Efficacy and Safety of Memantine Hydrochloride, a low affinity antagonist to N-Methyl-D-Aspartate (NMDA) type receptors, in the prevention of cognitive decline and disease progression in older people with Down's syndrome, with and without dementia

Abstract Background Neuroinflammation may contribute to psychiatric symptoms in older people, in particular in the context of Alzheimer’s disease (AD). We sought to identify systemic and central nervous system (CNS) inflammatory alterations associated with neuropsychiatric symptoms (NPS); and to investigate their relationships with AD pathology and clinical disease progression. Methods We quantified a panel of 38 neuroinflammation and vascular injury markers in paired serum and cerebrospinal fluid (CSF) in a cohort of cognitively normal and impaired older subjects. We performed neuropsychiatric and cognitive evaluations and measured CSF biomarkers of AD pathology. Multivariate analysis determined serum and CSF neuroinflammatory alterations associated with NPS, considering cognitive status, AD pathology, and cognitive decline at follow-up visits. Results NPS were associated with distinct inflammatory profiles in serum, involving eotaxin-3, interleukin (IL)-6 and C-reactive protein (CRP); and in CSF, including soluble intracellular cell adhesion molecule-1 (sICAM-1), IL-8, 10 kDa interferon-γ-induced protein, and CRP. AD pathology interacted with CSF sICAM-1 in association with NPS. Presenting NPS was associated with subsequent cognitive decline which was mediated by CSF sICAM-1. Conclusions Distinct systemic and CNS inflammatory processes are involved in the pathophysiology of NPS in older people. Neuroinflammation may explain the link between NPS and more rapid clinical disease progression.

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Adaptación y validación del Cambridge Examination for Mental Disorders of Older People with Down’s Syndrome and Others with Intellectual Disabilities (CAMDEX-DS) en población española con discapacidad intelectual

Revista de Neurología ◽

10.33588/rn.5708.2013259 ◽

2013 ◽

Vol 57 (08) ◽

pp. 337 ◽

Cited By ~ 5

Author(s):

Susanna Esteba Castillo ◽

Albert Dalmau Bueno ◽

Núria Ribas Vidal ◽

Marta Vilà Alsina ◽

Ramon Novell Alsina ◽

...

Keyword(s):

Mental Disorders ◽

Older People ◽

Intellectual Disabilities ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Discapacidad Intelectual

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The clinical presentation, diagnosis, treatment and long term outcome of germ cell tumor in 85 patients with Down syndrome.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.554 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 554-554

Author(s):

Emma Weatherford ◽

Jue Wang

Keyword(s):

Germ Cell ◽

Disease Progression ◽

Germ Cell Tumor ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Cell Tumor ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Long Term Outcome

554 Background: The main objective of this study was to determine the clinical features, treatment, clinical outcome and prognosis of Down's syndrome (DS) patients with germ cell tumor (GCT). Methods: Literature search based on PubMed search was performed using the following keywords: “Germ cell tumor (GCT)” and “Down's syndrome”. A total of 85 cases of GCT in DS patients published in literature between January 1985 and October 2017 were identified. Results: Our final cohort of GCT in DS include 44 cases of testicular germ cell tumor (TGCT); 22 intracranial GCT, 2 primary mediastinal GCT, 3 gastrointestinal GCT, 9 retroperitoneal GCT, and 5 cases of ovarian GCT. The median age of forty-four testicular GCT was 30 years (range 2 years – 50 years). In most cases, cancer was diagnosed following the discovering of swelling by care provider or found incidentally (either painless or painful) in the region of the testes, although abdominal pain was a symptom in a few cases. 29 (66%) patients were diagnosed with seminoma and 15 (34%) with non-seminoma. In the seminoma group, 18 (62%) patients were diagnosed with stage I , 9 (31%) with stage II and 2 (7%) with stage III. In the non-seminoma group, 4 (27%) patients were diagnosed with stage I, 5 (33%) with stage II and 6 (40%) with stage III. Nearly all patients (94%) underwent orchiectomy. 52% patients received chemotherapy, with BEP being the most common administered regimen. 7 patients had retroperitoneal lymph node dissection ( RPLND). In the seminoma group, there were 5 deaths, 3 related to disease progression, 2 related to comorbidities, 1 died during chemotherapy. In the non-seminoma group, there were 2 deaths, 1 related to disease progression, 1 died during chemotherapy. The overall survival at 5 years for stage I was 100%, 76% for stage II and 68% for stage III. Conclusions: In this largest cohort of GCT in DS, we found TGCTs are often diagnosed at stage II or III. In addition, delayed diagnosis, comorbidities likely contributed to the inferior outcome in stage II/III TGCTs in patients with DS. Emphasis on education, better communication, early screening and detection, are needed to improve the outcome in this population.

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