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...ological disease, major psychiatric disorder or alcohol or substance abuse according to criteria from the Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM–IV]; American Psychiatric =-=Association, 1994-=-), serious medical illness (thyroid disorder; renal, hepatic, cardiac, or pulmonary insufficiency; unstable diabetes; uncontrolled high blood pressure; cancer), and chronic use of psychoactive or hypn...

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... least one additional cognitive domain. Standardized neuropsychological tests used to assess impairments in cognitive domains other than declarative memory included the Mini-Mental State Examination (=-=Folstein, Folstein, & McHugh, 1975-=-), the Category Fluency Test (Morris et al., 1989), the Constructions subtest of the CERAD test battery (Morris et al., 1989), Trail Making Test—Parts A and B (Reitan, 1992), and the Boston Naming Tes...

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...ia were included. The two patient groups included 8 individuals (5 women, 3 men) diagnosed with dementia according to DSM–IV diagnostic criteria and probable AD based on research diagnostic criteria (=-=McKhann et al., 1984-=-) and 8 individuals (6 women, 2 men) diagnosed with MCI. All MCI participants were impaired on memory tests, and some had scores on the Boston Naming Test that were not considered normal for age, such...

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...recognition than in forced-choice recognition. The interaction between patient group and test format was not significant, F(1, 14) � 1, � 2 � .003. Response Bias According to signal-detection theory (=-=Green & Swets, 1966-=-; Macmillan & Creelman, 1991), the use of a forced-choice-test format eliminates any response bias, which can be thought of as the nonspecific tendency to endorse stimuli as belonging to one category ...

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...d entorhinal cortex. The major neuropathological markers of AD are amyloid plaques and neurofibrillary tangles (NFTs) found in larger numbers than those observed in brains of nondemented individuals (=-=Braak & Braak, 1991-=-). Recent evidence indicates that NFT density is also greater in MCI than in normal cognitive aging, although differences in the density of amyloid plaques were not observed (Guillozet, Weintraub, Mas...

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...ghtforward comparisons, hit and falsealarm rates for the yes–no test and the hit rate for the forced-choice test were used to calculate estimates of recognition sensitivity (d�) for each participant (=-=Macmillan & Creelman, 1991-=-). Because the calculation of sensitivity requires that raw proportions be transformed into z scores, all observed proportions were corrected by adding 0.5 to each frequency and dividing by N � 1 (whe...

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...ember–know–guess procedure (Gardiner, Java, & RichardsonKlavehn, 1998). Familiarity contributed more to forced-choice than to yes–no recognition. On the other hand, using the remember–know procedure (=-=Tulving, 1985-=-), no differences in the relative contributions of recollection and familiarity were found between yes–no and forced-choice recognition using unrelated targets and foils (Khoe, Kroll, Yonelinas, Dobbi...

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...al patients have sometimes been described with reference to theories postulating that two distinct memory phenomena can contribute to the recognition of past experience, recollection and familiarity (=-=Mandler, 1980-=-; Yonelinas, 2002). Similarly, one can distinguish between item memory, which pertains to an object or stimulus at the focus of attention, and source memory, which pertains to contextual information (...

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...e sometimes been described with reference to theories postulating that two distinct memory phenomena can contribute to the recognition of past experience, recollection and familiarity (Mandler, 1980; =-=Yonelinas, 2002-=-). Similarly, one can distinguish between item memory, which pertains to an object or stimulus at the focus of attention, and source memory, which pertains to contextual information (such as a spatial...

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...not fit DSM–IV criteria for dementia because in neither case was there evidence of a change in functioning in daily living activities. All AD patients had a clinical dementia rating (CDR) of 1 (mild; =-=Morris, 1993-=-), whereas all MCI patients had a CDR of 0 or 0.5. The mean age of the AD patients was 71.9 years (range: 60–86), and the mean age of the MCI patients was 76.4 years (range: 61–84). On average, AD pat...

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...t learning task from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test battery (Morris et al., 1989) and the Logical Memory II subscale of the Wechsler Memory Scale—Revised (=-=Wechsler, 1987-=-). Memory and other test scores were considered abnormal if they fell two standard deviations or more below relevant norms based on age and education. As shown in Table 2, MCI patients generally displ...

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...the Category Fluency Test (Morris et al., 1989), the Constructions subtest of the CERAD test battery (Morris et al., 1989), Trail Making Test—Parts A and B (Reitan, 1992), and the Boston Naming Test (=-=Kaplan, Goodglass, & Weintraub, 1983-=-). As shown in Table 1, each AD patient exhibited significant deficits for age and level of education in at least one cognitive domain other than declarative memory except for AD Patient 8, who was di...

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...han for familiarity. Subsequent memory analyses have revealed that encoding that led to recollection recruited greater hippocampal activity than encoding that led to familiarity without recollection (=-=Davachi, Mitchell, & Wagner, 2003-=-; Ranganath et al., 2004). During test, recognition based on recollection produced greater hippocampal activation compared with recognition based on familiarity (Eldridge, Knowlton, Furmanski, Bookhei...

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...n severity with disease progression (e.g., Morris, 1996). A prodromal stage of AD that typically includes relatively isolated memory impairments has been designated as mild cognitive impairment (MCI; =-=Petersen et al., 2001-=-). Not all patients with MCI develop AD, but all AD patients pass through a prodromal MCIlike stage. MCI is often distinguished from early dementia on the basis of preserved daily living activities. A...

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...nderlying target and foil memory strength distributions are equivalent. However, in recognition memory experiments, this assumption is not typically warranted (e.g., Ratcliff, Sheu, & Gronlund, 1992; =-=Yonelinas, 1994-=-). When the variances of the underlying target and foil distributions are unequal, d� estimates vary with response bias. Specifically, d� estimates increase as the strictness of the response criterion...

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...uring encoding tend to show greater perirhinal activity for items subsequently recognized with familiarity than for items subsequently forgotten (Davachi et al., 2003; Ranganath et al., 2004; but see =-=Henson, Rugg, Shallice, & Dolan, 1999-=-). During retrieval, most studies have failed to find statistically significant perirhinal activity correlated with familiarity (Eldridge et al., 2000; Henson et al., 1999; Yonelinas et al., 2001). Ho...

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... helpful for organizing categories based on similarity and for generalizing to novel stimuli. Memory for information that is common to several similar items is often referred to as gist memory (e.g., =-=Reyna & Brainerd, 1995-=-; Schacter, Norman, & Koutstaal, 1998). When several similar stimuli are encountered, familiarity is better suited to support memory for gist than recollection, but it is important to keep in mind tha...

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...ion (Davachi, Mitchell, & Wagner, 2003; Ranganath et al., 2004). During test, recognition based on recollection produced greater hippocampal activation compared with recognition based on familiarity (=-=Eldridge, Knowlton, Furmanski, Bookheimer, & Engel, 2000-=-; Yonelinas, Hopfinger, Buonocore, Kroll, & Baynes, 2001). There is some evidence that MTC plays a role in familiarity. Perirhinal cortex, in particular, has been implicated in familiarity processing ...

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...ave demonstrated greater recognition deficits following conjoint perirhinal and parahippocampal lesions than following hippocampal or entorhinal lesions (Leonard, Amaral, Squire, & Zola-Morgan, 1995; =-=Zola-Morgan, Squire, Amaral, & Suzuki, 1989-=-; ZolaMorgan, Squire, & Ramus, 1994), consistent with the possibility that perirhinal cortex plays an important role in familiarity. Yet some evidence suggests that multiple MTC regions may be crucial...

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...ed recognition. Specific MTC regions were initially defined in monkey brains, and these regions have subsequently been identified in human brains, although not without some controversy (Amaral, 1999; =-=Insausti et al., 1998-=-). For example, presumptive perirhinal cortex in humans may actually correspond to what has been anatomically defined by some investigators as transentorhinal cortex, which is the site of maximal neur...

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... given that the variances of the underlying target and foil memory strength distributions are equivalent. However, in recognition memory experiments, this assumption is not typically warranted (e.g., =-=Ratcliff, Sheu, & Gronlund, 1992-=-; Yonelinas, 1994). When the variances of the underlying target and foil distributions are unequal, d� estimates vary with response bias. Specifically, d� estimates increase as the strictness of the r...

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...categories based on similarity and for generalizing to novel stimuli. Memory for information that is common to several similar items is often referred to as gist memory (e.g., Reyna & Brainerd, 1995; =-=Schacter, Norman, & Koutstaal, 1998-=-). When several similar stimuli are encountered, familiarity is better suited to support memory for gist than recollection, but it is important to keep in mind that experience with a specific stimulus...

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...ophy has been implicated as a risk factor for the development of AD (Stoub et al., 2005). In addition, significant neuronal loss has been demonstrated in hippocampus and entorhinal cortex in mild AD (=-=Gomez-Isla et al., 1996-=-; West, Coleman, Flood, & Troncoso, 1994) and in entorhinal cortex in MCI (Kordower et al., 2001). The pathology of AD typically includes damage extending beyond medial temporal regions into several r...

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... that perirhinal cortex activity during retrieval was reliably decreased for familiar items compared with unfamiliar items, although these effects were missed in initial analyses for each experiment (=-=Henson, Casino, Herron, Robb, & Rugg, 2003-=-). Additional evidence from other domains also suggests that perirhinal cortex may be a critical structure for familiarity. Singleunit responses within this region decrease as familiarity of an item i...

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...tion (Folstein, Folstein, & McHugh, 1975), the Category Fluency Test (Morris et al., 1989), the Constructions subtest of the CERAD test battery (Morris et al., 1989), Trail Making Test—Parts A and B (=-=Reitan, 1992-=-), and the Boston Naming Test (Kaplan, Goodglass, & Weintraub, 1983). As shown in Table 1, each AD patient exhibited significant deficits for age and level of education in at least one cognitive domai...

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...re, & Ramus, 1994), consistent with the possibility that perirhinal cortex plays an important role in familiarity. Yet some evidence suggests that multiple MTC regions may be crucial for familiarity (=-=Yonelinas et al., 2002-=-), and the possibility that other cortical regions contribute to familiarity (Henson et al., 1999) cannot be ruled out. Neuropathological investigations of AD and MCI have indicated that the earliest ...

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...ot occur without familiarity (Tulving, 1989). Another possibility is that recollection and familiarity are independent, such that items may evoke recollection without necessarily evoking familiarity (=-=Yonelinas, 1999-=-). 193194 WESTERBERG ET AL. Computationally based claims about the kind of processing strategies that underlie recollection and familiarity have been put forward with reference to the Complementary L...

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...erirhinal cortex may be a critical structure for familiarity. Singleunit responses within this region decrease as familiarity of an item increases, conceivably comprising a code for item familiarity (=-=Brown & Xiang, 1998-=-). Also, ablation studies with monkeys have demonstrated greater recognition deficits following conjoint perirhinal and parahippocampal lesions than following hippocampal or entorhinal lesions (Leonar...

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... Mash, & Mesulam, 2003). The distribution of NFTs is primarily limited to the hippocampus and entorhinal cortex in these cases early on and gradually becomes more widespread with disease progression (=-=Delacourte et al., 1999-=-; Mesulam, 1999). Furthermore, NFT density in the medial temporal lobe is strongly correlated with memory dysfunction (Guillozet et al., 2003). A recent study reported significantly higher tangle coun...

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...cal analyses for each MCI and AD patient in our sample. In general, neuropathological investigations of MCI and AD reliably detect medial temporal damage in individuals with these clinical diagnoses (=-=Price & Morris, 1999-=-; Troncoso, Martin, Dal Forno, & Kawas, 1996). Furthermore, the extent of such damage has been shown to vary with the level of memory impairment. For example, Köhler and colleagues (1998) demonstrated...

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...inergic system could account for what is considered to be age-related cognitive change. Significant atrophy in hippocampus and entorhinal cortex in MCI and AD is also evident in structural MRI (e.g., =-=Du et al., 2001-=-; Killiany et al., 1993; Seab et al., 1988). Some findings have suggested that entorhinal atrophy exceeds that of hippocampus in MCI (Pennanen et al., 2004) and AD (Du et al., 2001; but see Du et al.,...

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...IARITY-BASED RECOGNITION IN MCI AND AD 195 temporal damage have found that these patients generally exhibited recognition deficits in both recollection and familiarity (Giovanello & Verfaellie, 2001; =-=Knowlton & Squire, 1995-=-). The findings across these neuropsychological studies are fairly consistent with the notion that hippocampal damage leads to impaired recollection, whereas damage that extends more broadly through t...

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...is minimal. Additional evidence likewise indicates that patients with damage restricted to the hippocampus can show relatively preserved familiarity with impaired recollection (Aggleton et al., 2005; =-=Baddeley, Vargha-Khadem, & Mishkin, 2001-=-; Bastin et al., 2004; Holdstock et al., 2002; Mayes et al., 2004). Studies that have assessed recognition in patients with extensive medialFAMILIARITY-BASED RECOGNITION IN MCI AND AD 195 temporal da...

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...absence of recollection, as in the butcher-on-the-bus phenomenon, whereby an individual in an atypical setting is recognized but disambiguating contextual information is not retrieved (Mandler, 1980; =-=Yovel & Paller, 2004-=-)—but perhaps recollection does not occur without familiarity (Tulving, 1989). Another possibility is that recollection and familiarity are independent, such that items may evoke recollection without ...

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...CI and AD is also evident in structural MRI (e.g., Du et al., 2001; Killiany et al., 1993; Seab et al., 1988). Some findings have suggested that entorhinal atrophy exceeds that of hippocampus in MCI (=-=Pennanen et al., 2004-=-) and AD (Du et al., 2001; but see Du et al., 2004; Xu et al., 2000), and entorhinal atrophy has been implicated as a risk factor for the development of AD (Stoub et al., 2005). In addition, significa...

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...er cognitive impairments in addition to memory or in a single cognitive domain other than memory, with daily living activities relatively preserved (Luis, Loewenstein, Acevedo, Barker, & Duara, 2003; =-=Winblad et al., 2004-=-). Despite the high incidence of memory deficits in MCI, the precise nature of these impairments remains to be elucidated. Carmen E. Westerberg, Ken A. Paller, and Paul J. Reber, Department of Psychol...

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...2004). During test, recognition based on recollection produced greater hippocampal activation compared with recognition based on familiarity (Eldridge, Knowlton, Furmanski, Bookheimer, & Engel, 2000; =-=Yonelinas, Hopfinger, Buonocore, Kroll, & Baynes, 2001-=-). There is some evidence that MTC plays a role in familiarity. Perirhinal cortex, in particular, has been implicated in familiarity processing by some fMRI studies, although others have failed to fin...

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...y. In patients with damage limited to the hippocampus, recall was clearly impaired, but in some patients, item recognition was apparently intact or at least relatively intact (Aggleton & Brown, 1999; =-=Mayes, Holdstock, Isaac, Hunkin, & Roberts, 2002-=-; Vargha-Khadem et al., 1997). These findings have prompted speculation that a hippocampal contribution is necessary for normal performance when memory tasks require recollection, but is not necessary...

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...younger AD patients. For each patient, an informant provided objective information in an interview about daily living activities using the Informant Questionnaire on Cognitive Decline in the Elderly (=-=Jorm, 1994-=-). None of the MCI patients were reported by informants to have any observable changes in usual daily living activities. Memory impairments in MCI and AD patients were quantified using the word-list l...

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... to the hippocampus can show relatively preserved familiarity with impaired recollection (Aggleton et al., 2005; Baddeley, Vargha-Khadem, & Mishkin, 2001; Bastin et al., 2004; Holdstock et al., 2002; =-=Mayes et al., 2004-=-). Studies that have assessed recognition in patients with extensive medialFAMILIARITY-BASED RECOGNITION IN MCI AND AD 195 temporal damage have found that these patients generally exhibited recogniti...

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...as a risk factor for the development of AD (Stoub et al., 2005). In addition, significant neuronal loss has been demonstrated in hippocampus and entorhinal cortex in mild AD (Gomez-Isla et al., 1996; =-=West, Coleman, Flood, & Troncoso, 1994-=-) and in entorhinal cortex in MCI (Kordower et al., 2001). The pathology of AD typically includes damage extending beyond medial temporal regions into several regions of neocortex (Braak & Braak, 1991...

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...The distribution of NFTs is primarily limited to the hippocampus and entorhinal cortex in these cases early on and gradually becomes more widespread with disease progression (Delacourte et al., 1999; =-=Mesulam, 1999-=-). Furthermore, NFT density in the medial temporal lobe is strongly correlated with memory dysfunction (Guillozet et al., 2003). A recent study reported significantly higher tangle counts in the nucle...

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...uals (Braak & Braak, 1991). Recent evidence indicates that NFT density is also greater in MCI than in normal cognitive aging, although differences in the density of amyloid plaques were not observed (=-=Guillozet, Weintraub, Mash, & Mesulam, 2003-=-). The distribution of NFTs is primarily limited to the hippocampus and entorhinal cortex in these cases early on and gradually becomes more widespread with disease progression (Delacourte et al., 199...

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...uld account for what is considered to be age-related cognitive change. Significant atrophy in hippocampus and entorhinal cortex in MCI and AD is also evident in structural MRI (e.g., Du et al., 2001; =-=Killiany et al., 1993-=-; Seab et al., 1988). Some findings have suggested that entorhinal atrophy exceeds that of hippocampus in MCI (Pennanen et al., 2004) and AD (Du et al., 2001; but see Du et al., 2004; Xu et al., 2000)...

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...age extending beyond medial temporal regions into several regions of neocortex (Braak & Braak, 1991). Cortical hypometabolism (e.g., de Leon et al., 1983; Foster et al., 1984; Friedland et al., 1989; =-=Grady et al., 1988-=-; Ibáñez et al., 1998) and NFTs (Braak & Braak, 1991; Delacourte et al., 1999) can also be found throughout temporal, parietal, and frontal cortex in individuals with AD. Understanding the precise nat...

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...ion, significant neuronal loss has been demonstrated in hippocampus and entorhinal cortex in mild AD (Gomez-Isla et al., 1996; West, Coleman, Flood, & Troncoso, 1994) and in entorhinal cortex in MCI (=-=Kordower et al., 2001-=-). The pathology of AD typically includes damage extending beyond medial temporal regions into several regions of neocortex (Braak & Braak, 1991). Cortical hypometabolism (e.g., de Leon et al., 1983; ...

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...ts, whereas damage to hippocampus and entorhinal cortex could impair yes–no recognition in both AD and MCI. In addition to memory deficits, individuals with AD also exhibit perceptual deficits (e.g., =-=Cronin-Golomb et al., 1991-=-). Visuoperceptual deficits may have reduced the ability of AD patients to effectively encode and store sufficient detail to successfully complete the recognition tasks in this experiment. These perce...

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... medial temporal regions into several regions of neocortex (Braak & Braak, 1991). Cortical hypometabolism (e.g., de Leon et al., 1983; Foster et al., 1984; Friedland et al., 1989; Grady et al., 1988; =-=Ibáñez et al., 1998-=-) and NFTs (Braak & Braak, 1991; Delacourte et al., 1999) can also be found throughout temporal, parietal, and frontal cortex in individuals with AD. Understanding the precise nature of memory impairm...

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...n one study, patients with AD showed some ability to discriminate previously presented words from novel words but performed at a chance level when asked to identify the color of each recognized word (=-=Tendolkar et al., 1999-=-). Such dissociations may highlight systematic differences in the nature of information-processing dysfunction. Memory dissociations in neurological patients have sometimes been described with referen...

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...ith this prediction, recent evidence indicates that patients with AD are impaired at yes–no recognition for categorized color photographs (Budson et al., 2003) and perceptually similar novel objects (=-=Budson, Desikan, Daffner, & Schacter, 2001-=-). If intact hippocampal and entorhinal tissue is critical for familiarity, then AD and MCI patients should also show impairments on the forced-choice test. However, if intact hippocampal and entorhin...

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...know procedure (Tulving, 1985), no differences in the relative contributions of recollection and familiarity were found between yes–no and forced-choice recognition using unrelated targets and foils (=-=Khoe, Kroll, Yonelinas, Dobbins, & Knight, 2000-=-). These results suggest that the utility of familiarity is greater in forcedchoice recognition than in yes–no recognition only when targets and foils are similar. Recent evidence from neuropsychologi...

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...that recollection may be more disrupted than familiarity in AD (Bartok et al., 1997; Budson, Daffner, Desikan, & Schacter, 2000; Dalla Barba, 1997; Gallo, Sullivan, Daffner, Schacter, & Budson, 2004; =-=Knight, 1998-=-; Koivisto, Portin, Seinela, & Rinne, 1998; Tendolkar et al., 1999). No previous studies have examined the efficacy of recollection and familiarity in MCI, and our findings reveal something quite rema...

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..., 1998). Also, ablation studies with monkeys have demonstrated greater recognition deficits following conjoint perirhinal and parahippocampal lesions than following hippocampal or entorhinal lesions (=-=Leonard, Amaral, Squire, & Zola-Morgan, 1995-=-; Zola-Morgan, Squire, Amaral, & Suzuki, 1989; ZolaMorgan, Squire, & Ramus, 1994), consistent with the possibility that perirhinal cortex plays an important role in familiarity. Yet some evidence sugg...

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...f hippocampus in MCI (Pennanen et al., 2004) and AD (Du et al., 2001; but see Du et al., 2004; Xu et al., 2000), and entorhinal atrophy has been implicated as a risk factor for the development of AD (=-=Stoub et al., 2005-=-). In addition, significant neuronal loss has been demonstrated in hippocampus and entorhinal cortex in mild AD (Gomez-Isla et al., 1996; West, Coleman, Flood, & Troncoso, 1994) and in entorhinal cort...

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...01) although recent reports using detailed informant interviews have suggested that nondemented individuals with mild cognitive deficits may have some difficulty with certain daily living activities (=-=Artero, Touchon, & Ritchie, 2001-=-; Tabert et al., 2002). Furthermore, a diagnosis of MCI can be made on the basis of a variety of cognitive deficits, and further classification of MCI into various subtypes is now emerging (Petersen, ...

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...nt results are consistent with previous suggestions that recollection may be more disrupted than familiarity in AD (Bartok et al., 1997; Budson, Daffner, Desikan, & Schacter, 2000; Dalla Barba, 1997; =-=Gallo, Sullivan, Daffner, Schacter, & Budson, 2004-=-; Knight, 1998; Koivisto, Portin, Seinela, & Rinne, 1998; Tendolkar et al., 1999). No previous studies have examined the efficacy of recollection and familiarity in MCI, and our findings reveal someth...

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...rity.202 WESTERBERG ET AL. functional consequences. Indeed, volumetric MRI results indicate that perirhinal cortex exhibits significant atrophy in AD, although not as severe as in entorhinal cortex (=-=Juottonen et al., 1998-=-). Some perirhinal atrophy may thus be present in MCI patients as well, but perhaps it is insufficient to impair familiarity-based recognition. Specific MTC regions were initially defined in monkey br...

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...ion may be more disrupted than familiarity in AD (Bartok et al., 1997; Budson, Daffner, Desikan, & Schacter, 2000; Dalla Barba, 1997; Gallo, Sullivan, Daffner, Schacter, & Budson, 2004; Knight, 1998; =-=Koivisto, Portin, Seinela, & Rinne, 1998-=-; Tendolkar et al., 1999). No previous studies have examined the efficacy of recollection and familiarity in MCI, and our findings reveal something quite remarkable. Although recollection was impaired...

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...variances of the underlying target and foil distributions are unequal, d� estimates vary with response bias. Specifically, d� estimates increase as the strictness of the response criterion increases (=-=Kroll, Yonelinas, Dobbins, & Frederick, 2002-=-). Thus, it is possible that differences in yes–no d� calculated for Figure 3. Recognition impairment estimates (M control d� �patient d�) plotted as a function of test format (yes–no or forced choice...

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...memory deficits leading to AD, the category of MCI may encompass more than one disease process, perhaps including factors related to cerebrovascular disease (Galluzzi, Sheu, Zanetti, & Frisoni, 2005; =-=Roman et al., 2004-=-), and there may be additional MCI subtypes yet to be described. In conclusion, the present results indicate that in patients with diagnoses of AD or MCI, familiarity is relatively preserved compared ...

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...rea that can be referred to as medial temporal cortex (MTC). The anterior portion of MTC includes entorhinal and perirhinal cortices, and the posterior portion of MTC includes parahippocampal cortex (=-=Amaral, 1999-=-). Evidence from functional magnetic resonance imaging (fMRI) also indicates that the hippocampus may be more critical for recollection than for familiarity. Subsequent memory analyses have revealed t...

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... al., 2001; Killiany et al., 1993; Seab et al., 1988). Some findings have suggested that entorhinal atrophy exceeds that of hippocampus in MCI (Pennanen et al., 2004) and AD (Du et al., 2001; but see =-=Du et al., 2004-=-; Xu et al., 2000), and entorhinal atrophy has been implicated as a risk factor for the development of AD (Stoub et al., 2005). In addition, significant neuronal loss has been demonstrated in hippocam...

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...counts have pointed out that MCI can occur with other cognitive impairments in addition to memory or in a single cognitive domain other than memory, with daily living activities relatively preserved (=-=Luis, Loewenstein, Acevedo, Barker, & Duara, 2003-=-; Winblad et al., 2004). Despite the high incidence of memory deficits in MCI, the precise nature of these impairments remains to be elucidated. Carmen E. Westerberg, Ken A. Paller, and Paul J. Reber,...

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...detailed informant interviews have suggested that nondemented individuals with mild cognitive deficits may have some difficulty with certain daily living activities (Artero, Touchon, & Ritchie, 2001; =-=Tabert et al., 2002-=-). Furthermore, a diagnosis of MCI can be made on the basis of a variety of cognitive deficits, and further classification of MCI into various subtypes is now emerging (Petersen, 2004). Although, in t...

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...dual in an atypical setting is recognized but disambiguating contextual information is not retrieved (Mandler, 1980; Yovel & Paller, 2004)—but perhaps recollection does not occur without familiarity (=-=Tulving, 1989-=-). Another possibility is that recollection and familiarity are independent, such that items may evoke recollection without necessarily evoking familiarity (Yonelinas, 1999). 193194 WESTERBERG ET AL....

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... in the present study, we have emphasized memory deficits leading to AD, the category of MCI may encompass more than one disease process, perhaps including factors related to cerebrovascular disease (=-=Galluzzi, Sheu, Zanetti, & Frisoni, 2005-=-; Roman et al., 2004), and there may be additional MCI subtypes yet to be described. In conclusion, the present results indicate that in patients with diagnoses of AD or MCI, familiarity is relatively...

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...nts with extensive medialFAMILIARITY-BASED RECOGNITION IN MCI AND AD 195 temporal damage have found that these patients generally exhibited recognition deficits in both recollection and familiarity (=-=Giovanello & Verfaellie, 2001-=-; Knowlton & Squire, 1995). The findings across these neuropsychological studies are fairly consistent with the notion that hippocampal damage leads to impaired recollection, whereas damage that exten...

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...ollection and familiarity. In patients with damage limited to the hippocampus, recall was clearly impaired, but in some patients, item recognition was apparently intact or at least relatively intact (=-=Aggleton & Brown, 1999-=-; Mayes, Holdstock, Isaac, Hunkin, & Roberts, 2002; Vargha-Khadem et al., 1997). These findings have prompted speculation that a hippocampal contribution is necessary for normal performance when memor...

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... would result in yes–no recognition impairments. Consistent with this prediction, recent evidence indicates that patients with AD are impaired at yes–no recognition for categorized color photographs (=-=Budson et al., 2003-=-) and perceptually similar novel objects (Budson, Desikan, Daffner, & Schacter, 2001). If intact hippocampal and entorhinal tissue is critical for familiarity, then AD and MCI patients should also sho...

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...tion, familiarity Alzheimer’s disease (AD) is associated with deficits in several cognitive domains, including episodic memory, and these deficits increase in severity with disease progression (e.g., =-=Morris, 1996-=-). A prodromal stage of AD that typically includes relatively isolated memory impairments has been designated as mild cognitive impairment (MCI; Petersen et al., 2001). Not all patients with MCI devel...

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... in the yes–no recognition test than in the forcedchoice recognition test. The present results are consistent with previous suggestions that recollection may be more disrupted than familiarity in AD (=-=Bartok et al., 1997-=-; Budson, Daffner, Desikan, & Schacter, 2000; Dalla Barba, 1997; Gallo, Sullivan, Daffner, Schacter, & Budson, 2004; Knight, 1998; Koivisto, Portin, Seinela, & Rinne, 1998; Tendolkar et al., 1999). No...

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... considered to be age-related cognitive change. Significant atrophy in hippocampus and entorhinal cortex in MCI and AD is also evident in structural MRI (e.g., Du et al., 2001; Killiany et al., 1993; =-=Seab et al., 1988-=-). Some findings have suggested that entorhinal atrophy exceeds that of hippocampus in MCI (Pennanen et al., 2004) and AD (Du et al., 2001; but see Du et al., 2004; Xu et al., 2000), and entorhinal at...

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...D typically includes damage extending beyond medial temporal regions into several regions of neocortex (Braak & Braak, 1991). Cortical hypometabolism (e.g., de Leon et al., 1983; Foster et al., 1984; =-=Friedland et al., 1989-=-; Grady et al., 1988; Ibáñez et al., 1998) and NFTs (Braak & Braak, 1991; Delacourte et al., 1999) can also be found throughout temporal, parietal, and frontal cortex in individuals with AD. Understan...

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...who were followed longitudinally and who, prior to death, had shown evidence of a change from cognitively normal to MCI compared with cognitively normal individuals who remained that way until death (=-=Mesulam, Shaw, Mash, & Weintraub, 2004-=-). It was suggested that this early involvement of the cholinergic system could account for what is considered to be age-related cognitive change. Significant atrophy in hippocampus and entorhinal cor...

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...d on memory tests, and some had scores on the Boston Naming Test that were not considered normal for age, such that they fell into the category of amnestic-multiple domain MCI (Petersen et al., 2001; =-=Petersen, 2004-=-). Cutoff scores for abnormality on each neuropsychological test were two standard deviations below the mean score for the relevant age and education group (wherever available). This highly conservati...