown to associate with hallmarks of neurodegeneration. OBJECTIVE: The purpose of this investigation was to identify associations between NfL rate of change and the presence of MBI symptomatology. METHODS: We evaluated the association of MBI with changes in NfL in a cohort (n = 584; MBI + n = 190, MBI- n = 394) of non-demented participants from the Alzheimer's Disease Neuroimaging Initiative. MBI was determined by transforming Neuropsychiatric Inventory Questionnaire items using a published algorithm. Change in NfL was calculated over 2 years. RESULTS: Time*MBI status was the only significant interaction to predict change in NfL concentrations (F(1,574) = 4.59, p = 0.032), even after controlling for age, mild cognitive impairment, and demographics. Analyses reclassifying 64 participants with new onset MBI over 2 years similarly demonstrated greater increases in NfL (F(1,574) = 5.82, p = 0.016). CONCLUSION: These findings suggest MBI is a clinical proxy of early phase neurodegeneration with putative utility in identifying those at dementia risk. MBI can be used as a case ascertainment approach to capture those at high risk for cognitive decline and dementia, and is an important construct for clinicians dealing with cognitive and neuropsychiatric symptomatology in older adults.