| 1. |
- Kullenberg, Helena, et al.
(author)
-
Associations between the use of metformin and behavioral and psychological symptoms in patients with Alzheimer's disease, and type 2 diabetes mellitus : A register-based study
- 2023
-
In: Current Alzheimer Research. - 1567-2050 .- 1875-5828. ; 20:2, s. 109-119
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Metformin, the first-line anti-diabetic drug treatment in patients with type 2 diabetes mellitus (T2DM), is suggested to be anti-inflammatory, antioxidative, and improve cognitive function, making it a promising contribution to treating Alzheimer´s disease (AD). However, the effect of metformin on behavioral and psychological symptoms of dementia (BPSD) in patients with AD has not been explored.OBJECTIVE: To investigate the associations between metformin and BPSD in patients with AD and T2DM and explore possible interaction with other antidiabetic drugs.METHODS: This cross-sectional study was based on data from the Swedish BPSD register. A total of 3745 patients with AD and antidiabetic drug treatment were included. Associations and interactions between antidiabetic drugs and BPSD were investigated by binary logistic regression.RESULTS: The use of metformin was associated with lower odds for symptoms of depression (OR 0.77, CI (95%) 0.61-0.96, p = 0.022) and anxiety (OR 0.74, CI (95%) 0.58-0.94, p = 0.015) after adjustment for age, gender, specific diagnosis, and drugs. We could not demonstrate this association with another antidiabetic drug. Interaction effects were limited to an increasing association in eating and appetite disorders using metformin and other antidiabetic drugs (i.e., drugs other than insulin, sulfonylurea, or dipeptidyl peptidase-4 inhibitors).CONCLUSION: The result of this study suggests that metformin could be beneficial for patients diagnosed with AD, other than for blood glucose control. Although, more knowledge is needed before assigning metformin a role in treating BPSD.
|
|
| 2. |
|
|
| 3. |
- Smith, Ruben, et al.
(author)
-
Correlation of in Vivo [18F]Flortaucipir with Postmortem Alzheimer Disease Tau Pathology
- 2019
-
In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 76:3, s. 310-310
-
Journal article (peer-reviewed)abstract
- Importance: In Alzheimer disease (AD), tau filaments form neuronal inclusions in neurites (neuropil threads) and in somata (neurofibrillary tangles), and neurite tau pathology constitutes the most common pathology. Positron emission tomography (PET) ligands have been developed to detect in vivo tau pathology in AD. However, the association of AD tau pathology post mortem with in vivo tau PET retention has not been established. Therefore, there is a need to investigate the associations of tau PET with postmortem tau pathology in AD. Objective: To study the association of regional in vivo retention of the tau PET ligand [18F]flortaucipir (previously known as AV1451) with the density of tau neuropathology in the corresponding brain regions in a patient with AD. Design, Setting, and Participants: The patient was a man in his 40s with AD caused by a PSEN1 mutation. Between May 2015 and December 2016, he underwent 2 [18F]flortaucipir PET scans at Lund University Hospital, Lund, Sweden. Postmortem analysis was performed 12 months after the last PET scan. Tau pathology was assessed using phosphorylated tau (AT8) immunohistochemistry and Gallyas silver staining. In addition to the regional total tau pathology burden, the density of tau-positive neurites and intrasomal tau tangles were quantified using a stereology-based method. Further, β-amyloid-containing plaques were detected using 4G8 immunohistochemistry. Data were analyzed between January 2018 and August 2018. Main Outcomes and Measures: Regional standardized uptake value ratios of [18F]flortaucipir were compared with the amount of tau pathology in the corresponding brain areas. Results: In this patient, the clinical disease symptoms progressed rapidly in life, paralleled with an annual increase of tau PET retention of 20% to 40% in many cortical regions. Compared with postmortem immunohistochemistry, regional in vivo uptake of [18F]flortaucipir was correlated with the density of tau-positive neurites (AT8: rs = 0.87; P <.001; Gallyas: rs = 0.92; P <.001), intrasomal tau tangles (AT8: rs = 0.65; P =.01; Gallyas: rs = 0.84; P <.001), and total tau burden (AT8: rs = 0.84; P <.001; Gallyas: rs = 0.82; P <.001). No correlations between [18F]flortaucipir and β-amyloid pathology were found. Conclusions and Relevance: These results indicate that [18F]flortaucipir PET retention is a robust in vivo measure of the total AD tau burden.
|
|
