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Coming dissertations at MedFak

  • Alzheimer's Disease Neuropathological Change and neuronal and glial alterations in patients with idiopathic Normal Pressure Hydrocephalus Author: Sylwia Libard Link: Publication date: 2021-03-05 09:38

    Alzheimer’s disease Neuropathological Change (ADNC), i.e. amyloid β (Aβ) and hyperphosphorylated τ (HPτ), is seen in excess in the brains of subjects with AD. Idiopathic Normal Pressure Hydrocephalus (iNPH) lacks defined hallmark lesions, affects the elderly and leads to cognitive impairment, gait disturbance and urinary incontinence that can be treated with a ventriculoperitoneal shunt (VPS). A few centres around the world have obtained a brain biopsy from the area of VPS. It has been reported that the presence of ADNC in the biopsy is associated with progression to AD.

    We confirm that majority of iNPH subjects display ADNC, and the ADNC increases in extent with age, in line with AD. The HPτ pathology is sparse in majority of cases. We observed remarkable neuronal survival and loss of matrix/synapses in subjects with iNPH (paper III).

    When studying subjects with notable Aβ pathology (paper IV), we observed a stepwise increase of pyroglutamylated Aβ (pyAβ) and phosphorylated Aβ variants in iNPH. These two Aβ variants are associated with symptomatic AD and correlate with HPτ pathology. The pyAβ in the frontal cortex is a predictive marker for AD. Thus, notable Aβ pathology in presence of HPτ in iNPH is suggestive of a moderate level of ADNC.  

    When assessing changes in the extent of pathology occurring during 21 months in a frontal cortex of a subject with iNPH and AD (paper II), HPτ pathology increased in parallel with neuronal and synaptic loss, whereas Aβ pathology and astroglial activity were stable over time. In contrast, we observed reduction of microglial markers, which might explain why anti-inflammatory treatment is effective only at an early stage of AD.

    When assessing brain tissue, the section thickness must be standardised, as it affects the staining outcome and diagnosis (paper I).

    In conclusion, we have demonstrated a progressive neurodegeneration of ADNC type in a population of iNPH subjects, mimicking what is seen in subjects with AD. A brain biopsy obtained from subjects with iNPH should be obligatory. This is because when ADNC is present in the biopsy, representing prodromal AD, contact with memory clinic should be initiated.

  • Self-sampling by elderly women for the detection of HPV and cervical dysplasia Author: Ruth S. Hermansson Link: Publication date: 2021-03-01 13:04

    In Sweden, about 30% of the cervical cancer cases occur in women older than 60 and the mortality rate is as high as about 70% in this age group. There is a lack of knowledge concerning the prevalence of infection with oncogenic types of HPV, and cervical dysplasia in women of 60 years and older. Screening for oncogenic types of HPV is more effective than cytology in reducing the incidence of cervical cancer. It is established that self-collected samples are equally accurate as clinician-taken cervical samples when a validated PCR-based test is used for analysis. 

    Objectives: The overall aim was to gain knowledge about HPV infection and cervical dysplasia prevalence in elderly women and to evaluate the acceptability of repeated self-sampling at home for HPV testing.

    Material and Methods: In Paper I, we investigated the prevalence of HPV and HPV-related cervical dysplasia in 1051 elderly women aged 60 to 89 attending an outpatient gynecology clinic. A gynecologist collected these samples. In Paper II, repeated self-sampling at home for HPV testing was offered to 375 women in each of the four age groups 60, 65, 70, and 75. In Paper III, we carried out a descriptive study with quantitative and qualitative methods to describe older women’s experiences of self-sampling. In Paper IV, we investigated the incidence of oncogenic HPV and HPV-related dysplasia among 632 women aged 65 to 80 years who five years earlier had a negative HPV test.

    Results: The prevalence of HPV was just over 4% both when the samples were collected by a clinician (Paper I) and by self-sampling (Paper II). The majority of women positive in both the first and second HPV tests had dysplasia in histology. Of the women with dysplasia in histology, more than 80% had normal cytology. In Paper II, a self-collected sample was provided by 59.5% of the invited women. In Paper III, 97.2% of eligible women answered the survey, and 13 of 16 invited women participated in the interviews. Most of them reported that they prefer self-sampling because it was easy to perform, less embarrassing, and less time-consuming than a clinic visit. In Paper IV, the incidence of oncogenic HPV was 2.8% in the first test and 1.3% in the second test, and mild cervical dysplasia was found in 50% of women with persistent HPV infection.

    Conclusions: A significant proportion of elderly women were found to have a persistent HPV infection. Among them, there was a high prevalence of dysplasia as diagnosed by histology. Cytology showed extremely low sensitivity. Self-sampling at home combined with repeat HPV testing was well accepted among older women.