Mixed Brain Pathologies in Dementia: The BrainNet Europe Consortium Experience

Abstract

Background: Dementia results from heterogeneous diseases of the brain. Mixed disease forms are increasingly recognized. Methods: We performed a survey within brain banks of BrainNet Europe to estimate the proportion of mixed disease forms underlying dementia and age- and gender-specific influences. Results: Data collected in 9 centres from 3,303 individuals were analysed. The proportion of patients with mixed diagnoses among all cases with Alzheimer disease (AD), vascular pathology (VP), argyrophilic grain dementia (AGD), and synucleinopathies, such as Lewy body dementia (LBD), Parkinson disease (PD) and synuclein pathology only in the amygdala, was 53.3%. Mixed pathology was more frequently reported with LBD, PD, AGD, and VP than with AD. The percentage of mixed diagnoses for AGD and VP significantly differed between centres. In patients younger than 75 years, synucleinopathies, and pure forms of AD, VP, and AGD were more frequent in men. Above 75 years of age, more women had pure AD and pure AGD. Conclusions: The most obvious neuropathological alteration should not terminate the diagnostic procedure since copathology is likely to be found. Neuropathological interpretation of AGD and VP has not been sufficiently established in a consensus. Pure forms of synucleinopathies are unlikely sole substrates for dementia.

Alpha‐synuclein RT‐QuIC in the CSF of patients with alpha‐synucleinopathies

“…Many disease pathologies commonly coexist, especially AD‐related and a‐syn pathology 19. To investigate whether the presence of an alternative protein misfolding disorder can interfere with the a‐syn aggregation induced by either DLB or PD, brain homogenates from the frontal cortex of patients with mixed pathologies were examined (Fig.…”

Multiple pathologies are common and related to dementia in the oldest-old

“…Thus, this investigation adds to the growing evidence that mixed pathologies contribute to dementia in the majority of elderly and may be particularly relevant to the oldestold, who have the highest rates of mixed pathologies and dementia. 5,22 Higher-grade AD pathology was the most prevalent dementia-related pathology in this oldest-old sample (50%). Compared with younger elderly, some non-AD pathologies, including HS (17%), $3 microinfarcts (17%), amyloid angiopathy (13%), and white matter disease/SAE (8%), were found more frequently, whereas Lewy bodies (4%) and $2 macroinfarcts (4%), frontotemporal subtypes (,1%), and Parkinson disease (0%) were detected less frequently or not at all compared with younger elderly.…”

“…This study in the oldest-old extends the results of investigations performed in younger communitydwelling elderly that show dementia is generally associated with mixed rather than single brain pathologies. 7,21,22 Even in the carefully characterized patients with AD of the NIA Alzheimer Disease Centers, HS, small vessel disease, and CAA were frequent copathologies and contributed independently to cognitive loss with a magnitude similar to AD. 23 Only a handful of pathologic studies address multiple pathologies specifically in the oldest-old.…”

Challenges in the Neuropathological Diagnosis of Dementias

“…The high frequency of mixed pathologies in demented elderly was recently confirmed (Kovacs et al, 2008;. Since 50 to 85% of the brains of persons who die aged 80-90+ show appreciable CVLs (Petrovitch et al, 2005), a specific problem is the impact of CVLs in relation to AD pathology (Chui et al, 2006;Giannakopoulos et al, 2007;Jellinger, 2007a, b;Schneider et al, 2007).…”