Brain total creatine differs between primary progressive aphasia (PPA) subtypes and correlates with disease severity

Area of Science:

• Neuroimaging
• Neurology
• Biochemistry

Background:

• Primary progressive aphasia (PPA) is a neurodegenerative disorder affecting language.
• PPA presents with three distinct subtypes: logopenic (lvPPA), non-fluent (nfvPPA), and semantic (svPPA).
• Understanding subtype-specific neurochemical changes is crucial for diagnosis and treatment.

Purpose of the Study:

• To investigate differences in brain metabolite levels among PPA subtypes using magnetic resonance spectroscopy (MRS).
• To explore the association between metabolite levels and clinical symptom severity in PPA patients.
• To determine the potential of metabolites in differentiating PPA subtypes and tracking disease progression.

Main Methods:

• Magnetic resonance spectroscopy (MRS) was employed to measure tissue-corrected metabolite levels.
• Measurements were taken in the left inferior frontal gyrus (IFG) and right sensorimotor cortex (SMC) of 61 PPA patients.
• Statistical analyses were performed to compare metabolite levels across subtypes and correlate them with symptom severity.

Main Results:

• Total creatine (tCr) levels varied significantly across PPA subtypes in both the left IFG and right SMC.
• tCr levels were lowest in lvPPA and highest in svPPA, with tCr predicting diagnosis between these subtypes.
• Higher tCr in the IFG and lower glutamate/glutamine (Glx) correlated with increased disease severity.

Conclusions:

• tCr levels may serve as a biomarker for distinguishing between lvPPA and svPPA.
• Alterations in brain energy metabolism (indicated by tCr) and excitatory capacity (indicated by Glx) may underlie PPA pathology and symptoms.
• tCr and Glx show potential for understanding PPA mechanisms and monitoring disease progression.