Loss of Munc18-1 long splice variant in GABAergic terminals is associated with cognitive decline and increased risk of dementia in a community sample

Ramos-Miguel, Alfredo; Hercher, Christa; Beasley, Clare L.; Barr, Alasdair M.; Bayer, Thomas A.; Falkai, Peter; Leurgans, Sue E.; Schneider, Julie A.; Bennett, David A.; Honer, William G.

doi:10.1186/s13024-015-0061-4

Molecular Neurodegeneration

Table 2 Linear regression models^a predicting global or single-domain cognitive function

From: Loss of Munc18-1 long splice variant in GABAergic terminals is associated with cognitive decline and increased risk of dementia in a community sample

Model no. and terms	Global cognition		Episodic memory		Semantic memory		Working memory		Perceptual speed		Visuospatial ability
	(n = 302)		(n = 302)		(n = 296)		(n = 301)		(n = 293)		(n = 289)
	r ² or β^b	p-value	r ² or β	p-value	r ² or β	p-value	r ² or β	p-value	r ² or β	p-value	r ² or β	p-value
Model 1	0.328		0.394		0.208		0.174		0.189		0.121
AD pathology	−0.872	<0.001	−1.091	<0.001	−0.713	<0.001	−0.634	<0.001	−0.477	<0.001	−0.362	0.014
Macroinfarcts	−0.283	0.016	−0.253	0.039	−0.366	0.011	−0.470	0.001	−0.052	0.681	−0.065	0.657
Lewy bodies	−0.184	0.193	−0.111	0.452	−0.027	0.875	−0.102	0.533	−0.027	0.857	−0.112	0.518
Hipp sclerosis	−0.660	0.001	−1.034	<0.001	−0.662	0.005	−0.143	0.529	−0.687	0.001	−0.315	0.198
Model 2	0.345		0.406		0.226		0.193		0.193		0.123
AD pathology	−0.793	<0.001	−1.018	<0.001	−0.628	<0.001	−0.549	<0.001	−0.434	0.001	−0.323	0.032
Macroinfarcts	−0.269	0.021	−0.240	0.048	−0.347	0.014	−0.455	0.001	−0.043	0.731	−0.058	0.693
Lewy bodies	−0.141	0.314	−0.071	0.630	0.021	0.900	−0.055	0.735	−0.004	0.981	−0.088	0.611
Hipp sclerosis	−0.658	0.001	−1.032	<0.001	−0.665	0.005	−0.141	0.530	−0.686	0.001	−0.317	0.196
M18L^c	0.0010	0.003	0.0009	0.009	0.0012	0.006	0.0011	0.006	0.0005	0.141	0.0005	0.226
Model 3	0.328		0.392		0.209		0.177		0.188		0.120
AD pathology	−0.865	<0.001	−1.090	<0.001	−0.707	<0.001	−0.624	<0.001	−0.470	<0.001	−0.357	0.016
Macroinfarcts	−0.290	0.014	−0.255	0.038	−0.372	0.010	−0.483	<0.001	−0.057	0.650	−0.071	0.629
Lewy bodies	−0.175	0.217	−0.108	0.464	−0.011	0.947	−0.086	0.598	−0.018	0.907	−0.100	0.566
Hipp sclerosis	−0.670	0.001	−1.037	<0.001	−0.676	0.005	−0.160	0.480	−0.696	0.001	−0.325	0.184
M18S^c	0.0016	0.331	0.0004	0.794	0.0024	0.247	0.0027	0.150	0.0015	0.389	0.0018	0.383
Model 4	0.343		0.405		0.224		0.191		0.190		0.120
AD pathology	−0.793	0.001	−1.014	<0.001	−0.629	<0.001	−0.551	<0.001	−0.436	0.001	−0.626	0.021
Macroinfarcts	−0.267	0.022	−0.232	0.057	−0.348	0.014	−0.460	0.001	−0.047	0.714	−0.062	0.673
Lewy bodies	−0.141	0.313	−0.074	0.614	0.022	0.896	−0.053	0.745	−0.002	0.990	−0.085	0.625
Hipp sclerosis	−0.657	0.001	−1.023	<0.001	−0.667	0.005	−0.146	0.515	−0.690	0.001	−0.321	0.189
M18L^c	0.0010	0.006	0.0011	0.006	0.0011	0.013	0.0010	0.017	0.0005	0.217	0.0004	0.343
M18S^c	−0.0003	0.877	−0.0015	0.419	0.0003	0.890	0.0009	0.669	0.0006	0.741	0.0010	0.658

Abbreviations: AD Alzheimer’s disease Hipp, hippocampal; M18L/S, Munc18-1 long/short splice variant
^aAll models included terms (not shown) for age, sex, education, microinfarcts, arteriolosclerosis, and atherosclerosis
^bValues are whole model adjusted r-squared, or individual β-coefficients for each term
^cStandardized M18L/S values (z-scores) were used

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