IMO, the most important and interesting finding in the 202 and...

IMO, the most important and interesting finding in the 202 and 201 studies is that 434 reduces the progression of brain atrophy ( Claassen's index). That means fewer brain cells are dying. I think that the reason why the cells die is very similar in all brain degenerative diseases: lack of energy.

I asked ChatGPT which diseases cause brain atrophy:

Which of the diseases causing dementia demonstrates brain atrophy?

ChatGPT told:

Brain atrophy is a common feature in several diseases that cause dementia. The pattern and severity of atrophy can help distinguish between different types of dementias. Here's a breakdown:

Diseases Causing Dementia with Brain Atrophy

1. Alzheimer’s Disease (AD)

• Atrophy Pattern:

  • Early and prominent in the hippocampus, entorhinal cortex, and medial temporal lobe.

  • Later spreads to the parietal lobes, posterior cingulate, and eventually more diffuse cortical thinning.

• Clinical Relevance:

  • The hallmark MRI finding is medial temporal lobe atrophy, strongly correlated with memory impairment.

2. Frontotemporal Dementia (FTD)

• Atrophy Pattern:

  • Marked atrophy in the frontal and anterior temporal lobes.

  • Often asymmetric (one hemisphere more affected).

• Subtypes:

  • Behavioral variant (bvFTD): frontal lobe predominant.

  • Semantic variant (svPPA): anterior temporal predominant.

  • Nonfluent variant (nfvPPA): left frontal and insular regions.

3. Lewy Body Dementia (LBD)

• Atrophy Pattern:

  • Usually less severe cortical atrophy than in AD.

  • Mild parietal and occipital atrophy may be seen, sometimes with preservation of the hippocampus.

• Note: MRI findings are less specific; functional imaging (DAT scan, FDG-PET) often more informative.

4. Vascular Dementia

• Atrophy Pattern:

  • Generalized or focal atrophy related to infarcts or chronic ischemic changes.

  • White matter hyperintensities, lacunar infarcts, and subcortical ischemic changes are common.

• Subtype:

  • Subcortical ischemic vascular dementia shows prominent white matter loss with secondary cortical thinning.

5. Parkinson’s Disease Dementia (PDD)

• Atrophy Pattern:

  • Usually mild cortical atrophy compared to AD.

  • Subcortical structures (basal ganglia) may show volume loss.

  • Atrophy is less pronounced but can progress with disease duration.

6. Huntington’s Disease Dementia

• Atrophy Pattern:

  • Early and severe caudate nucleus and putamen atrophy.

  • Leads to secondary cortical thinning in advanced stages.

7. Corticobasal Degeneration (CBD) & Progressive Supranuclear Palsy (PSP)

• Atrophy Pattern:

  • CBD: Asymmetric frontoparietal cortical and basal ganglia atrophy.

  • PSP: Midbrain atrophy (“hummingbird sign”), less cortical involvement early.

✅ Summary Table

	Dementia Type	Brain Atrophy Pattern
1	Alzheimer’s	Medial temporal → parietal → diffuse cortical
2	FTD	Frontal and anterior temporal, often asymmetric
3	Lewy Body	Mild, less than AD; occipital/parietal
4	Vascular	Focal/generalized atrophy from infarcts, white matter loss
5	Parkinson’s	Mild cortical; subcortical structures affected
6	Huntington’s	Caudate and putamen → cortical thinning
7	CBD/PSP	Frontal/parietal, basal ganglia, midbrain

It is a good possibility that ATH434 will improve ATP production in mitochondria in many other diseases than MSA.