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.

Keywords: Alzheimer disease; Executive functions; Frontotemporal lobar degeneration; Immediate memory; Neuropsychology; Primary progressive aphasia.

Fig. 1

Schematic diagram illustrating the hypothesized contributing cognitive correlates of total immediate recall during learning trials on a verbal list learning paradigm.

Fig. 2

Total repeated immediate recall performance across demographically-matched diagnostic groups. Note. CVLT-SF T1–T4 = California Verbal Learning Test-short form Trials 1–4; AD = Alzheimer’s disease; lvPPA = logopenic variant primary progressive aphasia; bvFTD = behavioral variant frontotemporal dementia; svPPA = semantic variant primary progressive aphasia; nfvPPA = nonfluent variant primary progressive aphasia.

Fig. 3

Distinct cognitive abilities are associated with CVLT-SF T1-T4 Total Immediate Recall performances both within (a) and across (b) diagnostic groups. Note. (a) The cognitive correlates of immediate recall are highly multidimensional demonstrating relatively largest associations with language processing and among the smallest correlations with visual delayed recall abilities (Benson Figure). (b) Importantly, these cognitive correlates are syndrome-specific; for example, in AD, a highly distributed pattern of cognitive correlates is evidenced, whereas in svPPA, semantic processing is the primary cognitive correlate of immediate recall performances. *Partial r adjusted for age, sex, MMSE. CVLT-SF T1-T4 = California Verbal Learning Test-short form Trials 1–4; AD = Alzheimer’s disease; lvPPA = logopenic variant primary progressive aphasia; bvFTD = behavioral variant frontotemporal dementia; svPPA = semantic variant primary progressive aphasia; nfvPPA = nonfluent variant primary progressive aphasia.

Fig. 4

Distinct neuroanatomic correlates are associated with CVLT-SF T1-T4 Total Immediate Recall Performances both within (a) and across (b) diagnostic groups. Note. (a) The neural correlates of immediate recall are also multifaceted, though demonstrating the largest associations with temporal-parietal regions. (b) However, these neuroanatomic patterns vary highly depending on the clinical syndrome examined; for example, in AD, a largely dispersed pattern of anatomic regions is evidenced, whereas in bvFTD, only frontal regions are associated with immediate recall performances. *Partial r adjusted for age, sex, and total intracranial volumes; CVLT-SF T1-T4 = California Verbal Learning Test – short form Trials 1–4; AD = Alzheimer’s disease; lvPPA = logopenic variant primary progressive aphasia; bvFTD = behavioral variant frontotemporal dementia; svPPA = semantic variant primary progressive aphasia; nfvPPA = nonfluent variant primary progressive aphasia.