Evidence from patients with amnesia suggests that recognition memory span tasks engage both long-term memory (i.e., secondary memory) processes mediated by the diencephalic-medial temporal lobe memory system and working memory processes mediated by fronto-striatal systems. Thus, the recognition memory span task may be particularly effective for detecting memory deficits in disorders that disrupt both memory systems. The presence of unique pathology in fronto-striatal circuits in Dementia with Lewy Bodies (DLB) compared to AD suggests that performance on the recognition memory span task might be differentially affected in the two disorders even though they have quantitatively similar deficits in secondary memory. In the present study, patients with autopsy-confirmed DLB or AD, and Normal Control (NC) participants, were tested on separate recognition memory span tasks that required them to retain increasing amounts of verbal, spatial, or visual object (i.e., faces) information across trials. Results showed that recognition memory spans for verbal and spatial stimuli, but not face stimuli, were lower in patients with DLB than in those with AD, and more impaired relative to NC performance. This was despite similar deficits in the two patient groups on independent measures of secondary memory such as the total number of words recalled from long-term storage on the Buschke Selective Reminding Test. The disproportionate vulnerability of recognition memory span task performance in DLB compared to AD may be due to greater fronto-striatal involvement in DLB and a corresponding decrement in cooperative interaction between working memory and secondary memory processes. Assessment of recognition memory span may contribute to the ability to distinguish between DLB and AD relatively early in the course of disease.

Approximately 30% of healthy persons aged over 75 years show Abeta deposition at autopsy. It is postulated that this represents preclinical Alzheimer's disease (AD). We evaluated the relationship between Abeta burden as assessed by PiB PET and cognitive decline in a well-characterized, non-demented, elderly cohort. PiB PET studies and cognitive tests were performed on 34 elderly participants (age 73+/-6) from the longitudinal Melbourne Healthy Aging Study (MHAS). Subjects were classified as being cognitively 'stable' or 'declining' by an independent behavioural neurologist based on clinical assessment and serial word-list recall scores from the preceding 6-10 years. Decline was calculated from the slope of the word-list recall scores. Abeta burden was quantified using Standardized Uptake Value normalized to cerebellar cortex. Ten subjects were clinically classified as declining. At the time of the PET scans, three of the declining subjects had mild cognitive impairment, one had AD, and six were declining but remained within the normal range for age on cognitive tests. Declining subjects were much more likely to show cortical PiB binding than stable subjects (70% vs. 17%, respectively). Neocortical Abeta burden correlated with word-list recall slopes (r=-0.78) and memory function (r=-0.85) in the declining group. No correlations were observed in the stable group. Abeta burden correlated with incident memory impairment and the rate of memory decline in the non-demented ageing population. These observations suggest that neither memory decline nor Abeta deposition are part of normal ageing and likely represent preclinical AD. Further longitudinal observations are required to confirm this hypothesis.

Attentional selection, i.e. filtering out of irrelevant sensory input and information storage are two crucial components of working memory (WM). It has been proposed that the two processes are mediated by different neurotransmitters, namely acetylcholine for attentional selection and dopamine for memory storage. However, this hypothesis has been challenged by others, who for example linked a lack in dopamine levels in the brain to filtering deficits. Here we tested the above mentioned hypothesis in two patient cohorts which either served as a proxy for a cholinergic or a dopaminergic deficit. The first group comprised 18 patients with amnestic mild cognitive impairment (aMCI), the second 22 patients with Parkinson׳s disease (PD). The two groups did not differ regarding their overall cognitive abilities. Both patient groups as well as a control group without neurological deficits (n=25) performed a visuo-spatial working memory task in which both the necessity to filter out irrelevant information and memory load, i.e. the number of items to be held in memory, were manipulated. In accordance with the primary hypothesis, aMCI patients displayed problems with filtering, i.e., were especially impaired when the task required ignoring distracting stimuli. PD patients on the other hand showed difficulties when memory load was increased suggesting that they mainly suffered from a storage deficit. In sum, this study underlines how the investigation of neurologic patients with a presumed neurotransmitter deficit can aid to clarify these neurotransmitters׳ contribution to specific cognitive functions.

Amnestic mild cognitive impairment (aMCI) has been conceptualized as a transitional stage between healthy aging and Alzheimer's disease (AD). Therefore, understanding which aspects of memory are impaired and which remain relatively intact in these patients can be useful in determining who will ultimately go on to develop AD, and subsequently designing interventions to help patients live more engaged and independent lives. The dual-process model posits that recognition memory decisions can rely on either familiarity or recollection. Whereas research is fairly consistent in showing impaired recollection in patients with aMCI, the results have been mixed regarding familiarity. A noted difference between these studies investigating familiarity has been stimulus type. The goal of the current investigation was to use high-density event-related potentials (ERPs) to help elucidate the neural correlates of recognition decisions in patients with aMCI for words and pictures. We also hoped to help answer the question of whether patients can rely on familiarity to support successful recognition. Patients and controls participated in separate recognition memory tests of words and pictures while ERPs were recorded during retrieval. Results showed that ERP components typically associated with familiarity and retrieval monitoring were similar between groups for pictures. However, these components were diminished in the patient group for words. Based on recent work, the authors discuss the possibility that implicit conceptual priming could have contributed to the enhanced ERP correlate of familiarity. Further, the authors address the possibility that enhanced retrieval monitoring may be needed to modulate increased familiarity engendered by pictures.

The aim of our study was to quantify the structural integrity of the long association fibre tracts in early Alzheimer's disease (AD) and to correlate the findings with the cognitive performance of the patients. We conducted region-of-interest-based analyses of color-coded diffusion-tensor imaging in 12 patients with early AD (age 69.8+/-8.0 years; MMSE 25.3+/-1.8) and 16 age- and education-matched healthy controls. Early AD patients showed significantly decreased fractional anisotropy (FA) of the cingulate bundles and the inferior fronto-occipital fascicles bilaterally, whereas FA values of the superior longitudinal fascicles (second division) did not differ significantly between patients and controls. Neuropsychological performance of patients in the verbal episodic memory test domain correlated significantly with disturbances of left cingulate fibre tract integrity. Reduced left cingulate bundle integrity was most strongly correlated with impaired performance in a verbal recognition task (Spearman's rho=0.81, P=0.001). Moreover, Boston naming test performance also correlated with the left cingulate bundle integrity (Spearman's rho=0.71, P=0.009). These findings suggest substantial disturbances of the structural connectivity within long association fibre tracts, especially the cingulate bundles and the inferior fronto-occipital fascicles, in early AD and highlight the important role of the cingulate bundles in verbal recognition.

We assessed the ability of two groups of patients with mild Alzheimer's disease (AD) and two groups of older adults to monitor the likely accuracy of recognition judgments and source identification judgments about who spoke something earlier. Alzheimer's patients showed worse performance on both memory judgments and were less able to monitor with confidence ratings the likely accuracy of both kinds of memory judgments, as compared to a group of older adults who experienced the identical study and test conditions. Critically, however, when memory performance was made comparable between the AD patients and the older adults (e.g., by giving AD patients extra exposures to the study materials), AD patients were still greatly impaired at monitoring the likely accuracy of their recognition and source judgments. This result indicates that the monitoring impairment in AD patients is actually worse than their memory impairment, as otherwise there would have been no differences between the two groups in monitoring performance when there were no differences in accuracy. We discuss the brain correlates of this memory-monitoring deficit and also propose a Remembrance-Evaluation model of memory-monitoring.

In this article we aimed to assess how Alzheimer's disease (AD), which is neurodegenerative, affects the linguistic performance of early, high-proficient bilinguals in their two languages. To this end, we compared the Picture Naming and Word Translation performances of two groups of AD patients varying in disease progression (Mild and Moderate) with that of bilingual individuals diagnosed with mild cognitive impairment (MCI). The results revealed that the linguistic deterioration caused by AD affected the two languages similarly. We also found that cognate status and word frequency were two major determinants of language performance in all three groups of participants. These results are consistent with the notion of a common neural substrate recruited to represent and process the two languages of high-proficient bilinguals.

Understanding how memory breaks down in the earliest stages of Alzheimer's disease (AD) process has significant implications, both clinically and with respect to intervention development. Previous work has highlighted a robust picture superiority effect in patients with amnestic mild cognitive impairment (aMCI). However, it remains unclear as to how pictures improve memory compared to words in this patient population. In the current study, we utilized receiver operating characteristic (ROC) curves to obtain estimates of familiarity and recollection for pictures and words in patients with aMCI and healthy older controls. Analysis of accuracy shows that even when performance is matched between pictures and words in the healthy control group, patients with aMCI continue to show a significant picture superiority effect. The results of the ROC analysis showed that patients demonstrated significantly impaired recollection and familiarity for words compared controls. In contrast, patients with aMCI demonstrated impaired recollection, but intact familiarity for pictures, compared to controls. Based on previous work from our lab, we speculate that patients can utilize the rich conceptual information provided by pictures to enhance familiarity, and perceptual information may allow for post-retrieval monitoring or verification of the enhanced sense of familiarity. Alternatively, the combination of enhanced conceptual and perceptual fluency of the test item might drive a stronger or more robust sense of familiarity that can be accurately attributed to a studied item.

Prior work suggests that patients with mild Alzheimer's disease (AD) often base their recognition memory decisions on familiarity. It has been argued that conceptual fluency may play an important role in the feeling of familiarity. In the present study we measured the effect of conceptual fluency manipulations on recognition judgments of patients with mild AD and older adult controls. "Easy" and "hard" test conditions were created by manipulating encoding depth and list length to yield high and low discrimination, respectively. When the two participant groups performed identical procedures, AD patients displayed lower discrimination and greater reliance on fluency cues than controls. However, when the discrimination of older adult controls was decreased to the level of AD patients by use of a shallow encoding task, we found that controls reliance on fluency did not statistically differ from AD patients. Furthermore, we found that increasing discrimination using shorter study lists resulted in AD patients decreasing their reliance on fluency cues to a similar extent as controls. These findings support the notion that patients with AD are able to attribute conceptual fluency to prior experience. In addition, these findings suggest that discrimination and reliance on fluency cues may be inversely related in both AD patients and older adult controls.

Decisions under ambiguity and decisions under risk are crucial types of decision making in daily living at any age. This is the first study assessing these two types of decisions in patients with mild dementia of Alzheimer's type (DAT) by means of the Iowa Gambling Task (IGT) and a newly developed, Probability-Associated Gambling (PAG) task. While rules for gains and losses are implicit in the IGT, in the PAG task rules are explicit and winning probabilities, which change from trial to trial, can be estimated. Results of the IGT indicated that DAT patients made more disadvantageous decisions than healthy controls. Patients also shifted more frequently among decks, i.e. under ambiguity decisions were taken randomly and no advantageous strategy was established over time by DAT patients. Thus, not only actual choices but also development of advantageous strategies may be revealing about decision making in the IGT. Compared to controls, patients demonstrated less advantageous choices in the PAG task as well. They gambled more often in the low winning probabilities and less frequently in the high probabilities than healthy participants. Patients' performance on both tasks correlated with measures of executive functions. Findings of the present investigation are consistent with the early pathological cerebral changes and related (cognitive, emotional) deficits reported for DAT. As suggested by our study, decisions under ambiguity as well as decisions under risk are impaired in mild DAT. It may thus be expected that patients with mild DAT have difficulties in taking decisions in every-day life situations, both in cases of ambiguity (information on probability is missing or conflicting, and the expected utility of the different options is incalculable) and in cases of risk (outcomes can be predicted by well-defined or estimable probabilities).

Decision-making in mild dementia of Alzheimer's type (DAT) was assessed in a gambling task with stable and explicit rules [Game of Dice Task; Brand, M., Labudda, K., Kalbe, E., Hilker, R., Emmans, D., Fuchs, G., et al. (2004). Decision-making impairments in patients with Parkinson's disease. Behavioural Neurology, 15, 77-85]. DAT patients in an early stage of the disease chose safe alternatives as frequently as healthy elderly persons and did not show risky behaviour as has been reported for other neurological patient groups. However, a more detailed analysis disclosed important differences between DAT and healthy elderly. Compared to healthy controls, DAT patients shifted more frequently between safe and risky alternatives and showed less consistent response patterns. Frequent changes between strategies indicate that decisions were taken randomly, that no advantageous strategy was established and that no consistent response pattern was developed over time. As regards performance changes over the task, healthy participants had a stronger tendency towards safe and advantageous responses than DAT patients. While healthy controls showed learning as the task proceeded, DAT patients did not adapt their strategies. The proportion of "consistently safe responders" was significantly higher in the control group than in the DAT group. Analysis of reaction times indicated that differences in response behaviour were not due to fast and impulsive decision taking in the DAT group. DAT patients' response pattern may be attributed to deficits in learning and in executive functions. The frequency of changes between safe and risky choices proved to be a fair predictor for the distinction between mild DAT and healthy aging.

Neuropsychiatric symptoms seen in Alzheimer's disease (AD) are not simply a consequence of neurodegeneration, but probably result from differential neurotransmitter alterations, which some patients are more at risk of than others. Therefore, the hypothesis of this study is that an imbalance between the cholinergic and serotonergic systems is related to cognitive symptoms and psychological syndromes of dementia (BPSD) in patients with AD. Cholinergic and serotonergic functions were assessed in post-mortem frontal and temporal cortex from 22 AD patients who had been prospectively assessed with the Mini-Mental State examination (MMSE) for cognitive impairment and with the Present Behavioral Examination (PBE) for BPSD including aggressive behavior, overactivity, depression and psychosis. Not only cholinergic deficits, but also the cholinacetyltransferase/serotonin ratio significantly correlated with final MMSE score both in frontal and temporal cortex. In addition, decreases in cholinergic function correlated with the aggressive behavior factor, supporting a dual role for the cholinergic system in cognitive and non-cognitive disturbances associated to AD. The serotonergic system showed a significant correlation with overactivity and psychosis. The ratio of serotonin to acetylcholinesterase levels was also correlated with the psychotic factor at least in women. It is concluded that an imbalance between cholinergic-serotonergic systems may be responsible for the cognitive impairment associated to AD. Moreover, the major findings of this study are the relationships between neurochemical markers of both cholinergic and serotonergic systems and non-cognitive behavioral disturbances in patients with dementia.

There has been much recent investigation into the role of parietal cortex in memory retrieval. Proposed hypotheses include attention to internal memorial representations, an episodic working memory-type buffer, and an accumulator of retrieved memorial information. The current investigation used event-related potentials (ERPs) to test the episodic buffer hypothesis, and to assess the memorial contribution of parietal cortex in younger and older adults, and in patients with circumscribed lateral parietal lesions. In a standard recognition memory paradigm, subjects studied color pictures of common objects. One-third of the test items were presented in the same viewpoint as the study phase, one-third were presented in a 90 degrees rotated viewpoint, and one-third were presented in a noncanonical viewpoint. Conflicting with the episodic buffer hypothesis, results revealed that the duration of the parietal old/new effect was longest for the canonical condition and shortest for the noncanonical condition. Results also revealed that older adults demonstrated a diminished parietal old/new effect relative to younger adults. Consistent with previous data reported by Simons et al., patients with lateral parietal lesions showed no behavioral impairment compared to controls. Behavioral and ERP data from parietal lesion patients are presented and discussed. From these results, the authors speculate that the parietal old/new effect may be the neural correlate of an individual's subjective recollective experience.

The basal ganglia are critically involved in language control (LC) processes, allowing a bilingual to utter correctly in one language without interference from the non-requested language. It has been hypothesized that the neural mechanism of LC closely resembles domain-general executive control (EC). The purpose of the present study is to investigate the integrity of bilingual LC and its overlap with domain-general EC in a clinical population such as individuals with Parkinson's disease (PD), notoriously associated with structural damage in the basal ganglia. We approach these issues in two ways. First, we employed a language switching task to investigate the integrity of LC in a group of Catalan-Spanish bilingual individuals with PD, as compared to a group of matched healthy controls. Second, to test the relationship between domain-general EC and LC we compared the performances of individuals with PD and healthy controls also in a non-linguistic switching task. We highlight that, compared to controls, individuals with PD report decreased processing speed, less accuracy and larger switching costs in terms of RT and errors in the language switching task, whereas in the non-linguistic switching task PD patients showed only increased switching cost in terms of errors. However, we report a positive correlation between the magnitudes of linguistic and non-linguistic mixing costs in individuals with PD. Taken together, these results support the notion of a critical role of the basal ganglia and connected structures in LC, and suggest a possible link between LC and domain-general EC.

Retrograde memory decline in Alzheimer's disease (AD) and mild cognitive impairment (MCI) has been evaluated using tests of past public knowledge, such as famous personalities and events, and tests of autobiographical memory. Reports of temporal gradients (TG) in retrograde amnesia have been inconclusive. Here, we compared the remembrance of famous historic events by patients with amnesic MCI and early AD using the newly developed Historic Events Test (HET). The HET demands knowledge about famous public events of the past 60 years divided into five time segments, and consists of three tasks, Recognition, Dating Accuracy, and Contextual Memory. In both patient groups, the performance was worse than in healthy controls. Memory performance of all time segments was uniformly affected by this kind of retrograde amnesia. There was no evidence of a TG, and memory decline was similar in all three tasks of the HET. In contrast, for the same patients tested at the same time, we had previously found a TG for autobiographical memory with better preservation of remote than recent memories (Leyhe, Müller, Milian, Eschweiler, & Saur, 2009). We propose that recall of more frequently retrieved remote autobiographical facts and incidents has become independent of the hippocampus, whereas more seldomly retrieved recent autobiographical memory and knowledge of famous events remain dependent on the hippocampus and will thereby be susceptible to the early neurodegenerative damage of the hippocampus in AD. Our assumption may reconcile the Cortical Reallocation Theory and the Multiple Trace Theory.

Confabulation denotes the emergence of memories of experiences and events which never took place. Whether there are distinct forms with distinct mechanisms is still debated. In this study, we explored 4 forms of confabulation and their mechanisms in 29 amnesic patients. Patients performed tests of explicit memory, executive functions, and two test of orbitofrontal reality filtering (memory selection and extinction capacity in a reversal learning task) previously shown to be strongly associated with confabulations that patients act upon and disorientation. Results indicated the following associations: (1) Intrusions in a verbal memory test (simple provoked confabulations) dissociated from all other forms of confabulation and were not associated with any specific cognitive measure. (2) Momentary confabulations, defined as confabulatory responses to questions and measured with a confabulation questionnaire, were associated with impaired mental flexibility, a tendency to fill gaps in memory, and with one measure of reality filtering. Momentary confabulations, therefore, may emanate from diverse causes. (3) Behaviourally spontaneous confabulation, characterized by confabulations that the patients act upon and disorientation, was strongly associated with failure in the two reality filtering tasks. Behaviourally spontaneous confabulation may be seen as a specific instance of momentary confabulations with a distinct mechanism. (4) A patient producing fantastic confabulations with nonsensical, illogical content had wide-spread cognitive dysfunction and failed in the reality filtering tasks. The results support the presence of truly or partially dissociable types of confabulation with different mechanisms.

Autobiographical memory includes the retrieval of personal semantic data and the remembrance of incident or episodic memories. In retrograde amnesias, it has been observed that recall of autobiographical memories of recent events is poorer than recall of remote memories. Alzheimer's disease (AD) may also be associated with a temporal gradient (TG) in memory decline, though studies have yielded inconsistent results on this point. They have also yielded inconsistent results on whether AD might differentially affect semantic and episodic remembrance. Here, we compared autobiographical memory of childhood, early adulthood, and recent life among healthy control (HC) subjects, patients with early AD, and patients with amnesic mild cognitive impairment (aMCI). Both the aMCI and AD patients exhibited declines in recall of autobiographical incidents and semantic information. In AD patients, both components of autobiographical memory had a clear TG, with better preservation of memories of childhood than those of early adulthood and recent life. The TG of autobiographical memory decline in AD patients is more compatible with the Cortical Reallocation Theory than with the Multiple Trace Theory of memory consolidation. In contrast to AD patients, aMCI patients exhibited impaired recall of personal facts and autobiographical incidents relating only to recent life. The significant decline in autobiographical memory for recent life that occurred in aMCI patients suggests that deterioration of consolidation of personal facts and events begins with commencement of functional impairment in the hippocampus.

The fact that pictures are better remembered than words has been reported in the literature for over 30 years. While this picture superiority effect has been consistently found in healthy young and older adults, no study has directly evaluated the presence of the effect in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). Clinical observations have indicated that pictures enhance memory in these patients, suggesting that the picture superiority effect may be intact. However, several studies have reported visual processing impairments in AD and MCI patients which might diminish the picture superiority effect. Using a recognition memory paradigm, we tested memory for pictures versus words in these patients. The results showed that the picture superiority effect is intact, and that these patients showed a similar benefit to healthy controls from studying pictures compared to words. The findings are discussed in terms of visual processing and possible clinical importance.

Our objective was to study the neural correlates of naming of newly learned unfamiliar objects in subjects with mild cognitive impairment (MCI) and in age-matched controls, by using positron emission tomography (PET). Prior to the PET scanning, each subject underwent a 4-day long training period in which 40 names of rare unfamiliar objects were taught. The stimuli consisted of five categories: unfamiliar objects for which both the name and the definition (=semantic support) were given during training, unfamiliar objects with only the name given, unfamiliar objects with no information given, familiar objects and visual noise patterns. The unfamiliar objects mainly represented ancient domestic tools unknown to modern-day people. When naming newly learned objects trained without semantic support, the MCI group showed increased activation in the anterior cingulate when compared with the controls. Our results suggest that the naming of newly learned objects posed additional executive and attentional demands on the patients.

Recent research has revealed a recognition bias favoring positive faces and other stimuli in older compared to younger adults. However, it is yet unclear whether this bias reflects an age-related preference for positive emotional stimuli, or an affirmatory bias used to compensate for episodic memory deficits. To follow up this point, the present study examined recognition of emotional faces and current mood state in patients with mild Alzheimer disease (AD) and healthy controls. Expecting lower overall memory performance, more negative and less positive mood in AD patients, the critical question was whether the positivity-related recognition bias would be increased compared to cognitively unimpaired controls. Eighteen AD patients and 18 healthy controls studied happy, neutral, and angry faces, which in a subsequent recognition task were intermixed with 50% distracter faces. As expected, the patient group showed reduced memory performance, along with a less positive and more negative mood. The recognition bias for positive faces persisted. This pattern supports the view that the positivity-induced recognition bias represents a compensatory, gist-based memory process that is applied when item-based recognition fails.