Substantia nigra MRI markers are lower in Alzheimer's disease and are linked to general cognitive function
Friedrich Krohn, Mousumi Sarkar, Hartmut Schütze, Panagiotis Iliopoulos, Lucía Penalba-Sánchez, Dorothea Hämmerer, Renat Yakupov, Falk Lüsebrink, Annika Spottke, Anja Schneider, Nina Roy, Enise Incesoy, Michael Heneka, Ingo Kilimann, Luca Kleineidam, Stefan J Teipel, Frederic Brosseron, Doreen Goerss, Wenzel Glanz, Matthias Schmid, Ayda Rostamzadeh, Michael Wagner, Klaus Fliessbach, Frank Olaf Jessen, Emrah Düzel, Matthew J BettsAbstract
Individuals with Alzheimer’s disease dementia show Alzheimer's disease pathology and a heterogeneous degeneration of the Substantia Nigra (SN) postmortem. However, it is unclear how SN degeneration is related to cognitive dysfunction across the Alzheimer’s disease dementia continuum. In this study, using data from the prospective DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE), we investigated whether in vivo SN MRI measures are lower in individuals with clinically defined Alzheimer’s disease dementia than in healthy control subjects (HC) and if they are associated with hippocampal functional activity during the processing of novel visual stimuli and subsequent recognition memory.
160 DELCODE participants (69 years ±6 years, 88 men), including 79 HC, 70 individuals with subjective cognitive decline (SCD), 17 individuals with mild cognitive impairment (MCI), and 10 individuals with Alzheimer’s disease dementia, completed a scene novelty and encoding task and a 3T SN-sensitive MRI scan, from which the two in-vivo SN measures MRI contrast and volume were calculated and harmonized between scanner sites while preserving diagnostic group differences. For 71 individuals, CSF levels of phosphoTau, total tau, and amyloid-beta 42/40 ratio (Aß42/40) were available. All individuals completed a neuropsychological task battery from which a global cognitive score was calculated. In separate models, we assessed the relationship between SN MRI markers and CSF levels of Alzheimer’s disease, the global cognitive score, hippocampal novelty activation, and recognition memory while accounting for age, sex, years of education, and total intracranial volume (TIV).
SN volume but not SN MRI contrast was lower in individuals with clinical Alzheimer’s disease dementia (One-way analyses of covariance (ANCOVA); F(156,4)= 5.6665, p=0.0010, n=160). SN MRI contrast and volume were not associated with Aß42/40, ptau, and total tau CSF levels (all p>0.1) or hippocampal novelty activation (all p>0.1). Moreover, SN volume was positively associated with recognition memory (R^2 = 0.07, p<0.001, n= 159), global cognition (R^2 = 0.38, p<0.0001, n= 160), and years of education (R^2 = 0.03, p=0.036, n= 160),
Our study emphasizes the potential of using in vivo SN MRI markers to study the impact of SN degeneration on general cognitive impairment and recognition memory in an Alzheimer’s disease dementia cohort. Our results motivate future longitudinal studies to explore how SN volume and SN contrast change with disease progression, how these are differentially associated with cognitive decline, and how SN volume and SN contrast might be related to other dopamine-dependent cognitive functions and dysfunctions.