Pure argyrophilic grain disease revisited: independent effects on limbic, neocortical, and striato-pallido-nigral degeneration and the development of dementia in a series with a low to moderate Braak stage

Yokota, Osamu; Miki, Tomoko; Nakashima-Yasuda, Hanae; Ishizu, Hideki; Haraguchi, Takashi; Ikeda, Chikako; Hasegawa, Masato; Miyashita, Akinori; Ikeuchi, Takeshi; Nishikawa, Naoto; Takenoshita, Shintaro; Sudo, Koichiro; Terada, Seishi; Takaki, Manabu

doi:10.1186/s40478-024-01828-6

Table 3 Multivariate analyses of predictors for neuronal loss in limbic, neocortical, and subcortical regions

From: Pure argyrophilic grain disease revisited: independent effects on limbic, neocortical, and striato-pallido-nigral degeneration and the development of dementia in a series with a low to moderate Braak stage

	Odds ratio	95% CI	p value
Multivariate ordered logistic regression analyses
Amygdala (n = 63)^a
Age at death	1.07	1.01–1.14	0.0179*
Braak NFT stage	0.67	0.35–1.29	0.2320
Saito AG stage	3.18	1.73–5.84	< 0.001**
LATE-NC stage	0.62	0.27–1.44	0.2659
Entorhinal cortex (n = 63)^a
Age at death	1.01	0.98–1.05	0.3961
Braak NFT stage	0.82	0.42–1.60	0.5656
Saito AG stage	2.38	1.29–4.39	0.0056**
LATE-NC stage	1.94	0.89–4.22	0.0948
CA1 in the hippocampus^a
Age at death	0.76	0.55–1.05	0.0920
Braak NFT stage	5.37	0.50–57.69	0.1656
Saito AG stage	220.70	1.50–32565.95	0.0342*
LATE-NC stage^b	138.28	0.74–25,781.42	0.0646
Lateral occipitotemporal gyrus (n = 63)^a
Age at death	1.00	0.96–1.03	0.8281
Braak NFT stage	0.42	0.17–1.04	0.0619
Saito AG stage	2.82	1.39–5.71	0.0040**
LATE-NC stage	3.93	1.43–10.85	0.0082**
Inferior temporal gyrus (n = 63)^c
Age at death	1.01	0.92–1.12	0.8326
Braak NFT stage	0.41	0.14–1.17	0.0951
Saito AG stage	2.88	1.36–6.11	0.0059**
LATE-NC stage	2.97	1.01–8.77	0.0485*
Middle temporal gyrus (n = 63)^a
Age at death	1.00	0.91–1.11	0.9727
Braak NFT stage	0.52	0.20–1.37	0.1854
Saito AG stage	2.92	1.34–6.33	0.0068**
LATE-NC stage	3.74	1.24–11.24	0.0190*
Superior temporal gyrus (n = 60)^a
Age at death	1.03	0.92–1.16	0.6320
Braak NFT stage	0.56	0.20–1.56	0.2656
Saito AG stage	6.74	2.16–21.02	0.0010**
LATE-NC stage	0.83	0.25–2.73	0.7634
Insular cortex (n = 62)^a
Age at death	0.99	0.95–1.04	0.8149
Braak NFT stage	0.73	0.32–1.68	0.4615
Saito AG stage	4.28	1.86–9.84	< 0.001**
LATE-NC stage	2.15	0.82–5.59	0.1179
Cingulate gyrus (n = 60)^a
Age at death	1.01	0.92–1.12	0.7919
Braak NFT stage	0.70	0.30–1.63	0.4052
Saito AG stage	2.75	1.27–5.95	0.0100**
LATE-NC stage	1.94	0.72–5.21	0.1891
Middle frontal gyrus (n = 63)^a
Age at death	0.96	0.87–1.07	0.4509
Braak NFT stage	0.52	0.20–1.38	0.1903
Saito AG stage	5.44	2.11–14.01	< 0.001**
LATE-NC stage	1.37	0.47–3.96	0.5626
Orbital gyrus (n = 53)^a
Age at death	0.97	0.87–1.07	0.5166
Braak NFT stage	0.45	0.17–1.23	0.1208
Saito AG stage	5.84	2.21–15.43	< 0.001**
LATE-NC stage	1.80	0.55–5.95	0.3326
Substantia nigra (n = 63)^a
Age at death	0.94	0.84–1.04	0.1985
Braak NFT stage	0.73	0.28–1.88	0.5114
Saito AG stage	2.76	1.25–6.09	0.0116*
LATE-NC stage	1.94	0.67–5.60	0.2230
Binomial logistic regression analysis
Caudate nucleus (n = 63)^d
Age at death	0.87	0.75–1.02	0.0821
Moderate NFTs^e	1.71	0.07–39.80	0.7393
Severe AGs^f	20.02	1.29–310.27	0.0321*
Moderate LATE-NC^g	53.87	1.28–2262.10	0.0366*
Putamen (n = 63)^d
Age at death	0.84	0.67–1.05	0.1206
Moderate NFTs^e	0.10	0.00–17.44	0.3783
Severe AGs^f	473.03	2.55–87,745.07	0.0208*
Moderate LATE-NC^g	68.84	0.22–21,175.06	0.1477
Globus pallidus (n = 63)^d
Age at death	0.98	0.83–1.16	0.8167
Moderate NFTs^e	0.11	0.00–6.49	0.2895
Severe AGs^f	85.90	3.24–2277.13	0.0077**
Moderate LATE-NC^g	6.82	0.15–317.26	0.3270

30 pAGD cases and 34 control cases were examined.
CI confidence interval, NFT neurofibrillary tangle, AG argyrophilic grains, LATE-NC limbic-predominant age-related TDP-43 encephalopathy neuropathologic change.
^aThe dependent variable was a four-point staging system of neuronal loss (none, mild, moderate, and severe. The definitions are noted in the text) in each region. The age at death, Braak NFT stage, Saito AG stage, and LATE-NC stage were submitted as independent variables.
^bLATE-NC stages 1–3 were combined.
^cNeuronal loss stages 2 and 3 were combined.
^dThe dependent variable was the presence or absence of neuronal loss (stages 0 or 1–3) in each region.
^eBraak NFT stages III–IV.
^fBecause all diffuse form pAGD cases fit the criteria of Saito AG stage III, diffuse form was regarded as Saito AG stage III in statistical analyses.
^gLATE-NC stages 2. No pAGD or control case had LATE-NC in stage 3.
*: p < 0.05, **: p < 0.01

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