White matter damage due to vascular, tau, and TDP-43 pathologies and its relevance to cognition

Table 3 Characteristics of autopsy cases in our dataset with TDP-43 information available

	Cohort	Age/sex	Clinical diagnosis	Hypertension (CMC^a in MCSA)	Amyloid PET (+)^b (SUVR)	Tau PET (+)^c (SUVR)	Neurodege-neration (+)^d (HVa)	TDP-43 (+)^e (FDG TDP-43 signature IMT/FSO)	Genu (ISOVF, NDI)	ITWM NDI	CGH NDI	MMSE
Case 1	MCSA	85M	Multi-domain MCI	+ (4)	− (1.28)	− (1.24)	+ (− 1.48)	+ (0.81)	0.22, 0.49	0.45	0.48	27
Case 2	MCSA	79M	Amnestic MCI	+ (2)	+ (2.12)	− (1.19)	+ (− 1.72)	+ (0.96)	0.19, 0.42	0.37	0.39	26
Case 3	MCSA	83M	Control	+ (2)	− (1.3)	− (1.16)	− (− 0.10)	+ (1.09)	0.23, 0.48	0.45	0.42	30
Case 4	MCSA	82F	Dementia	+ (2)	+ (2.92)	+ (1.73)	+ (− 1.44)	−	0.22, 0.52	0.44	0.46	24
Case 5	ADRC	81M	AD	+	+ (2.41)	+ (1.73)	+ (− 1.88)	− (0.90)	0.22, 0.46	0.45	0.42	23
Case 6	ADRC	74F	AD	−	+ (2.16)	− (1.15)	+ (− 0.91)	− (0.76)	0.11, 0.46	0.45	0.43	14
Case 7	ADRC	80M	AD	−	+ (2.98)	+ (2.08)	+ (− 3.21)	+	0.17, 0.59	0.48	0.45	20
Case 8	ADRC	75M	AD	−	+ (2.68)	+ (1.47)	+ (− 1.83)	− (0.96)	0.18, 0.51	0.47	0.45	22
Case 9	ADRC	76M	AD	+	+ (2.44)	+ (2.31)	+ (− 2.04)	+ (0.96)	0.26, 0.53	0.47	0.46	20

^aCMC—cardiovascular and metabolic conditions by ascertainment of seven conditions from REP: hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke
^bAmyloid positivity (+) = SUVR ≥ 1.48; SUVR—standard uptake value ratio
^cTau positivity (+) = SUVR ≥ 1.25
^dNeurodegeneration positivity (+) = Hippocampal volume adjusted for TIV (HVa) from MRI ≤ − 0.76
^eTDP-43 positivity (+) = presence of TDP-43 immunoreactive neuronal cytoplasmic inclusions, dystrophic neurites, or neuronal intranuclear inclusions in the amygdala in autopsy brain; TDP-43 = trans-active response DNA-binding protein of 43 kDa
ISOVF, isotropic volume fraction; CGH, parahippocampal cingulum; ITWM, inferior temporal white matter, NDI, neurite density index, IMT/FSO, inferior temporal to medial temporal (IMT) to frontal supra orbital (FSO) ratio
Mean (SD) NODDI measures among the populations investigated: For MCSA: Genu ISOVF = 0.11(0.03), Genu NDI = 0.54(0.04), CGH NDI = 0.49 (0.03), ITWM NDI = 0.49(0.04) and for ADRC: Genu ISOVF = 0.13(0.03), Genu NDI = 0.52(0.04), CGH NDI = 0.46 (0.03), ITWM NDI = 0.47(0.03))

ISSN: 2051-5960