Differences in cognitive performance and neuroanatomy according to Alzheimer's disease pathophysiology

Ribeiro, Isadora Cristina; Gonçalves, Brenda Costa; Aventurato, Ítalo Karmann; Silva, Marjorie Cristina Rocha da; Rizzi, Liara; Rochetti, Ana Luiza Gonçalves; Fernandes, Gustavo Bruniera Peres; Cendes, Fernando; Balthazar, Marcio Luiz Figueredo

doi:10.1055/s-0046-1817040

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Original Article • Arq. Neuro-Psiquiatr. 84 (3) • 2026 • https://doi.org/10.1055/s-0046-1817040 linkcopy

Differences in cognitive performance and neuroanatomy according to Alzheimer's disease pathophysiology

Authorship SCIMAGO INSTITUTIONS RANKINGS

Background The diagnosis of predementia stages indicates an increased risk of progression to dementia. The Amyloid, Tau, and Neurodegeneration AT(N) classification considers measurements of altered proteins and the presence of neurodegeneration to classify the risk groups regarding the pathophysiology of Alzheimer's disease (AD). The cognitive and anatomical characteristics of the patients in the predementia stage according to the AT(N) classification are not fully understood.

Objective To investigate whether there are differences in the clinical and anatomical profiles among older adults in the predementia stage according to the ATN classification, and to investigate the associations involving cognition and cortical thickness and subcortical volume in the AT(N) groups.

Methods In total, 72 older adults with subjective cognitive decline and mild cognitive impairment were allocated to groups according to the AT(N) classification (AD continuum: n = 37; suspected non-AD pathophysiology: n = 8; normal biomarkers: n = 27). The participants were investigated through cognitive tests, magnetic resonance imaging scans, and cerebrospinal fluid analyses. We used multivariate and univariate analyses with post-hoc testing to verify differences among groups. In addition, linear regressions were performed to verify the interactions involving cognition and gray matter metrics.

Results The suspected non-AD pathophysiology group showed worse performance in attention/executive function than the AD continuum and normal biomarkers groups (p = 0.04). However, the ATN classification groups did not differ in terms of cortical thickness (p > 0.05). In addition, in the AD continuum group, memory was associated with left fusiform gyrus thickness (p = 0.000 uncorrected; r = 0.238).

Conclusion Cognition, but not gray matter metrics, differs among AT(N) classification groups. Memory is associated with cortical thickness in patients with positive amyloid Beta (AD continuum).

Keywords
Biomarkers; Cognition; Neuroimaging

		MCI (n = 56)		SCD (n = 16)
		Mean	SD	Mean	SD
Memory composite tests	RAVLT A1 to A5	-0.38	± 1.13	0.85	± 0.77
	RAVLT A6	-0.64	± 1.24	0.61	± 0.81
	RAVLT A7	-0.66	± 1.26	0.67	± 0.73
	RAVLT recognition	-0.33	± 1.26	0.63	± 0.55
	RCFT immediate recall	0.22	± 1.26	1.09	± 1.39
	RCFT delayed recall	0.12	± 1.26	1.05	± 1.31
Attention/executive functions composite tests	TMT part A	-0.89	± 1.53	0.37	± 1.08
Attention/executive functions composite tests	TMT part B	-0.51	± 1.51	0.8	± 0.85
Verbal fluency composite tests	SVF	-0.35	± 1.06	-0.1	± 0.70
Verbal fluency composite tests	PVF	-0.29	± 1.08	0.08	± 0.80

	AD continuum (n = 37)		SNAP (n = 8)		NB (n = 27)
	Mean	SD	Mean	SD	Mean	SD
Age (years)	64.35	± 5.63	64.25	± 6.81	65.37	± 6.69
Schooling (years)	14.13	± 4.46	12.75	± 4.43	13.37	± 3.77
Aβ (pg/mL)	689.65	± 158.71	1699.25	± 370.50	1234.19	± 185.45
pTau181 (pg/mL)	15.64	± 7.60	27.80	± 6.73	17.59	± 3.14
tTau (pg/mL)	180.85	± 72.02	321.14	± 66.00	208.27	± 27.62

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[TFN1] Abbreviations: MCI, mild cognitive impairment; PVF, phonemic verbal fluency; RAVLT, Rey Auditory Verbal Learning Test; RCFT, Rey-Osterrieth Complex Figure Test; SCD, subjective cognitive decline; SD, standard deviation; SVF, semantic verbal fluency; TMT, Trail-Making Test.