Memory

As memory impairment is a defining feature of AD, we will now define some basic concepts, and introduce what has been a object of contention for many years, i.e., the differentiation between recollection and familiarity-based recognition. We also define associative memory, and how different types of associations are related to recollection and familiarity. Finally, we will discuss

A

B

11

neuropsychological deficits in the memory domain in MCI and AD. Memory-related structures and networks will be covered in Section 4.1 (Memory networks), while memory-related neuroimaging studies in MCI and AD patients will be addressed in Section 5.1 (Univarite task fMRI studies in MCI/AD).

1.3.1 Different forms of memory

Memory has traditionally been subdivided into different forms (Dickerson and Eichenbaum 2010). A first dissociation is usually made between declarative memory (also called explicit memory), and implicit (nonconscious) memory. The latter encompasses different types of learning that modify behavior, in terms of performance or choices. One example is procedural memory, which involves learning a sequence of movements or actions. Declarative memory encompasses short-term and long-term memory. The first one is commonly referred to as working memory, and implies the short-term maintenance of information for subsequent manipulation. Long-term declarative memory is then subdivided into episodic and semantic memory. Episodic memory incorporates memories of personal experiences, including events and their context, whereas semantic memory involves factual knowledge without the context of their memorization.

1.3.2 Recollection and familiarity

The retrieval of episodic memories can either occur via recall, i.e., remembering an item or an event, or via recognition, i.e., the ability to decide whether an item had been previously presented. Whereas recall is inherently associative, recognition can either be based on recollection or familiarity according to dual-process models (Eichenbaum, Otto et al. 1994, Aggleton and Brown 1999, Yonelinas 2002, Ranganath 2010). Recollection implies the recognition of an item based on the retrieval of specific contextual details, while familiarity-based recognition is familiarity-based on a “feeling” of memory, without the retrieval of any specific details about the encoding context. However, another model, the “single process account” (Squire, Wixted et al. 2007, Slotnick 2013), speculates that instead of being two qualitatively different processes, recollection and familiarity are quantitatively different, i.e., a weaker memory trace will evoke familiarity, whereas a stronger memory trace will elicit recollection.

12

1.3.3 Associative memory

Associative or relational memory involves remembering relations between items of information, such as pairs of words, or an object and its physical or spatio-temporal characteristics (Achim and Lepage 2005, Troyer, Murphy et al. 2012). It contrasts with item memory, which involves remembering individual items independent of any other information associated with them at acquisition.

Inter-items associations can be formed within the same domain/modality (e.g., sensory), or between different domains/modalities. Within-domain inter-item associations can be represented (i.e., perceived and remembered) as a single entity, if their components are bound together into a single unitized representation (e.g., eyes, nose and mouth of a face). However, this is not necessarily the case, as these associations can simply imply similar kinds of items (e.g., two faces; or a table and a chair). Nonetheless, they are likely to be represented by activity in adjacent and interconnected neurons (Mayes, Montaldi et al. 2007). Between-domain inter-item associations cannot be represented as a single entity; they can bind items coming from different sensory modalities, that are spatially or temporally related. These associations are likely to be represented by activity in distant and weakly connected neurons (Mayes, Montaldi et al. 2007).

Familiarity is thought to occur for item memories, but can also take place for within-domain inter-item associations if they are represented as a single entity. In contrast, recollection processes are necessary for between-domain inter-items associations.

1.3.4 Neuropsychology of memory in MCI/AD

Distinct memory systems are differentially affected by AD. Episodic and semantic memory are both impaired early in the course of the disease, whereas procedural learning may remain unaltered until the late stages (Kaszniak, Wilson et al. 1986, Carlesimo and Oscar-Berman 1992).

Both recall and recognition are affected, in both the verbal and nonverbal domains (Chen, Ratcliff et al. 2001). Delayed recall, in particular, is very accurate in discriminating very mild AD from cognitively normal healthy controls (Welsh, Butters et al. 1991, Tabert, Manly et al. 2006, Sarazin, Berr et al. 2007), and in predicting progression to AD in MCI patients (Devanand, Folz et al. 1997, Arnaiz, Almkvist et al. 2004, Gainotti, Quaranta et al. 2014) and in nondemented elderly individuals (Tierney, Yao et al. 2005).

13

Associative memory is impaired early in the course of AD (Dudas, Clague et al. 2005, Anderson, Ebert et al. 2008, Troyer, Murphy et al. 2008, Troyer, Murphy et al. 2012). It is commonly tested using the paired associates learning task (which consists of memorizing pairs of items), which is sensitive to MCI (de Jager, Milwain et al. 2002) and predictive of future conversion to AD (Fowler, Saling et al. 2002, Blackwell, Sahakian et al. 2004, Ahmed, Mitchell et al. 2008). Many studies show that recollection processes are affected in MCI and AD, but that familiarity-based recognition is spared (Dalla Barba 1997, Westerberg, Paller et al. 2006, Anderson, Ebert et al.

2008, Serra, Bozzali et al. 2010). Other studies have shown that both processes were actually affected in MCI and AD patients (Wolk, Signoff et al. 2008, Algarabel, Escudero et al. 2009, Ally, Gold et al. 2009, Algarabel, Fuentes et al. 2012, van der Meulen, Lederrey et al. 2012, Wolk, Mancuso et al. 2013). Schoemaker and collaborators suggested that “while recollection is broadly affected through all stages of the disease process, familiarity deficits seem to be present only at more advanced stages of cognitive impairment” (Schoemaker, Gauthier et al. 2014). In agreement with this conclusion, Hudon and collaborators reported recollection deficits in both MCI and AD, but familiarity deficits in AD only (Hudon, Belleville et al. 2009).

Semantic memory is also impaired in MCI and AD (Salmon, Butters et al. 1999, Dudas, Clague et al. 2005, Vogel, Gade et al. 2005, Joubert, Felician et al. 2008, Joubert, Brambati et al. 2010) and is predictive of cognitive decline (Howieson, Carlson et al. 2008, Hantke, Nielson et al.

2013) and future progression to AD (Blackwell, Sahakian et al. 2004). Deficits in people naming were found in MCI and AD patients (Greene and Hodges 1996, Thompson, Graham et al. 2002, Estevez-Gonzalez, Garcia-Sanchez et al. 2004, Dudas, Clague et al. 2005, Vogel, Gade et al.

2005, Hodges, Erzinclioglu et al. 2006, Joubert, Felician et al. 2008). Category fluency is also impaired in MCI and AD (Petersen, Smith et al. 1994, Tounsi, Deweer et al. 1999, Vogel, Gade et al. 2005, Adlam, Bozeat et al. 2006, Hodges, Erzinclioglu et al. 2006, Price, Kinsella et al.

2012). Furthermore, it was shown that MCI patients were unable to use semantic information to improve their performance in associative memory (Atienza, Atalaia-Silva et al. 2011). It has been suggested that intentional access to semantic knowledge was impaired before automatic access in the course of AD (Perri, Carlesimo et al. 2003, Duong, Whitehead et al. 2006).