The 12-Word Philadelphia Verbal Learning Test Performances in Older Adults: Brain MRI and Cerebrospinal Fluid Correlates and Regression-Based Normative Data

Abstract

Background/Aims: This study evaluated neuroimaging and biological correlates, psychometric properties, and regression-based normative data of the 12-word Philadelphia Verbal Learning Test (PVLT), a list-learning test. Methods: Vanderbilt Memory and Aging Project participants free of clinical dementia and stroke (n = 230, aged 73 ± 7 years) completed a neuropsychological protocol and brain MRI. A subset (n = 111) underwent lumbar puncture for analysis of Alzheimer’s disease (AD) and axonal integrity cerebrospinal fluid (CSF) biomarkers. Regression models related PVLT indices to MRI and CSF biomarkers adjusting for age, sex, race/ethnicity, education, APOE-ε4 carrier status, cognitive status, and intracranial volume (MRI models). Secondary analyses were restricted to participants with normal cognition (NC; n = 127), from which regression-based normative data were generated. Results: Lower PVLT performances were associated with smaller medial temporal lobe volumes (p < 0.05) and higher CSF tau concentrations (p < 0.04). Among NC, PVLT indices were associated with white matter hyperintensities on MRI and an axonal injury biomarker (CSF neurofilament light; p < 0.03). Conclusion: The PVLT appears sensitive to markers of neurodegeneration, including temporal regions affected by AD. Conversely, in cognitively normal older adults, PVLT performance seems to relate to white matter disease and axonal injury, perhaps reflecting non-AD pathways to cognitive change. Enhanced normative data enrich the clinical utility of this tool.

Associations between cerebrospinal fluid markers and cognition in ageing and dementia: A systematic review

“…; Meeter et al, 2016; Meeter, Vijverberg, et al, 2018; van der Ende et al, 2020). The Gothenburg Mild Cognitive Impairment Study (Bjerke et al, 2009; Brinkmalm et al, 2014; Rolstad, Berg, et al, 2015; Wallin et al, 2016) was used in three studies, the Mayo Clinic Study of Ageing (Mielke, Syrjanen, Blennow, Zetterberg, Skoog, et al, 2019; Mielke, Syrjanen, Blennow, Zetterberg, Vemuri, et al, 2019; Roberts et al, 2008) in two studies, the Vanderbilt Memory and Ageing Project (Gifford et al, 2018; Jefferson et al, 2016; Osborn et al, 2019) in two studies and finally, the University of California San Diego (UCSD) Shiley‐Marcos Alzheimer's Disease Research Center (Galasko et al, 2019; Xiao et al, 2017) in two studies.…”

“…Two studies used SIMOA assays. Of the included 67 studies, only 29 reported the intra‐assay coefficient of variability (CV) (Abu‐Rumeileh et al, 2018; Bartos et al, 2011; Bendlin et al, 2012; Bjerke et al, 2009; Brinkmalm et al, 2014; Casaletto et al, 2017; Chatterjee, Del Campo, et al, 2018; Dhiman et al, 2020; Gifford et al, 2018; Hellwig et al, 2015; Hoglund et al, 2017; Kirsebom et al, 2018; Kvartsberg, Duits, et al, 2015; Lim et al, 2019; Meeter et al, 2016; Meeter, Gendron, et al, 2018; Meeter et al, 2019; Meeter, Vijverberg, et al, 2018; Mielke, Syrjanen, Blennow, Zetterberg, Vemuri, et al, 2019; Öhrfelt et al, 2019; Osborn et al, 2019; Rolstad, Jakobsson, et al, 2015; Sandelius et al, 2019; Skillback et al, 2014; Teitsdottir et al, 2020; van der Ende et al, 2020; Wellington et al, 2016; Zetterberg et al, 2016) and only 22 reported inter‐assay CVs (Abu‐Rumeileh et al, 2018; Bartos et al, 2011; Bjerke et al, 2009; Brinkmalm et al, 2014; Chatterjee, Del Campo, et al, 2018; Dhiman et al, 2020; Hellwig et al, 2015; Hoglund et al, 2017; Kvartsberg et al, 2015; Meeter et al, 2016; Meeter, Gendron, et al, 2018; Meeter et al, 2019; Meeter, Vijverberg, et al, 2018; Mielke, Syrjanen, Blennow, Zetterberg, Skoog, et al, 2019; Mielke, Syrjanen, Blennow, Zetterberg, Vemuri, et al, 2019; Mouton‐Liger et al, 2020; Rolstad, Jakobsson, et al, 2015; Sandelius et al, 2019; Singh et al, 2016; Teitsdottir et al, 2020; van der Ende et al, 2020); therefore, the repeatability and technical heterogeneity of results was not reported in the majority of studies.…”

“…One study included participants with subjective cognitive impairment (SCI) and showed a significant association with a number of cognitive composite scores in those with a vascular burden (Rolstad, Berg, et al, 2015). Four studies pooled MCI and age‐matched CU samples and most reported a significant association with neuropsychological performance (Gifford et al, 2018; Osborn et al, 2019; Racine et al, 2016), while one reported no associations after controlling for demographics (Mielke, Syrjanen, Blennow, Zetterberg, Vemuri, et al, 2019). Five studies pooled AD, MCI and CU participants, and all reported a significant association with a number of neuropsychological assessments including the MMSE and ADAS‐Cog11(Bos et al, 2019; Dhiman et al, 2020; Mattsson et al, 2016; Mielke, Syrjanen, Blennow, Zetterberg, Skoog, et al, 2019; Teitsdottir et al, 2020).…”

“…Most studies including CU participants reported a significant association between CSF NfL and neuropsychological performance (Aschenbrenner et al, 2020; Gifford et al, 2018; Mielke, Syrjanen, Blennow, Zetterberg, Skoog, et al, 2019; Osborn et al, 2019); however, three reported no significant correlation (Bendlin et al, 2012; Bos et al, 2019; Hoglund et al, 2017). Moreover, studies using the MMSE consistently reported no significant correlation with CSF NfL levels, while most studies using other validated cognitive assessments reported significant results.…”

Visual and Verbal Serial List Learning in Patients with Statistically-Determined Mild Cognitive Impairment

“…Verbal episodic memory was assessed with the 12-word P(r)VLT (Bezdicek et al, 2014; Gifford Liu, Neal, Babicz, et al, 2018), a test constructed and administered consistent with the 9-word P(r)VLT and original 16-word CVLT (Delis et al, 1987). Visual episodic memory was assessed with the BVMT-R (Benedict, 1997).…”