A population‐based investigation of brain changes related to Alzheimer’s disease in middle‐aged adults in Brazil

Background Given the progressive nature of neurodegenerative pathologies, great effort has been made to create diagnostic tools for detecting neurodegenerative changes in their early stages. However, the lack of information about the frequency of neurodegenerative changes in mid‐age adults impacts biomarker interpretation and sensitivity improvement. In addition, recent clinicopathological studies have shown than even a low Alzheimer’s disease (AD) neuropathological burden can significantly impact neuropsychiatric function. Finally, clinicopathological studies point to a role of small cerebrovascular changes in the cognitive decline of individuals with zero or low neurodegenerative burden; however, it remains unclear if small vascular brain lesions can impact cognition in younger mid‐age individuals. Method We evaluated the presence of AD neuropathological changes and their relationship with cognitive impairment, neuropsychiatric symptoms and risk factors in a multiethnic and heterogeneous group under 65 years of age at the moment of death, most of them with low educational level (Table 1). A semi‐structured interview with an informant was performed to obtain socioeconomic and clinical data. Internationally accepted neuropathological criteria were used for pathologic diagnosis. Result Some degree of neurofibrillary pathology was found in 53% (n = 145) of the individuals, while neuritic plaques were found in 10% (n = 26) of the cases, regardless of the presence of cognitive impairment or neuropsychiatric symptoms. AD‐type pathology burden was similar among individuals with and without cognitive impairment. However, a higher frequency of vascular pathology (p