Immunogenetic Epidemiology of Dementia and Parkinson’s Disease in 14 Continental European Countries: Shared Human Leukocyte Antigen (HLA) Profiles

Human leukocyte antigen (HLA), which is critically involved in immune response to foreign antigens and in autoimmunity, has been implicated in dementia and Parkinson’s disease. Here we report on the correlations between the population frequencies of 127 HLA Class I and II alleles and the population prevalence of dementia and Parkinson’s disease in 14 Continental Western European countries, extending previous work1,2. We used these correlations to construct and compare HLA profiles for each disease3. We found that (a) the HLA profiles of the two diseases were significantly correlated across both HLA Class I and Class II alleles, (b) negative (“protective”) HLA-disease correlations did not differ significantly for either HLA class, but (c) positive (“susceptibility”) HLA-disease correlations were significantly higher in dementia than in Parkinson’s disease for both HLA classes of alleles. These findings indicate that (a) dementia and Parkinson’s disease share immunogenetic HLA-related mechanisms, (b) HLA-related protective mechanisms (presumably against pathogens) do not differ between the two diseases, but (c) HLA-related susceptibility mechanisms (presumably underlying autoimmunity) are significantly stronger in dementia than in Parkinson’s disease.

White matter network damage mediates association between cerebrovascular disease and cognition

To determine whether white matter network disruption mediates the association between MRI markers of cerebrovascular disease (CeVD) and cognitive impairment. Participants (n = 253, aged ≥60 years) from the Epidemiology of Dementia in Singapore study underwent neuropsychological assessments and MRI. CeVD markers were defined as lacunes, white matter hyperintensities (WMH), microbleeds, cortical microinfarcts, cortical infarcts and intracranial stenosis (ICS). White matter microstructure damage was measured as fractional anisotropy and mean diffusivity by tract based spatial statistics from diffusion tensor imaging. Cognitive function was summarized as domain-specific Z-scores. Lacunar counts, WMH volume and ICS were associated with worse performance in executive function, attention, language, verbal and visual memory. These three CeVD markers were also associated with white matter microstructural damage in the projection, commissural, association, and limbic fibers. Path analyses showed that lacunar counts, higher WMH volume and ICS were associated with executive and verbal memory impairment via white matter disruption in commissural fibers whereas impairment in the attention, visual memory and language were mediated through projection fibers. Our study shows that the abnormalities in white matter connectivity may underlie the relationship between CeVD and cognition. Further longitudinal studies are needed to understand the cause-effect relationship between CeVD, white matter damage and cognition.

The Epidemiology of Dementia in LGBTQ Older Adults

Over 3 million or more adults aged 60 + live in the US who identify as lesbian, gay, bisexual, transgender, and/or queer (LGBTQ). Less is known about dementia risk in LGBTQ older adults. We will discuss dementia risk and related risk factors among LGBTQ adults from multiple population-based and cohort studies. We found higher rates of subjective memory problems among lesbian, bisexual and transgender adults compared to both gay men and heterosexual men and women. Using medical record data, 8% (343) of LGB adults aged 60+ were diagnosed with dementia. They were more likely to identify as male (63% vs. 44%), had a higher education level (college degree+ 63% vs. 40%) and were younger than their non-LGB counterparts. These findings highlight dementia risk and related problems among LGBTQ older adults. Future studies are needed to better understand dementia risk and recruiting, screening and improving dementia-related outcomes in LGBTQ older adults.

Prevalence and Causes of Cognitive Impairment and Dementia in a Population-Based Cohort From Northern Portugal

Background: Vascular disease may play an important role in the epidemiology of dementia in countries with high stroke incidence, such as Portugal. Objective: To assess the prevalence and etiology of cognitive impairment in a population-based cohort from Portugal. Methods: Individuals ≥55 years (n = 730) from the EPIPorto cohort were assessed using the Mini-Mental State Examination and the Montreal Cognitive Assessment. Those scoring below the age-/education-adjusted cutoff points were further evaluated to identify dementia or mild cognitive impairment (MCI) and to define its most common causes. Results: Thirty-six cases of MCI/dementia were identified, corresponding to adjusted prevalences of 4.1% for MCI and 1.3% for dementia. The most common cause of MCI/dementia was vascular (52.8%), followed by Alzheimer’s disease (36.1%). Conclusion: These findings highlight the importance of vascular cognitive impairment in the epidemiology of dementia in Portugal and carry an important public health message regarding its prevention and management, possibly extending to other countries with a high-stroke burden.