Validation of longitudinal change in proper name recall with pTau217 as a marker of early cognitive decline in cognitively unimpaired adults at risk for Alzheimer's disease dementia
Restricted accessResearch articleFirst published online 2026
Validation of longitudinal change in proper name recall with pTau217 as a marker of early cognitive decline in cognitively unimpaired adults at risk for Alzheimer's disease dementia
Previous work has shown that proper name recall from the Logical Memory (LM) task is sensitive to PET and cerebrospinal fluid biomarkers of Alzheimer's disease (AD) in older adult populations. These findings indicate potential utility in identifying preclinical AD.
Objective
The purpose of this study is to validate previous findings of the association of proper name recall and blood-based plasma pTau217.
Methods
Participants came from the Wisconsin Registry for Alzheimer's Prevention study. We fit linear mixed effects models of longitudinal LM and proper name recall as a function of most recent pTau217 values. Follow-up analyses added interaction terms to models for group differences in sex and APOE ε4 allele carriage. As an exploratory aim, logistic regression models were used to examine if proper name recall aided in predicting clinical diagnosis.
Results
Participants with higher concentrations of pTau217 showed a steeper decline on both conventional LM and proper name recall. APOE ε4 allele carriers with higher concentrations of pTau217 showed a greater decline in longitudinal task performance, while there was no significant interaction for sex, indicating that men and women with high pTau217 show similar rates of decline.
Conclusions
Our findings validate that proper name recall is sensitive to blood-based pTau217. Measuring proper name recall may be an efficient marker assessing early cognitive change that could be leveraged when designing future cognitive tests.
BraakHBraakE. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol1991; 82: 239–259.
2.
JackCRJr.BennettDABlennowK, et al.NIA-AA Research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement2018; 14: 535–562.
3.
SperlingRAAisenPSBeckettLA, et al.Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement2011; 7: 280–292.
4.
BetthauserTJBilgelMKoscikRL, et al.Multi-method investigation of factors influencing amyloid onset and impairment in three cohorts. Brain2022; 145: 4065–4079.
5.
KoscikRLBetthauserTJJonaitisEM, et al.Amyloid duration is associated with preclinical cognitive decline and tau PET. Alzheimers Dement (Amst)2020; 12: e12007.
6.
BelderCRSBocheDNicollJAR, et al.Brain volume change following anti-amyloid β immunotherapy for Alzheimer's disease: amyloid-removal-related pseudo-atrophy. Lancet Neurol2024; 23: 1025–1034.
7.
SöderbergLJohannessonMNygrenP, et al.Lecanemab, aducanumab, and gantenerumab - binding profiles to different forms of amyloid-beta might explain efficacy and side effects in clinical trials for Alzheimer's disease. Neurotherapeutics2023; 20: 195–206.
8.
HaleMRLanghoughRDuL, et al.Associations between recall of proper names in story recall and CSF amyloid and tau in adults without cognitive impairment. Neurobiol Aging2024; 133: 87–98.
9.
MuellerKDKoscikRLDuL, et al.Proper names from story recall are associated with beta-amyloid in cognitively unimpaired adults at risk for Alzheimer's disease. Cortex2020; 131: 137–150.
10.
BraakHBraakE. Evolution of the neuropathology of Alzheimer's disease. Acta Neurol Scand1996; 94: 3–12.
11.
AminoffEMKveragaKBarM. The role of the parahippocampal cortex in cognition. Trends Cogn Sci2013; 17: 379–390.
12.
DamasioHGrabowskiTJTranelD, et al.A neural basis for lexical retrieval. Nature1996; 380: 499–505.
13.
PapagnoCCapitaniE. Proper name anomia: a case with sparing of the first-letter knowledge. Neuropsychologia1998; 36: 669–679.
14.
PisoniASperandeoPRLauroR, et al.The role of the left and right anterior temporal Poles in people naming and recognition. Neuroscience2020; 440: 175–185.
15.
PowelJ. Wechsler memory scale-revised: david A. Wechsler. New York: the Psychological Corporation. Harcourt Brace Jovanovich, Inc, 1987. 150 pp. Arch Clin Neuropsychol1988; 3: 397–403.
16.
JanelidzeSBaliDAshtonNJ, et al.Head-to-head comparison of 10 plasma phospho-tau assays in prodromal Alzheimer's disease. Brain2023; 146: 1592–1601.
17.
AshtonNJJanelidzeSMattsson-CarlgrenN, et al.Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer's trial selection and disease monitoring. Nat Med2022; 28: 2555–2562.
18.
PalmqvistSJanelidzeSQuirozYT, et al.Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders. JAMA2020; 324: 772–781.
19.
AshtonNJBrumWSDi MolfettaG, et al. Diagnostic accuracy of a plasma phosphorylated tau 217 immunoassay for Alzheimer disease pathology. JAMA Neurol2024; 81: 255–263.
20.
BrickmanAMManlyJJHonigLS, et al.Plasma p-tau181, p-tau217, and other blood-based Alzheimer's disease biomarkers in a multi-ethnic, community study. Alzheimers Dement2021; 17: 1353–1364.
21.
CowmanDLanghoughROlsonH, et al.Sex differences in story recall decline in preclinical Alzheimer's disease. Brain Commun2025; 7: fcaf169.
22.
FarrerLACupplesLAHainesJL, et al.Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA1997; 278: 1349–1356.
23.
CorderEHSaundersAMStrittmatterWJ, et al.Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science1993; 261: 921–923.
24.
KimJBasakJMHoltzmanDM. The role of apolipoprotein E in Alzheimer's disease. Neuron2009; 63: 287–303.
25.
KapurSSharadSKapoorM, et al.Apoe genotypes: risk factor for Alzheimer’s disease. J Indian Acad Clin Med2006; 7: 118–122.
26.
BelloyMEAndrewsSJLe GuenY, et al.APOE Genotype and Alzheimer disease risk across age, sex, and population ancestry. JAMA Neurol2023; 80: 1284–1294.
27.
SunJZhuZChenK, et al.APOE Ε4 allele accelerates age-related multi-cognitive decline and white matter damage in non-demented elderly. Aging (Albany NY)2020; 12: 12019–12031.
28.
WilliamsOAAnYArmstrongNM, et al.Apolipoprotein E ε4 allele effects on longitudinal cognitive trajectories are sex and age dependent. Alzheimers Dement2019; 15: 1558–1567.
29.
IhleABunceDKliegelM. APOE Ε4 and cognitive function in early life: a meta-analysis. Neuropsychology2012; 26: 267–277.
30.
MarioniRECampbellAScotlandG, et al.Differential effects of the APOE e4 allele on different domains of cognitive ability across the life-course. Eur J Hum Genet2016; 24: 919–923.
31.
JohnsonSCKoscikRLJonaitisEM, et al.The Wisconsin Registry for Alzheimer's Prevention: a review of findings and current directions. Alzheimers Dement (Amst)2018; 10: 130–142.
32.
WechslerD. Wechsler memory scale-revised. San Antonio, TX: Psychological Corporation, 1987.
33.
DowlingNMHermannBLa RueA, et al.Latent structure and factorial invariance of a neuropsychological test battery for the study of preclinical Alzheimer's disease. Neuropsychology2010; 24: 742.
34.
KoscikRLLa RueAJonaitisEM, et al.Emergence of mild cognitive impairment in late middle-aged adults in the Wisconsin registry for Alzheimer's prevention. Dement Geriatr Cogn Disord2014; 38: 16–30.
35.
ClarkLRRacineAMKoscikRL, et al.Beta-amyloid and cognitive decline in late middle age: findings from the Wisconsin Registry for Alzheimer's Prevention study. Alzheimers Dement2016; 12: 805–814.
36.
Langhough KoscikRHermannBPAllisonS, et al.Validity evidence for the research category, “cognitively unimpaired - declining,” as a risk marker for mild cognitive impairment and Alzheimer's disease. Front Aging Neurosci2021; 13: 688478.
37.
R Development Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing, 2025.
38.
BatesD. Fitting linear mixed-effects models using lme4. arXiv preprint arXiv:14065823 2014.
39.
BurnhamKPAndersonDR. Multimodel inference:understanding AIC and BIC in model selection. Sociol Methods Res2004; 33: 261–304.
40.
JonaitisEMJanelidzeSCodyKA, et al.Plasma phosphorylated tau 217 in preclinical Alzheimer's disease. Brain Commun2023; 5: fcad057.
41.
Mattsson-CarlgrenNSalvadóGAshtonNJ, et al.Prediction of longitudinal cognitive decline in preclinical Alzheimer disease using plasma biomarkers. JAMA Neurol2023; 80: 360–369.
42.
ZhangYFerreiraPCLJacobsenE, et al.Association of plasma biomarkers of Alzheimer's disease and related disorders with cognition and cognitive decline: the MYHAT population-based study. Alzheimers Dement2024; 20: 4199–4211.
43.
Jauregi-ZinkunegiAWRERebeccaEL, et al.Associations between the logical memory test story recall metrics and plasma biomarkers for Alzheimer’s disease in individuals free of dementia. Clin Neuropsychol2026; 40: 146–165.
44.
SemenzaC. The neuropsychology of proper names. Mind Lang2009; 24: 347–369.
45.
HanleyJR. Why are names of people associated with so many phonological retrieval failures?Psychon Bull Rev2011; 18: 612–617.
46.
SalthouseTAMandellAR. Do age-related increases in tip-of-the-tongue experiences signify episodic memory impairments?Psychol Sci2013; 24: 2489–2497.
47.
PelamattiGPascottoMSemenzaC. Verbal free recall in high altitude: proper names vs common names. Cortex2003; 39: 97–103.
48.
BrunoDMuellerKDBetthauserT, et al.Serial position effects in the Logical Memory Test: loss of primacy predicts amyloid positivity. J Neuropsychol2021; 15: 448–461.
49.
SundermannEEBiegonARubinLH, et al.Does the female advantage in verbal memory contribute to underestimating Alzheimer's disease pathology in women versus men?J Alzheimers Dis2017; 56: 947–957.
50.
ChapmanRMMapstoneMGardnerMN, et al.Women have farther to fall: gender differences between normal elderly and Alzheimer's disease in verbal memory engender better detection of Alzheimer's disease in women. J Int Neuropsychol Soc2011; 17: 654–662.
51.
SperlingRAJohnsonKADoraiswamyPM, et al.Amyloid deposition detected with florbetapir F 18 ((18)F-AV-45) is related to lower episodic memory performance in clinically normal older individuals. Neurobiol Aging2013; 34: 822–831.
52.
PikeKESavageGVillemagneVL, et al.Beta-amyloid imaging and memory in non-demented individuals: evidence for preclinical Alzheimer's disease. Brain2007; 130: 2837–2844.
53.
ForteaJPeguerolesJAlcoleaD, et al.APOE4 Homozygosity represents a distinct genetic form of Alzheimer’s disease. Nat Med2024; 30: 1284–1291.
54.
FokuohEXiaoDFangW, et al.Longitudinal analysis of APOE-ɛ4 genotype with the logical memory delayed recall score in Alzheimer's disease. J Genet2021; 100: 60.
55.
MuellerKDDuLBrunoD, et al.Item-level story recall predictors of amyloid-beta in late middle-aged adults at increased risk for Alzheimer's disease. Front Psychol2022; 13: 908651.
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