Effective discrimination with the recency ratio between Alzheimer’s disease and dementia with Lewy bodies

16 August 2018

Despite neuropsychological differences between individuals with Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB), overlap in performance has been observed, including analogous scores in memory tests (Rey Auditory Verbal Learning, AVLT; e.g., [1]). All the while, differential diagnosis remains a costly exercise. However, a recent report [2] has shown that several cognitive scores, including some derived from the AVLT, discriminate between AD (n=32, age=72.2 ± 8.3) and DLB (n=29, age=74.7 ± 7.5), with effect sizes (Cohen’s d) ranging from 0.600 (verbal learning) to 0.870 (rotation).

One of the main findings of this report [2] was that recency performance (i.e., memory for items at the end of the list) at trial 1 of the AVLT was better in AD than in DLB (d=0.652), which is consistent with a vast literature on serial position effects in AD (e.g., [3]), including our own work with the recency ratio (Rr) score [4]. The principle of Rr is that since immediate recency tends to be high in AD, only for delayed recency to be usually low, a ratio between these two measures will be higher in individuals with AD than controls, as well as higher in subjects at risk of decline. We therefore expected that Rr would be highly effective in discriminating between AD and DLB by exploiting this principle.

To test our hypothesis, we calculated Rr from the data reported in [2], using this formula: (trial 1 recency + 1) / (delayed trial recency + 1). Our results show that (natural log transformed) Rr is significantly higher in AD than in DLB (t(58)=4.114, p<0.001) and yields the largest effect size (d=1.060) compared to all other measures above. Similarly, the area under the ROC curve is higher for Rr (0.774) than for trial 1 recency alone (0.670).

Additionally, Rr was associated with the Mini-Mental State Exam score in individuals with AD (r=-0.511, p=0.003), but not in individuals with DLB (r=0.113, p=0.560). These results indicate that Rr scores were also sensitive to the degree of generalised cognitive decline in the AD group.

All in all, these findings support the use of Rr as a cognitive measure for the discrimination between AD and DLB. For reference, an Rr score of 3+ yields a positive predictive value for AD (against DLB) of 88%, and a negative predictive value of 61%, in this sample.

Davide Bruno1,*, Cinzia Busse2,3, Annachiara Cagnin2,4
1School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool, UK
2Department of Neurosciences, University of Padua, Padova, Italy
3Neurofarba, University of Florence, Firenze, Italy
4IRCCS San Camillo Hospital Foundation, Venezia, Italy
*Corresponding author: D.Bruno@ljmu.ac.uk

Acknowledgments
No conflicts of interest to disclose.
This research was presented at the International Neuropsychological Society meeting in Prague, July 2018.

References
[1] Perri R, Fadda L, Caltagirone C, Carlesimo GA (2013) Word list and story recall elicit different patterns of memory deficit in patients with Alzheimer's disease, frontotemporal dementia, subcortical ischemic vascular disease, and Lewy body dementia. J Alzheimers Dis 37, 99-107.
[2] Bussè C, Anselmi P, Pompanin S, Zorzi G, Fragiacomo F, Camporese G, Di Bernardo GA, Semenza C, Caffarra P, Cagnin A (2017) Specific verbal memory measures may distinguish Alzheimer’s disease from dementia with Lewy bodies. J Alzheimers Dis 59, 1009-1015.
[3] Carlesimo GA, Sabbadini M, Fadda L, Caltagirone C (1995) Different components in word-list forgetting of pure amnesics, degenerative demented and healthy subjects. Cortex 31, 735-745.
[4] Bruno D, Koscik RL, Woodard JL, Pomara N, Johnson SC (2018) The recency ratio as predictor of early MCI. Int Psychogeriatr, doi: 10.1017/S1041610218000467.

Comments

Submitted by Giovanni Carlesimo, MD PhD on

In their letter to the Editor, Bruno et al. arise the important issue of the distinct neuropsychological features in different forms of dementia. In particular, the investigation of the memory profiles in the differential diagnosis of dementia types is a current topic in consideration of the fact that memory deficits are frequently present in the very early phase of different forms of dementia, when memory complaints may be the unique sign of an incipient dementia. Indeed, in these phases the opportunity to highlight distinct neuropsychological markers may be greatly useful in the diagnostic process [1].

Bruno et al. propose that the study of dementia patients’ recency performance (i.e., the ability to recall items from the final part of a word-list) and in particular the use of recency ratio score (Rr) (i.e., the ratio between immediate and delayed recency score) may furnish an effective measure in distinguishing patients with Alzheimer’s disease (AD), which usually show high immediate recency effect but a very low delayed one [2], from patients with Lewy bodies dementia (DLB). Indeed, they found that the Rr showed high discriminant power in distinguishing AD from DLB patients.

The study of the recency effect in immediate and delayed word list free recall is based on the concept of the very nature of the memory deficits in the various forms of dementia. There is a large consensus that in AD the long-term episodic memory deficit is mainly due to hippocampal pathology, which severely interferes with the consolidation of memory traces; conversely, in DLB it raises from a less severe impairment of hippocampal processes with a contemporary frontal and executive impairment (responsible for inefficient encoding and/or poor strategic retrieval strategies) [3]. The value of the Bruno et al.’s report may be reinforced, but also mitigated, by similar results we recently obtained and now are going to be published in JAD [4]. In this case, we compared the primacy, mid-list, and recency ratios in patients with AD, frontal variant of frontotemporal dementia (fvFTD), DLB, subcortical ischemic vascular dementia (SIVD), and a group of normal controls. Results showed that only the Rr score differentiated AD from other dementia groups; the hierarchical logistic regression analyses showed a high discriminant power of the Rr in differentiating AD from fvFTD patients, with a less accurate (even if still significant) ability in differentiating AD from DLB and SIVD patients. We assumed that the different discrimination power of Rr among AD and the other dementia groups was related to the different mechanisms underlying memory impairments: a pure hippocampal deficit in AD, a prevalent attentional and executive deficit in FTD and a mixed memory profile (i.e., due to both hippocampal and frontal impairment) in DLB and SIVD.

Roberta Perri1, Chiara Stella Turchetta1, Carlo Caltagirone1,2, Giovanni Augusto Carlesimo1,2,*

1Laboratory of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
2Department of Systems Medicine, "Tor Vergata" University, Rome, Italy
*Corresponding author: memolab@hsantalucia.it

Acknowledgments
No conflicts of interest to disclose.

References
[1] Dubois B, Feldman HH, Jacova C, Cummings JL, Dekosky ST, Barberger-Gateau P, Delacourte A, Frisoni G, Fox NC, Galasko D, Gauthier S, Hampel H, Jicha GA, Meguro K, O'Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Sarazin M, de Souza LC, Stern Y, Visser PJ, Scheltens P (2010) Revising the definition of Alzheimer's disease: a new lexicon. Lancet Neurol 9, 1118-1127.
[2] Carlesimo GA, Sabbadini M, Fadda L, Caltagirone C (1995) Different components in word-list forgetting of pure amnesics, degenerative demented and healthy subjects. Cortex 31, 735-45.
[3] Perri R, Fadda L, Caltagirone C, Carlesimo GA (2013) Word list and story recall elicit different patterns of memory deficit in patients with Alzheimer's disease, frontotemporal dementia, subcortical ischemic vascular disease, and Lewy body dementia. J Alzheimers Dis 37, 99-107.
[4] Turchetta CS, Perri R, Fadda L, Caruso G, De Simone MS, Caltagirone C, Carlesimo GA (2018) Forgetting rate on the recency portion of a word list differentiates mild to moderate Alzheimer’s from other forms of dementia. J Alzheimers Dis, in press.