1. Comorbid neuropathology and atypical presentation of Alzheimer's disease
- Author
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Pina‐Escudero, Stefanie D, La Joie, Renaud, Spina, Salvatore, Hwang, Ji‐Hye, Miller, Zachary A, Huang, Eric J, Grant, Harli, Mundada, Nidhi S, Boxer, Adam L, Gorno‐Tempini, Maria Luisa, Rosen, Howard J, Kramer, Joel H, Miller, Bruce L, Seeley, William W, Rabinovici, Gil D, and Grinberg, Lea Tenenholz
- Subjects
Biological Psychology ,Psychology ,Acquired Cognitive Impairment ,Neurodegenerative ,Neurosciences ,Brain Disorders ,Alzheimer's Disease ,Dementia ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Aging ,2.1 Biological and endogenous factors ,4.1 Discovery and preclinical testing of markers and technologies ,Neurological ,atypical Alzheimer's disease ,clinicopathological correlation ,comorbidities ,neuropathology ,post mortem ,selective vulnerability ,Genetics ,Biological psychology - Abstract
IntroductionAlzheimer's disease (AD) neuropathological changes present with amnestic and nonamnestic (atypical) syndromes. The contribution of comorbid neuropathology as a substratum of atypical expression of AD remains under investigated.MethodsWe examined whether atypical AD exhibited increased comorbid neuropathology compared to typical AD and if such neuropathologies contributed to the accelerated clinical decline in atypical AD.ResultsWe examined 60 atypical and 101 typical AD clinicopathological cases. The number of comorbid pathologies was similar between the groups (p = 0.09). Argyrophilic grain disease was associated with atypical presentation (p = 0.008) after accounting for sex, age of onset, and disease duration. Vascular brain injury was more common in typical AD (p = 0.022). Atypical cases had a steeper Mini-Mental Status Examination (MMSE) decline over time (p = 0.033).DiscussionComorbid neuropathological changes are unlikely to contribute to atypical AD presentation and the steeper cognitive decline seen in this cohort.HighlightsAutopsy cohort of 60 atypical and 101 typical AD; does comorbid pathology explain atypical presentation?Atypical versus Typical AD: No significant differences in comorbid neuropathologies were found (p = 0.09).Argyrophilic Grain Disease Association: significantly correlates with atypical AD presentations, suggesting a unique neuropathological pattern (p = 0.008).Vascular Brain Injury Prevalence: Vascular brain injury is more common in typical AD than in atypical AD (p = 0.022).Cognitive Decline in Atypical AD: Atypical AD patients experience a steeper cognitive decline measured by MMSE than those with typical AD despite lacking more comorbid neuropathology, highlighting the severity of atypical AD pathogenesis (p = 0.033).
- Published
- 2024