Table 1.

Histological changes assessed in five brain regions with differing severities of WMH. Scores: + mild, ++ moderate, +++ severe; (0–3) or (0–4) as stated in table, or in Supplementary Material Table 1. CAA, cerebral amyloid angiopathy; GM, grey matter; WM, white matter.

Brain region	Right frontal pole	Right anterior frontal lobe	Right temporal lobe	Right posterior frontal lobe	Right occipital lobe
WMH severity on MRI	Severe	Moderate to severe	Mild to moderate	Very mild	None
Cortical spongiosis (None/very mild/mild/moderate/severe/full thickness)	Full thickness; U fibers preserved	Full thickness; U fibers preserved	Severe	Very mild	None
Cortical neuronal loss (No loss/mild/moderate/severe)	Severe	Severe	Severe	Mild	No loss
White matter myelin pallor (0 = none; 1 = mild; 2 = moderate; 3 = severe)	3	3	3	0	0
White matter axonal loss (0 = none; 1 = mild; 2 = moderate; 3 = severe)	1	1	1	0	0
Astrogliosis (0 = none; 1 = mild; 2 = moderate; 3 = severe)	GM: 3 WM:3	GM:3 WM: 3	GM: 1 WM: 3	GM: 1 WM: 3	GM: 1 WM:1
TDP-43 (Type A) (0/+/++/+++)	++ Moderate cytoplasmic and nuclear inclusions plus threads	++/+++ Moderate cytoplasmic and nuclear inclusions plus threads	+ Sparse nuclear inclusions, a few threads	+ Sparse nuclear inclusions, a few threads	+ Only a few threads
Myelin loss (0–3)	3	3	3	0	0
Arteriolosclerosis (0–3)	1	1	1	1	1
Fibrinoid necrosis (0/1)	0	0	0	0	0
Microaneurysms (0/1)	0	0	0	0	0
Perivascular space dilation (0–3)	1	2	2	1	0
Perivascular hemosiderin leakage (0–3)	0	1	0	0	0
Microinfarcts (0/1)	0	0	0	0	0
Lacunar infarcts (0–3)	0	0	0	0	0
Large infarcts (0/1)	0	0	0	0	0
Microhemorrhage (0/1)	0	0	0	0	0
Larger hemorrhage (0/1)	0	0	0	0	0
Leptomeningeal CAA (0–4)	0	0	0	0	0
Cortical CAA (0–4)	0	0	0	0	0
Capillary CAA (0/1)	0	0	0	0	0