Prospective memory performance of patients with Parkinson's disease depends on shifting aptitude: evidence from cognitive rehabilitation.

This study investigated the effect of cognitive training aimed at improving shifting ability on Parkinson's disease (PD) patients' performance of prospective memory (PM) tasks. Using a double-blind protocol, 17 PD patients were randomly assigned to two experimental arms. In the first arm (n=9) shifting training was administered, and in the second (placebo) arm (n=8), language and respiratory exercises. Both treatments consisted of 12 sessions executed over 4 weeks. PM and shifting measures (i.e., Trail Making Test and Alternate Fluency Test) were administered at T0 (before treatment) and T1 (immediately after treatment). A mixed analysis of variance was applied to the data. To evaluate the effects of treatment, the key effect was the interaction between Group (experimental vs. placebo) and Time of Assessment (T0 vs. T1). This interaction was significant for the accuracy indices of the PM procedure (p<.05) and for the performance parameters of the shifting tasks (p ≤.05). Tukey's HSD tests showed that in all cases passing from T0 to T1 performance significantly improved in the experimental group (in all cases p ≤.02) but remained unchanged in the placebo group (all p consistently>.10). The performance change passing from T0 to T1 on the Alternate Fluency test and the PM procedure was significantly correlated (p<.05). Results show that the cognitive training significantly improved PD patients' event-based PM performance and suggest that their poor PM functioning might be related to reduced shifting abilities.

Standardization and normative data obtained in the Italian population for a new verbal fluency instrument, the phonemic/semantic alternate fluency test.

The phonemic/semantic alternate fluency test seems to overcome some limits of the instruments currently used to assess set-shifting abilities. In particular, this test does not make high demands on motor systems because the subject is required to rapidly change mental set to generate words by continuously alternating between phonemic and semantic criteria. Thus, it is potentially feasible for use in individuals who have movement disorders. In this regard, some data support its sensitivity in revealing cognitive impairments in people suffering from frontal-striatal-related disorders. The first aim of this study was to provide standardization and normative data for the phonemic/semantic alternate fluency test. The second aim was to upgrade normative data for the single phonemic and semantic fluency tests. For these purposes, we administered to a sample of 335 healthy Italian subjects (ranging from 20 to 90 years), a test consisting of the following three subtests: (1) a single letter-cued (phonemic) fluency subtest; (2) a single category-cued (semantic) subtest; (3) a phonemic/semantic alternate fluency subtest. A composite shifting index was also derived to capture the shifting cost a subject pays passing from performance of the two single fluency subtests to performance of the alternate fluency subtest. We computed correction grids to adjust raw scores for age, literacy and gender according to the results of regression analyses. Moreover, we computed equivalent scores to permit direct and fast comparison of performance on the three fluency tests.

Mini mental Parkinson test: standardization and normative data on an Italian sample.

The mini mental Parkinson (MMP) is a test built to overcome the limits of the mini mental state examination (MMSE) in the short-time screening of cognitive disorders in individuals with Parkinson's disease (PD). In fact, in this scale, items tapping executive functioning are included to better capture PD-related cognitive changes. Some data sustain the sensitivity and validity of the MMP in the short neuropsychological screening of these individuals. Here, we report normative data on the MMP we collected on a sample of 307 Italian healthy subjects ranging from 40 to 91 years. The results document a detrimental effect of age and an ameliorative effect of education on the MMP total performance score. We provide for correction grids for age and literacy that derive from results of the regression analyses. Moreover, we also computed equivalent scores in order to allow a direct and fast comparison between the performance on the MMP and on other psychometric measures that can be administered to the subjects.

The effectiveness of an immersive virtual reality and telemedicine-based cognitive intervention on prospective memory in Parkinson's disease patients with mild cognitive impairment and healthy aged individuals: design and preliminary baseline results of a placebo-controlled study.

Introduction: Prospective memory (PM) impairments have been extensively documented in individuals with Parkinson's disease associated with mild cognitive impairment (PD-MCI) and in those with healthy aging. Considering how PM failure decreases individuals' quality of life and functional independence in the activities of daily living, training to enhance this ability could be a prior target of intervention. Objective: Here, we aimed to present the study protocol and preliminary results of a novel immersive virtual reality (IVR) and telemedicine-based (TM) cognitive intervention focused on executive abilities (i.e., planning, shifting, and updating) to improve PM functioning in PD-MCI patients and healthy elderly individuals. Methods: Outcome measures, collected before, immediately after and 2 months after the intervention, included: (1) pre-post training changes in objective cognitive functioning, evaluated with tests assessing executive functions and PM; (2) pre-post training changes in subjective perception of memory functioning, psychiatric symptoms, autonomy in daily living and quality of life, evaluated using the appropriate scales; (3) usability, feasibility and users' compliance with the proposed IVR and telemedicine program. The efficacy of this intervention compared to an active control condition is currently being evaluated in a randomized, double-blind controlled trial, which will be conducted on 30 eligible PD-MCI patients and 30 older adults. Results: Preliminary results concerning between-group comparisons of demographic and neuropsychological screening data show a good balance among the intervention groups considered in this study. The results also suggest good levels of usability, feasibility and acceptability, thus supporting the notion that our intervention can be used to promote cognitive functioning, even in people with cognitive decline. Conclusion: Considering the relatively low costs and easy accessibility to this program, it could prove valuable in primary prevention initiatives and early cognitive rehabilitation for dementia risk reduction.

The dopaminergic system supports flexible and rewarding dyadic motor interactive behaviour in Parkinson's Disease.

Studies indicate that the dopaminergic system (DAS) supports individual flexible behaviour. While flexibility is quintessential to effective dyadic motor interactions, whether DAS mediates adaptations of one's own motor behaviour to that of a partner is not known. Here, we asked patients with Parkinson's Disease (PD) to synchronize their grasping movements with those of a virtual partner in conditions that did (Interactive) or did not (Cued) require to predict and adapt to its actions. PD performed the task during daily antiparkinsonian treatment ('On' condition) or after drug-withdrawal ('Off' condition). A group of healthy individuals also served as control group. In the Interactive condition, PDs performed better and found the interaction more enjoyable when in 'On' than in 'Off' condition. Crucially, PD performance in the 'On' condition did not differ from that of healthy controls. This pattern of results hints at the key role of the DAS in supporting the flexible adaptation of one's own actions to the partner's during motor interactions.

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.

Implicit prototype learning in patients with memory deficit: Evidence from a study with Alzheimer's disease patients.

OBJECTIVE: In a previous study (Zannino et al., 2012), it was demonstrated that individuals with amnestic mild cognitive impairment (MCI) were unimpaired on a new prototype learning task consisting of morphed faces (face prototype learning task [FPLT]). This paradigm was devised to improve on the classical dot pattern task by ruling out any reliance on residual episodic memory or working memory resources. In the present study, we aimed to demonstrate: first, that people with even more severe episodic memory impairment than MCI are unimpaired on a fully implicit prototype learning task and second, that the dot pattern task, at variance with the FPLT, requires a no negligible contribution from the episodic memory system. METHOD: Twenty-four persons with Alzheimer's disease (AD) and 48 healthy controls took part in this experiment. As in the original study, in addition to the FPLT, they were also administered the classical dot pattern task and an ordinary forced-choice face recognition task. RESULTS: AD performed like normal controls in the FPLT but scored significantly worse on the dot pattern task and the face recognition task. Interestingly, although performance on the face recognition task did not correlate with that on the FPLT, a significant correlation was observed between the face recognition and the dot pattern task. CONCLUSIONS: Results support both of our claims: first, that also severe amnesic people can learn new visual prototypes with a fully implicit paradigm and, second, that the classical dot pattern task requires some degree of episodic resources. Further research is needed to rule out the role of working memory in solving the FPLT. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cognitive and mental health changes and their vulnerability factors related to COVID-19 lockdown in Italy.

The COVID-19 pandemic and government imposed social restrictions like lockdown exposed most individuals to an unprecedented stress, increasing mental health disorders worldwide. We explored subjective cognitive functioning and mental health changes and their possible interplay related to COVID-19-lockdown. We also investigated potential risk factors to identify more vulnerable groups. Across Italy, 1215 respondents completed our Qualtrics-based online-survey during the end of a seven to 10-week imposed lockdown and home confinement (from April 29 to May 17, 2020). We found subjective cognitive functioning and mental health severely changed in association with the lockdown. Under government regulations, cognitive complaints were mostly perceived in routine tasks involving attention, temporal orientation and executive functions-with no changes in language abilities. A paradoxical effect was observed for memory, with reduced forgetfulness compared to pre-lockdown. We found higher severity and prevalence of depression, anxiety disorders, abnormal sleep, appetite changes, reduced libido and health anxiety: with mild-to-severe depression and anxiety prevalence climbing to 32 and 36 percent, respectively, under restrictions. Being female, under 45 years, working from home or being underemployed were all identified as relevant risk factors for worsening cognition and mental health. Frequent consumers of COVID-19 mass media information or residents in highly infected communities reported higher depression and anxiety symptoms, particularly hypochondria in the latter. If similar restrictions are reimposed, governments must carefully consider these more vulnerable groups in their decisions, whilst developing effective global and long-term responses to the cognitive and mental health challenges of this type of pandemic; as well as implementing appropriate psychological interventions with specific guidelines: particularly regarding exposure to COVID-19 mass-media reports.

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.

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.

A pilot study on the effect of cognitive training on BDNF serum levels in individuals with Parkinson's disease.

Parkinson's disease (PD) patients, besides motor dysfunctions, may also display mild cognitive deficits (MCI) which increase with disease progression. The neurotrophin brain-derived neurotrophic factor (BDNF) plays a role in the survival of dopaminergic neurons and in the regulation of synaptic connectivity. Moreover, the brain and peripheral level of this protein may be significantly reduced in PD patients. These data suggest that a cognitive rehabilitation protocol aimed at restoring cognitive deficits in PD patients may also involve changes in this neurotrophin. Thus, in this pilot study we evaluated the effect of a cognitive rehabilitation protocol focused on the training of executive functioning and measured BDNF serum levels in a group of PD patients with mild cognitive impairment, as compared to the effect of a placebo treatment (n = 7/8 group). The results showed that PD patients undergoing the cognitive rehabilitation, besides improving their cognitive performance as measured with the Zoo Map Test, also displayed increased serum BDNF levels as compared to the placebo group. These findings suggest that BDNF serum levels may represent a biomarker of the effects of cognitive rehabilitation in PD patients affected by MCI. However, the functional significance of this increase in PD as well as other neuropathological conditions remains to be determined.

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.

Free and cued recall memory in Parkinson's disease associated with amnestic mild cognitive impairment.

The hypothesis has been advanced that memory disorders in individuals with Parkinson's disease (PD) are related to either retrieval or consolidation failure. However, the characteristics of the memory impairments of PD patients with amnestic mild cognitive impairment have not been clarified. This study was aimed at investigating whether memory deficits in PD patients with amnestic mild cognitive impairment (PDaMCI) are due to failure of retrieval or consolidation processes. Sixteen individuals with PDaMCI, 20 with amnestic mild cognitive impairment without PD (aMCINPD), and 20 healthy controls were recruited. Participants were administered the Free and Cued Selective Reminding Test. An index of cueing was computed for each subject to capture the advantage in retrieval of cued compared to free recall. Individuals with PDaMCI performed worse than healthy controls on the free recall (p<0.01) but not the cued recall (p>0.10) task, and they performed better than aMCINPD subjects on both recall measures (p<0.01). The index of cueing of subjects with PD was comparable to that of healthy controls (p>0.10) but it was significantly higher than that of the aMCINPD sample (p<0.01). Moreover, PD patients' performance on free recall trials was significantly predicted by scores on a test investigating executive functions (i.e., the Modified Card Sorting Test; p = 0.042). Findings of the study document that, in subjects with amnestic mild cognitive impairment associated to PD, episodic memory impairment is related to retrieval rather than to consolidation failure. The same data suggest that, in these individuals, memory deficits might be due to altered frontal-related executive functioning.

Performing prototype distortion tasks requires no contribution from the explicit memory systems: evidence from amnesic MCI patients in a new experimental paradigm.

Evidence shows that amnesic patients are able to categorize new exemplars drawn from the same prototype as in previously encountered items. It is still unclear, however, whether this ability is due to a spared implicit learning system or residual explicit memory and/or working memory resources. In this study, we used a new paradigm devised expressly to rule out any possible contribution of episodic and working memory in performing a prototype distortion task. We enrolled patients with amnesic MCI and Normal Controls. Our paradigm consisted of a study phase and a test phase; two-thirds of the participants performed the study phase and all participants performed the test phase. In the study phase, participants had to judge how pleasant morphed faces, drawn from a single prototype, seemed to them. Half of the participants were shown faces drawn from the A-prototype and half from the B-prototype. A- and B-faces were opposite in a morphing space with a neutral human face at the center. In the test phase, participants had to judge the regularity of faces they had never seen before. Three different types of faces were shown in the test phase, that is, A-, B-, or neutral-faces. We expected that implicit learning of the category boundaries would lead to a category-specific increase in perceived regularity. The results confirmed our predictions. In fact, trained subjects (compared with subjects who did not undergo the study phase) assigned higher regularity scores to new faces drawn from the same prototype as the faces seen during training, and they gave lower regularity scores to new faces drawn from the opposite prototype. This effect was super imposable across subjects' groups.

Event-based prospective memory failure in amnestic mild cognitive impairment.

Prospective memory (PM) deficits have recently been documented in individuals with amnestic mild cognitive impairment (aMCI). In this paper, we investigated whether these deficits are due to the failure of retrospective memory processes. We also examined the role played by attentional/executive processes in PM functioning. We enrolled 24 individuals with aMCI and 24 healthy controls (NCs). In the PM procedure, we manipulated both the memory load of the retrospective component of the PM task and the complexity of the ongoing task in a 2 × 2 experimental design. Sequences of four words were presented. Participants had to repeat the sequence in the same order (low attentional demand condition) or in the reverse order (high attentional demand condition). When a target word appeared in the sequence, participants had to press a button on the keyboard (PM task). Target words could be one (low memory load condition) or four (high memory load condition) in different blocks. MCI participants obtained lower PM scores than NCs in all four experimental conditions. However, they recalled the target words less accurately than NCs only in one four-word condition. Finally, the executive demand of the ongoing task did not significantly affect the PM performance of aMCI individuals. Our findings confirm that PM is severely impaired in individuals with aMCI. Moreover, a failure of retrospective memory processes does not seem to fully account for the poor PM performance in aMCI individuals. Finally, the finding that in these individuals, a deficit in executive control cannot be claimed as the main responsible for the observed PM impairment could suggest the involvement of automatic-reflexive processes.

Prospective memory functioning in mild cognitive impairment.

OBJECTIVE: The present study aimed to investigate prospective memory (PM) in persons with mild cognitive impairment (MCI). METHOD: Twenty individuals with MCI (10 with an amnestic profile and 10 with a dysexecutive profile of cognitive impairment) and 20 control subjects (CS) were recruited. In the PM tasks, subjects had to execute three actions after 20 min had elapsed (time-based condition) or after a timer rang (event-based condition). Separate scores were computed for correct recall of the intention to perform the actions (prospective component) and for correct execution of the actions (retrospective component). RESULTS: Although individuals with MCI were less accurate than CS in both prospective (Cohen's d ranged from 1.04 to 2.23) and retrospective (Cohen's d ranged from 0.81 to 1.06) components of the experimental task, they were significantly more impaired in the former than the latter component (Cohen's d = 0.42). Moreover, the deficit in the prospective component of the time-based task was particularly evident in MCI participants presenting with a dysexecutive impairment in respect to amnestic MCI individuals (Cohen's d = 0.99). CONCLUSIONS: Results of the present study show that the ability of subjects with MCI to comply effectively with a planned delayed intention is impaired and suggest that dysexecutive disorders are likely responsible for this deficit.