Does Cue Focality Modulate Age-related Performance in Prospective Memory? An fMRI Investigation.

How prospective memory (PM) weakens with increasing age has been largely debated. We hypothesized that automatic and strategic PM processes, respectively mediated by focal and non-focal cues, are differently affected by aging, even starting from 50-60 years of age. We investigated this issue using a 2 × 2 design in which focal and non-focal experimental conditions were created by varying the conjoint nature of the ongoing task (lexical decision vs. syllable matching tasks) and the PM cue (words vs. syllables). In the whole-brain analysis we found that the left inferior frontal gyrus and the middle cingulate cortex were more activated when young compared to older individuals performed a PM task; moreover, the anterior cingulate cortex was selectively activated during non-focal PM when the cues were words. In a region-of-interest analysis we observed that the medial and the lateral portions of the rostral prefrontal cortex were associated with the focal and non-focal conditions respectively, more in young than in older adults. Our findings provide evidence in support of early age-related differences in automatic/strategic PM functioning.

Protecting cognition from aging and Alzheimer's disease: a computerized cognitive training combined with reminiscence therapy.

OBJECTIVE: The aim of this paper was to assess the efficacy of process-based cognitive training (pb-CT) combined with reminiscence therapy (RT) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and in healthy elderly (HE) subjects. METHODS: This multicenter, randomized, controlled trial involved 348 participants with mAD, MCI, and HE from four European countries. Participants were randomly assigned to two arms of a crossover design: those in arm A underwent 3 months of computerized pb-CT for memory and executive functions combined with RT and 3 months of rest; those in arm B underwent the reverse. The primary outcome was the effect of the training on memory and executive functions performance. The secondary outcome was the effect of the training on functional abilities in mAD assessed with the instrumental activities of daily living. RESULTS: We found a significant effect of the training for memory in all three groups on delayed recall of the Rey Auditory Verbal Learning Test and for executive functions in HE on the phonological fluency test. MCI and HE participants maintained these effects at follow-up. MCI and mAD participants also showed a significant effect of the training on the Mini-mental state examination scale. Participants with mAD showed more stable instrumental activities of daily living during the training versus the rest period. CONCLUSIONS: Our results corroborate the positive effect of pb-CT and its maintenance primarily on memory in HE and MCI participants that did not seem to be potentiated by RT. Moreover, our results are very promising for the mAD participants.

Interception of vertically approaching objects: temporal recruitment of the internal model of gravity and contribution of optical information.

Introduction: Recent views posit that precise control of the interceptive timing can be achieved by combining on-line processing of visual information with predictions based on prior experience. Indeed, for interception of free-falling objects under gravity's effects, experimental evidence shows that time-to-contact predictions can be derived from an internal gravity representation in the vestibular cortex. However, whether the internal gravity model is fully engaged at the target motion outset or reinforced by visual motion processing at later stages of motion is not yet clear. Moreover, there is no conclusive evidence about the relative contribution of internalized gravity and optical information in determining the time-to-contact estimates. Methods: We sought to gain insight on this issue by asking 32 participants to intercept free falling objects approaching directly from above in virtual reality. Object motion had durations comprised between 800 and 1100 ms and it could be either congruent with gravity (1 g accelerated motion) or not (constant velocity or -1 g decelerated motion). We analyzed accuracy and precision of the interceptive responses, and fitted them to Bayesian regression models, which included predictors related to the recruitment of a priori gravity information at different times during the target motion, as well as based on available optical information. Results: Consistent with the use of internalized gravity information, interception accuracy and precision were significantly higher with 1 g motion. Moreover, Bayesian regression indicated that interceptive responses were predicted very closely by assuming engagement of the gravity prior 450 ms after the motion onset, and that adding a predictor related to on-line processing of optical information improved only slightly the model predictive power. Discussion: Thus, engagement of a priori gravity information depended critically on the processing of the first 450 ms of visual motion information, exerting a predominant influence on the interceptive timing, compared to continuously available optical information. Finally, these results may support a parallel processing scheme for the control of interceptive timing.

Subjective organization in the episodic memory of individuals with Parkinson's disease associated with mild cognitive impairment.

Word clustering (i.e., the ability to reproduce the same word pairs in consecutive recall trials of an unrelated word list) has been extensively investigated as a proxy of subjective organization (SO) of memorandum. In healthy subjects and in groups of brain-damaged patients, the rate of SO generally predicts accuracy of word list recall. This study aimed at evaluating SO in the performance of patients with Parkinson's disease (PD) on a word list recall task in order to investigate the basic mechanisms of episodic memory impairment that are frequently observed in these patients. For this purpose, 56 PD patients, who were stratified according to the presence and quality of mild cognitive impairment (MCI), and a group of healthy controls (HCs) were administered a word list task and an extensive battery of neuropsychological tests. Results showed that recall accuracy on the word list task progressively decreased passing from HC to PD patients without cognitive impairment, to patients with single-domain dysexecutive MCI and to patients with multiple-domain dysexecutive and amnesic MCI. Conversely, only the latter PD group showed a lower SO score than that achieved by the other groups. In the overall PD group, correlational and regression analyses demonstrated that SO scores and a composite score of executive functions were not reciprocally related, but both provided an independent and significant contribution to the prediction of word list recall accuracy. These data are discussed in terms of the contribution of executive functions and hippocampal storage processes to the onset of memory impairment in PD.

Medio-lateral functional dissociation of the rostral prefrontal cortex with focal/non-focal cues during a prospective memory task.

The rostral prefrontal cortex (rPFC) is crucial in prospective memory (PM) behavior. Several functional magnetic resonance imaging studies showed that its medial (mrPFC) and lateral (lrPFC) portions dissociate during PM tasks. In light of the Multiprocess theory (McDaniel and Einstein 2000), here we tested whether the two portions of the rPFC are dissociable by modulating strategic vs. spontaneous processes during a PM task. We investigated these two processes by means of a 2 × 2 experimental design in which focal vs. non-focal conditions were modulated by varying the conjoint nature of the ongoing task (i.e., lexical decision vs. syllable matching) and the PM cue (words vs. syllables). Using the two portions of the rPFC as regions of interest, we found an effect of the non-focal condition in the lrPFC and, conversely, an effect of the focal condition in the mrPFC. In the whole-brain analysis we found an effect of the non-focal condition in the bilateral intraparietal sulcus, the bilateral middle frontal gyrus, the supplementary motor areas and the vermis of the cerebellum, whereas we found an effect of the focal condition in the ventromedial PFC. Overall, our results show that different brain regions are involved when multiple processes underlying PM behavior are modulated.

Apathy in individuals with Parkinson's disease associated with mild cognitive impairment. A neuropsychological investigation.

Apathy is frequently reported in individuals with Parkinson's disease (PD) and is hypothesized to be associated with frontal-striatal related cognitive functions. Available data, however, do not provide univocal results. Moreover, this relationship has been poorly investigated in PD patients with mild cognitive impairment (MCI). This study was aimed at investigating the association between severity of apathy of PD patients and their performance on neuropsychological tests investigating executive abilities. Individuals with PD (i.e., with and without MCI) and healthy controls (HCs) were administered a neuropsychological test battery that investigated episodic memory, language, short-term memory and attention, visual-spatial abilities and executive functions. Subjects were also administered additional neuropsychological tests to evaluate the different executive subcomponents (i.e., planning/abstract reasoning, self-monitoring/response inhibition, working memory, shifting and fluency). The Apathy Evaluation Scale (AES) was administered to assess apathy severity. Linear regression analyses were applied to the data; results showed that in the PD group with MCI, the best cognitive factor associated to the AES score was patients' scores on the executive tests and, in particular, their scores on tests examining planning/abstract reasoning. By contrast, in the PD group without MCI, the cognitive performance was not significantly associated to apathy severity. Findings of the study document a specific association between reduced efficiency of the executive system and apathy severity in individuals with PD and MCI. This association indirectly supports the hypothesis of a relationship between motivational disorders and dysregulation of the activity of the frontal-striatal networks in PD patients.

The contribution of different prefrontal cortex regions to recollection and familiarity: a review of fMRI data.

Dual-process theories of recognition memory sustain that recollection and familiarity reflect different mnemonic processes and rely on separate neural substrates that are located primarily in the medial temporal lobe (MTL). Aggleton and Brown's model (1999) assumes that this distinction extends to other brain regions, including the thalamus, and that both recognition memory processes interact with the prefrontal cortex (PFC). Nevertheless, it is still unclear whether recollection and familiarity are subtended by separate prefrontal regions. Here we provided a review of the literature that first focused on functional magnetic resonance imaging studies that adopted the Remember/Know method and reported recollection- and familiarity-based activity in the PFC. There is evidence that functional activations are differently located within the lateral (i.e., along the dorso-ventral axis), medial (i.e., along the rostro-caudal axis) and anterior (i.e., along the medio-lateral axis) prefrontal surfaces according to whether they are recollection- or familiarity-related. Overall, the findings we summarise suggest that recollection and familiarity are qualitatively different processes and rely on distinct neural pathways even outside the MTL.

Brain-derived neurotrophic factor serum levels correlate with cognitive performance in Parkinson's disease patients with mild cognitive impairment.

Brain-derived neurotrophic factor (BDNF) is a trophic factor regulating cell survival and synaptic plasticity. Recent findings indicate that BDNF could be a potential regulatory factor for cognitive functioning in normal and/or neuropathological conditions. With regard to neurological disorders, recent data suggest that individuals with Parkinson's disease (PD) may be affected by cognitive deficits and that they have altered BDNF production. Therefore, the hypothesis can be advanced that BDNF levels are associated with the cognitive state of these patients. With this in mind, the present study was aimed at exploring the relationship between BDNF serum levels and cognitive functioning in PD patients with mild cognitive impairment (MCI). Thirteen PD patients with MCI were included in the study. They were administered an extensive neuropsychological test battery that investigated executive, episodic memory, attention, visual-spatial and language domains. A single score was obtained for each cognitive domain by averaging z-scores on tests belonging to that specific domain. BDNF serum levels were measured by enzyme-linked immunoassay (ELISA). Pearson's correlation analyses were performed between BDNF serum levels and cognitive performance. Results showed a significant positive correlation between BDNF serum levels and both attention (p < 0.05) and executive (p < 0.05) domains. Moreover, in the executive domain we found a significant correlation between BDNF levels and scores on tests assessing working memory and self-monitoring/inhibition. These preliminary data suggest that BDNF serum levels are associated with cognitive state in PD patients with MCI. Given the role of BDNF in regulating synaptic plasticity, the present findings give further support to the hypothesis that this trophic factor may be a potential biomarker for evaluating cognitive changes in PD and other neurological syndromes associated with cognitive decline.

Time-based prospective memory functioning in mild cognitive impairment associated with Parkinson's disease: relationship with autonomous management of daily living commitments.

OBJECTIVE: Prospective memory (PM), that is, the ability to keep in memory and carry out intentions in the future, is reported to be impaired in individuals with Parkinson's disease (PD). PM failure may be also associated with reduced daily living functioning in these patients. Little is known, however, about the relationship between mild cognitive impairment (MCI) and time-based PM functioning in PD patients and the possible impact of PM deficits on patients' autonomy in daily living. Here we aimed to investigate whether MCI associated with PD affects time-based PM. We also wished to determine whether PM impairment accounts for reduced autonomous management of medication in these patients. METHOD: The study included 48 PD patients with MCI, 33 PD patients without cognitive disorders (PDN) and 20 healthy controls. The time-based PM procedure required that subjects perform an action after a fixed time. The PM procedure was incorporated in the standard neuropsychological assessment. One score was computed for the ability to retrieve the intention (prospective component) and one for remembering the action to be executed (retrospective component). The Pill Questionnaire was administered to assess the ability to manage medication. RESULTS: PD patients with MCI performed less accurately in the PM procedure than HC and tended to perform poorer than PDN. Moreover, in PD patients with MCI, accuracy on the prospective component of the PM task and performance on the Modified Card Sorting Test significantly predicted the ability to manage medication. CONCLUSIONS: RESULTS document that reduced efficiency of time-based PM processes in PD is specifically related to the presence of MCI. The same data indicate that PM weakness may be associated with impaired daily living functioning and decreased autonomy.

Prospective memory performance in individuals with Parkinson's disease who have mild cognitive impairment.

OBJECTIVE: Prospective memory (PM) is the ability to keep in memory and realize future intentions. We aimed at investigating whether in Parkinson's disease (PD) PM deficits are related to mild cognitive impairment (MCI). Other aims were to investigate the cognitive abilities underlying PM performance, and the association between PM performance and measures of daily living functioning. METHOD: The study included 15 PD patients with single domain MCI, 15 with multiple domain MCI, 17 PD patients without cognitive disorders (PDNC) and 25 healthy controls (HCs). All subjects were administered a PM procedure that included focal (PM cue is processed in the ongoing task) and nonfocal (PM cue is not processed in the ongoing task) conditions. PD patients were administered an extensive neuropsychological battery and scales to assess daily living abilities. RESULTS: PD patients with MCI (both single and multiple domains) showed lower accuracy on all PM conditions than both HC and PDNC patients. This was predicted by their scores on shifting indices. Conversely, PM accuracy of PDNC patients was comparable to HCs. Regression analyses revealed that PD patients' PM performance significantly predicted scores on daily living scales Conclusions: Results suggest that PM efficiency is not tout-court reduced in PD patients, but it specifically depends on the presence of MCI. Moreover, decreased executive functioning, but not episodic memory failure, accounts for a significant proportion of variance in PM performance. Finally, PM accuracy indices were found to be associated with measures of global daily living functioning and management of medication.