Poster exhibited at GPSC Student Showcase, November 7th, 2014, University of Arizona. / Given the early emergence of Alzheimer’s disease (AD) related pathology in Down syndrome (DS; Trisomy 21), it is possible that changes may be evident in childhood or adolescence in Apolipoprotein (APOE) e3/e4 or e4/e4 genotypes in relation to e3/e3 genotypes. Given findings of early involvement of striatum amyloid beta (Aβ) peptide deposition in DS, we propose that a profile of executive and inhibitory control dysfunction will be found in youth carrying the risk e4 allele. From a pool of 72 children and adolescents with DS we examined a sub-sample with the risk e4 allele (n = 8; e3/e4) and without the risk e4 allele (n = 8; e3/e3). Participants were matched for age and ethnicity (range 8 - 21 years; mean age 14 years). Karyotypes were gathered from medical records, confirming a diagnosis of Trisomy 21. We collected genetic information (Oragene saliva kit) in home; they were sent to the Emory Biomarker Service Center to determine genotypes. We administered the Kaufman Brief Intelligence Test (KBIT-2) and a set of cognitive outcomes measures validated for Down syndrome, the Arizona Cognitive Test Battery. Results from the KBIT-2 indicated no significant differences in verbal raw score (p = 0.65), non-verbal raw score (p = 0.69), or intelligence quotient (IQ) (p = 0.32). Neuropsychological test scores did differ; with poorer performance in the e4 sample on the CANTAB Paired Associates Learning task (p = 0.05) and parent/caregiver reports of working memory (p = 0.08). Therefore, as early as adolescence some changes may be seen in e4 carriers.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Introduction: Cognitive impairment is converted for 15% to Alzheimer’s disease (AD), which is incurable. The aim of this study is to investigate whether Herpes simplex virus type 1 (HSV1) and its interaction with allele ε4 of Apolipoprotein E (ApoE-ε4) may be possible risk factors for cognitive impairment. Here, suggestions for implementation of Precision Public Health (PPH) is also presented; population studies of relevant biomarkers of infectious burden and data from health outcomes with the aim of remedying public health crises, monitoring diseases, anticipating risks and using public health initiatives adapted to risk groups to increase understanding of diseases, such as AD. Method: An analysis of 1013 people aged 75 from the cohort, Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), was performed. Linear mixed models (LMM) were used to investigate whether anti-HSV1 IgG and ApoE-ε4 are associated with risk of developing cognitive impairment over 5 years. Anti-HSV1 IgG in serum was detected by Enzyme-linked immunosorbent assays and cognitive impairment was examined by Mini Mental State Examination. Results: Neither anti-HSV1 IgG positivity nor its interaction with ApoE-ε4 were associated with cognitive impairment. Discussion: Studies of HSV1 without HSV2 or HSV show mixed results. Therefore, we do not yet have sufficient evidence to implement PPH-interventions against these risks. Other cognitive tests that are more sensitive to early changes and adjustment for underrepresented groups may potentially contribute to a more accurate analysis. / Bakgrund: Kognitiv nedsättning övergår för 15 % till Alzheimers sjukdom (AD) som är obotlig. Denna studie har målsättningen att undersöka om Herpes simplex virus typ 1 (HSV1) och dess interaktion med riskvarianten allel ε4 av genen Apolipoprotein E (ApoE-ε4) kan vara möjliga riskfaktorer för kognitiv nedsättning. I arbetet diskuteras även hur man genom Precision Public Health (PPH) kan studera befolkningen med avseende på relevanta biomarkörer och data från hälsoutfall med syfte att avhjälpa folkhälsokriser, övervaka sjukdomar och förutse risker såsom sjunkande kognition och med folkhälsoinsatser anpassade till riskgrupper öka förståelsen av dessa tillstånd. Metod: En analys av 1013 personer 75 år ur kohorten ”Prospecive Investigation of the Vasculature in Uppsala Seniors” (PIVUS). Linear mixed models (LMM) användes för att undersöka om anti-HSV1 IgG och ApoE-ε4 är associerade med kognitiv nedsättning under 5 år. Anti-HSV1 IgG i serum detekterades med ”Enzyme-linked immunosorbent assays” och kognitiv nedsättning undersöktes med Mini Mental State Examination. Resultat: Anti-HSV1 IgG positivitet var inte associerat med kognitiv nedsättning. Anti-HSV1 IgG positivitet och samtidig ApoE-ε4 var inte heller associerat med kognitiv nedsättning. Diskussion: Andra studier av endast HSV1 utan HSV2 eller HSV visar blandade resultat, varför kunskapsläget idag inte stödjer tillämpning av PPH-interventioner mot dessa risker. Andra kognitiva mått som är känsligare för små förändringar nära intakt kognition samt justering för underrepresenterade grupper kan möjligen bidra till säkrare analys.

Introduction: Alzheimer's disease is a neurodegenerative disease that initially manifests itself primarily as impaired short-term memory and impaired language ability. The course of the disease is mainly due to an atrophy in the brain that can be attributed to the protein amyloid B and tau. Monoclonal antibodies that target Alzheimer's disease often have a high rate of cerebral edema, where proteinaceous fluid leaks into the extracellular space of the brain and creates edema. Some of the most common symptoms for amyloid-related imaging abnormalities (ARIA-E) are headache, dizziness, and blurred vision. In a few cases, patients with ARIA-E need to be hospitalized for observation, but most show a decline in ARIA-E within one to two months. Objective: To investigate the frequency of ARIA-E in clinical studies of monoclonal antibodies to patients with Alzhiemer's disease and to investigate the role of the ApoE4 allele in the development of ARIA-E. Method: Literature review of five RCT studies based on four different monoclonal antibodies. PubMed was used to search for the RCT-studies. Results: ARIA-E varies between different types of antibodies. ARIA-E usually occurs early in treatment when the degree of amyloid b is highest in the brain. Most cases are asymptomatic and treatment resumes within 1-2 months. Conclusion: Aria-E frequency correlates strongly with dose strength as well as APOE4 -status and most of the incidences are asymptomatic. With the right titration and individually selected drugs as well as individual dosages a safe care can be established for patients with Alzheimer's disease. If treatment is initiated at an early stage, the risk of side effects is reduced and more neurons can be saved from atrophy. The combination of several different types of medicine will further reduce the risk of ARIA-E.