Is “Learning” episodic memory? Distinct cognitive and neuroanatomic correlates of immediate recall during learning trials in neurologically normal aging and neurodegenerative cohorts

Abstract

Although commonly interpreted as a marker of episodic memory during neuropsychological exams, relatively little is known regarding the neurobehavior of “total learning” immediate recall scores. Medial temporal lobes are clearly associated with delayed recall performances, yet immediate recall may necessitate networks beyond traditional episodic memory. We aimed to operationalize cognitive and neuroanatomic correlates of total immediate recall in several aging syndromes. Demographically-matched neurologically normal adults (n=91), individuals with Alzheimer’s disease (n=566), logopenic variant primary progressive aphasia (PPA) (n=34), behavioral variant frontotemporal dementia (n=97), semantic variant PPA (n=71), or nonfluent/agrammatic variant PPA (n=39) completed a neurocognitive battery, including the CVLT-Short Form trials 1–4 Total Immediate Recall; a majority subset also completed a brain MRI. Regressions covaried for age and sex, and MMSE in cognitive and total intracranial volume in neuroanatomic models. Neurologically normal adults demonstrated a heterogeneous pattern of cognitive associations with total immediate recall (executive, speed, delayed recall), such that no singular cognitive or neuroanatomic correlate uniquely predicted performance. Within the clinical cohorts, there were syndrome-specific cognitive and neural associations with total immediate recall; e.g., semantic processing was the strongest cognitive correlate in svPPA (partial r=0.41), while frontal volumes was the only meaningful neural correlate in bvFTD (partial r=0.20). Medial temporal lobes were not independently associated with total immediate recall in any group (ps > 0.05). Multiple neurobehavioral systems are associated with “total learning” immediate recall scores that importantly differ across distinct clinical syndromes. Conventional memory networks may not be sufficient or even importantly contribute to total immediate recall in many syndromes. Interpreting learning scores as equivalent to episodic memory may be erroneous.

Word Meaning Contributes to Free Recall Performance in Supraspan Verbal List-Learning Tests

“…This type of autonoetic strategy did not emerge as a regularly used strategy in our results, leading to the conclusion that the RAVLT seems unable to assess episodic memory to a reasonable degree, which is similar to the conclusion reached by previous authors (Tulving, 1985(Tulving, , 2002Van der Linden, 2004;Desgranges and Eustache, 2011). Consistent with Gavett and Horwitz's assertion that list-learning test interpretation lacks the construct validity to allowed unbiased estimates of episodic memory ability (Gavett and Horwitz, 2012), our results supplement those reported by Casaletto et al (2017), who focused on total immediate recall performance during learning trials and concluded that interpreting learning scores as equivalent to episodic memory may be erroneous. To avoid any confusion regarding the purpose of the RAVLT, and considering its widespread use, we encourage the use of simple terminology, i.e., "(supraspan) verbal memory, " to briefly characterize the RAVLT assessment.…”

Does amnesia specifically predict Alzheimer’s pathology? A neuropathological study

“…Indeed, numerous studies suggested that severe amnesia could be observed in patients with non-AD or mixed AD pathology, such as DLB (Kraybill et al, 2005;Yoshizawa et al, 2013;Salmon et al, 2015), FTLD (Elgren et al, 1993;Grahan et al, 2005;, or to a lesser degree VaD (Jicha et al, 2006;Reed et al, 2007). This last decade, memory impairment was reported in clinicallydefined DLB (Petrova et al, 2015;Molano et al, 2010), in the clinical subtypes of FTLD such as behavioural variant frontotemporal dementia (Hornberger et al, 2010;Bertoux et al, 2014), semantic progressive aphasia (Casaletto et al, 2017), non-fluent progressive aphasia (Ramanan et al, 2016), amyotrophic lateral sclerosis (Mantovan et al, 2003), progressive supranuclear palsy (Kobylecki et al, 2015) as well as in clinically-defined VaD (Mathias & Burke, 2009) although inconsistent findings were reported in this disease due to the variable topography of vascular lesions. Not least of all, severe amnesia is also the main feature of hippocampal sclerosis, often related to aberrant TDP-43 immunohistochemistry (Nelson et al, 2019).…”

Late-Life Physical and Cognitive Activities Independently Contribute to Brain and Cognitive Resilience

“…Table 2 for the specific measures included per domain. The selected neuropsychological measures have been widely published and shown to be sensitive to age-related neurologic processes [28]. For domains with more than one measure, scores were blom rank transformed to achieve normality before conversion into sample-based z-scores.…”