Alzheimer's disease and mixed pathologies as a hidden contributor to fatal hypothermia: A large-scale forensic autopsy-based study.

There is a paucity of autopsy-based studies providing detailed neuropathological characteristics of fatal hypothermia cases, particularly in trauma-associated cases. Hence, this study investigated 2054 serial autopsy cases in which histopathological examination of all organs, including the brain, could be performed. We identified 168 cases (75 female and 93 male patients) of fatal hypothermia and examined the clinical and neuropathological characteristics in these cases. Patients aged ≥65 years constituted 80% of the cohort (135 cases). Cognitive impairment (CI) was identified in 39% of cases with available clinical histories, and approximately half of these cases were presumed to have developed hypothermia while wandering, based on clinical history and the circumstances of discovery. Alzheimer's disease was the most commonly identified pathology, affecting 40% of the total and approximately two-thirds of patients aged ≥80 years. CI caused by multiple pathologies, especially two, was more frequently observed than by a single pathology. The most common manner of exposure to cold temperatures was accidents (120 cases), including 35 cases with multiple traumatic injuries, most likely resulting from falls. In these cases, the trauma was considered the primary cause of immobility, leading to subsequent exposure to cold environments. Importantly, 30 (86%) of these trauma-associated cases showed one or more neuropathological conditions, and CI was documented in 13, with four presumed to have fallen while wandering. Notable neuropathological manifestations were also observed in eight of the 33 cases of patients aged less than 65 years. Our results demonstrate that neurodegenerative diseases, especially Alzheimer's disease, are underlying conditions in fatal hypothermia in the elderly and in relatively younger individuals, suggesting that they may contribute to its onset. These findings highlight the necessity for comprehensive neuropathological examination in all forensic autopsy cases of hypothermia.