Journal of Alzheimer's Disease - Volume 69, issue 2

Authors: Skillbäck, Tobias | Kornhuber, Johannes | Blennow, Kaj | Zetterberg, Henrik | Lewczuk, Piotr | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: To alleviate the interpretation of the core Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarkers, amyloid β1–42 (Aβ42 ), total tau (T -tau), and phosphorylated tau (P -tau), the Erlangen Score (ES) interpretation algorithm has been proposed. Objective: In this study, we aim to assess the predictive properties of the ES algorithm on cognitive and neuroimaging outcomes in mild cognitive impairment (MCI). Methods: All MCI subjects with an available baseline CSF sample from ADNI-1 were included (n  = 193), and assigned an ES between 0 and 4 based on their baseline CSF biomarker profile. Structural magnetic …resonance imaging brain scans and MMSE and ADAS-Cog scores were collected at up to 7 times in follow-up examinations. Results: We observed strong and significant correlations between the ES at baseline and neuroimaging and cognitive results with patients with neurochemically probable AD (ES = 4) progressing significantly (p ≤0.01) faster than those with a neurochemically improbable AD (ES = 0 or 1), and the subjects with neurochemically possible AD (ES = 2 or 3) in-between these two groups. Conclusion: This study further demonstrates the utility of the ES algorithm as a as a tool in predicting cognitive and imaging progression in MCI patients. Show more

Keywords: Aβ1–42, Alzheimer’s disease, biomarkers, cerebrospinal fluid, Erlangen score, P-tau, T-tau

DOI: 10.3233/JAD-190067

Citation: Journal of Alzheimer's Disease, vol. 69, no. 2, pp. 551-559, 2019

Authors: Bucci, Tommaso | Menichelli, Danilo | Pignatelli, Pasquale | Triggiani, Massimo | Violi, Francesco | Pastori, Daniele

Article Type: Research Article

Abstract:  Antiphospholipid antibodies (aPL) are well-known risk factors for venous and arterial thrombosis, but their association with cognitive dysfunction has not been widely investigated in the general population and in patients with primary and secondary antiphospholipid syndrome (APS). We performed a systematic review searching MEDLINE via PubMed and Cochrane (CENTRAL) databases for observational studies reporting on the association between aPL and dementia in the general population, in subjects carrying aPL, in patients with cognitive disorder/dementia, and in primary and secondary APS. Prevalence of anticardiolipin (aCL) IgG ranged from 5.9% to 31.1% in the general population, with aCL titers being more elevated …in subjects with functional decline of cognitive functions or with neurological alterations as detected by imaging. The prevalence of aPL ranged from 6.0 to 56.6% in patients with vascular dementia. Regarding patients with primary and secondary APS, a severe cognitive deficit has been described in up to 60% of patients, 33.3% of systemic lupus erythematosus (SLE)-APS and 22.2% of SLE patients without aPL. Five studies included patients with primary APS with divergent results, while 18 studies investigated the association between aPL and cognitive impairment in patients with SLE. Of these, 14 reported a positive association between aPL, mostly aCL and LAC, and cognitive impairment while little evidence on anti β2 -Glycoprotein I exists. Mechanisms leading to cognitive dysfunction are not well characterized and may include vascular aPL-induced micro and macro-thrombosis and immune-mediated neuronal toxicity pathways in the cerebral district. Show more

Keywords: Alzheimer’s disease, antiphospholipid, antibodies, anticardiolipin, dementia, lupus anticoagulant, systemic lupus erythematous

DOI: 10.3233/JAD-181294

Citation: Journal of Alzheimer's Disease, vol. 69, no. 2, pp. 561-576, 2019

Authors: Kostev, Karel | Bohlken, Jens | Jacob, Louis

Article Type: Research Article

Abstract: Background: Previous studies focusing on the association between antidepressant use and dementia have reported controversial findings. Objective: This study aimed to compare the associations between the prescription of selective serotonin reuptake inhibitors (SSRIs) or serotonin and noradrenaline reuptake inhibitors (SNRIs) and the occurrence of dementia in patients with depression followed in Germany. Methods: This study included 20,215 patients aged 70–90 diagnosed with depression and treated in general or neuropsychiatric practices in Germany between 2010 and 2015 (index date). The main outcome of the study was the rate of dementia within 10 years after the first prescription …of SSRIs or SNRIs. For the first set of survival analyses, patients were followed until they received a dementia diagnosis or until the end of their antidepressant therapy, whereas for the second set of survival analyses, patients were followed until they received a dementia diagnosis or had their last documented visit to the practice. Results: Ten years after the index date, the rate of dementia ranged from 17.3% in escitalopram users to 36.0% in citalopram users in the first analysis, and from 30.8% in fluoxetine users to 40.4% in citalopram users in the second analysis. In the first regression model, fluoxetine (hazard ratio [HR] = 0.58), venlafaxine (HR = 0.74), and duloxetine (HR = 0.74) were associated with a decreased dementia risk compared with citalopram. In the second model, only venlafaxine significantly decreased the odds of developing dementia (HR = 0.81). Conclusion: SSRIs and SNRIs were differentially associated with the risk of dementia in patients with depression in Germany. Show more

Keywords: Dementia risk, depression, Germany, SNRIs, SSRIs

DOI: 10.3233/JAD-190239

Citation: Journal of Alzheimer's Disease, vol. 69, no. 2, pp. 577-583, 2019

Authors: Kwon, Sunkuk | Moreno-Gonzalez, Ines | Taylor-Presse, Kathleen | Edwards III, George | Gamez, Nazaret | Calderon, Olivia | Zhu, Banghe | Velasquez, Fred Christian | Soto, Claudio | Sevick-Muraca, Eva M.

Article Type: Research Article

Abstract:  Cerebrospinal fluid (CSF) outflow from the brain occurs through absorption into the arachnoid villi and, more predominantly, through meningeal and olfactory lymphatics that ultimately drain into the peripheral lymphatics. Impaired CSF outflow has been postulated as a contributing mechanism in Alzheimer’s disease (AD). Herein we conducted near-infrared fluorescence imaging of CSF outflow into the peripheral lymph nodes (LNs) and of peripheral lymphatic function in a transgenic mouse model of AD (5XFAD) and wild-type (WT) littermates. CSF outflow was assessed from change in fluorescence intensity in the submandibular LNs as a function of time following bolus, an intrathecal injection of indocyanine …green (ICG). Peripheral lymphatic function was measured by assessing lymphangion contractile function in lymphatics draining into the popliteal LN following intradermal ICG injection in the dorsal aspect of the hind paw. The results show 1) significantly impaired CSF outflow into the submandibular LNs of 5XFAD mice and 2) reduced contractile frequency in the peripheral lymphatics as compared to WT mice. Impaired CSF clearance was also evidenced by reduction of fluorescence on ventral surfaces of extracted brains of 5XFAD mice at euthanasia. These results support the hypothesis that lymphatic congestion caused by reduced peripheral lymphatic function could limit CSF outflow and may contribute to the cause and/or progression of AD. Show more

Keywords: Cerebrospinal fluid outflow, fluorescence imaging, intrathecal, lymphatic system

DOI: 10.3233/JAD-190013

Citation: Journal of Alzheimer's Disease, vol. 69, no. 2, pp. 585-593, 2019

Article Type: Correction

DOI: 10.3233/JAD-199002

Citation: Journal of Alzheimer's Disease, vol. 69, no. 2, pp. 595-596, 2019