Rationale and protocol of the ENGAGE study: a double-blind randomized controlled preference trial using a comprehensive cohort design to measure the effect of a cognitive and leisure-based intervention in older adults with a memory complaint.

BACKGROUND: Leisure activities can be both enjoyable and cognitively stimulating, and participation in such activities has been associated with reduced age-related cognitive decline. Thus, integrating stimulating leisure activities in cognitive training programs may represent a powerful and innovative approach to promote cognition in older adults at risk of dementia. The ENGAGE study is a randomized controlled, double-blind preference trial with a comprehensive cohort design that will test the efficacy and long-term impact of an intervention that combines cognitive training and cognitively stimulating leisure activities. METHODS: One hundred and forty-four older adults with a memory complaint will be recruited in Montreal and Toronto. A particular effort will be made to reach persons with low cognitive reserve. Participants will be randomly assigned to one of two conditions: cognitive + leisure training (ENGAGE-MUSIC/SPANISH) or active control (ENGAGE-DISCOVERY). The ENGAGE-MUSIC/SPANISH training will include teaching of mnemonic and attentional control strategies, casual videogames selected to train attention, and classes in music or Spanish as a second language. The ENGAGE-DISCOVERY condition will comprise psychoeducation on cognition and the brain, low-stimulating casual videogames and documentary viewing with discussions. To retain the leisure aspect of the activities, participants will be allowed to exclude either music or Spanish at study entry if they strongly dislike one of these activities. Participants randomized to ENGAGE-MUSIC/SPANISH who did not exclude any activity will be assigned to music or Spanish based on a second random assignment. Training will be provided in 24 2-h sessions over 4 months. Outcomes will be measured at baseline, at 4-month follow-up, and at 24-month follow-up. The primary outcome will be cognitive performance on a composite measure of episodic memory (delayed recall scores for words and face-name associations) measured at baseline and at the 4-month follow-up. Secondary outcomes will include a composite measure of attention (speed of processing, inhibition, dual tasking, and shifting), psychological health, activities of daily living, and brain structure and function and long-term maintenance measured at the 24-month follow-up. Information on cognitive reserve proxies (education and lifestyle questionnaires), sex and genotype (apolipoprotein (Apo)E4, brain-derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT)) will be collected and considered as moderators of training efficacy. DISCUSSION: This study will test whether a program combining cognitive training with stimulating leisure activities can increase cognition and reduce cognitive decline in persons at risk of dementia. TRIAL REGISTRATION: NCT03271190 . Registered on 5 September 2017.

The effect of divided attention on memory for items and their context.

Memory for context, in comparison to memory for items, is a more demanding task and requires more attentional resources. We examined differences between item and context memory using divided attention at encoding and retrieval. Participants were presented with word lists and were instructed to learn the items (i.e., words), the intrinsic context (i.e., the colour of the cards on which each word was presented), and the extrinsic context (i.e., the temporal order of the words). Among 72 young adults, in comparison to conditions of full attention, divided attention applied at encoding only or retrieval only resulted in equally lower performance on all memory tasks; in contrast, divided attention applied at both encoding and retrieval resulted in lower performance only on memory for temporal order. The findings support the idea that memory for temporal order requires greater attentional resources and strategic processing than memory for items.

Normative data for clustering and switching on verbal fluency tasks.

Normative data for clustering and switching on verbal fluency tasks are provided. Four hundred and eleven healthy adults between the ages of 18 and 91 were given tests of phonemic fluency (FAS or CFL) and semantic fluency (Animals and Supermarket). Raw scores were corrected for demographic (i.e., age, education, and sex) and test (i.e., fluency form) variables that were determined to make sizable contributions to fluency performance. These normative data should be useful for clinicians and researchers in determining the nature of the fluency impairment in any given individual.

Component analysis of verbal fluency in patients with schizophrenia.

OBJECTIVE: Clustering and-switching components of phonemic fluency performance were compared in patients with schizophrenia and healthy normal controls. BACKGROUND: These components were selected to provide evidence for a specific anatomic locus for the breakdown of language processes or for a multiple-disease model of schizophrenia. METHOD: As part of a larger battery of neuropsychological tests, phonemic fluency tests were administered on an individual basis. On separate 60-second trials, participants were instructed to generate words beginning with the letters C, F, and L, excluding proper names and variants of the same word. Three scores were obtained for each participant: (1) number of words generated, excluding errors and repetitions; (2) mean cluster size; and (3) raw number of switches. RESULTS: The patients showed small but significant impairments in clustering and larger impairments in switching relative to normal controls. CONCLUSIONS: This pattern suggests a relatively greater deficit in functioning in the frontal lobe than in the temporal lobe. However, neither measure was able to completely discriminate patients with schizophrenia from controls. Moreover, differences in fluency performance were observed among subtypes of schizophrenia. Taken together, the findings of impaired performance for both aspects of fluency, differences between subtypes, and the failure to completely discriminate patients with schizophrenia from controls indicate that there is not a single marker of the disease, at least among these fluency variables. Instead, the current findings are more supportive of a multiple-disease model of schizophrenia.

Source memory and divided attention: reciprocal costs to primary and secondary tasks.

Source memory, in comparison with item memory, is more sensitive to frontal lesions and may require more strategic processing. Divided attention was used to restrict attentional resources and strategic processing on memory tasks. Participants encoded and retrieved items (i.e., words) and source (i.e., voice or spatial location) while concurrently performing a finger-tapping (FT) or visual reaction-time (VRT) task. Memory accuracy costs under divided attention were greater for retrieval of source than item and were greater with VRT than FT. Similarly, costs to the secondary task were greater when concurrently retrieving source as opposed to item and were greater for VRT than FT. Effects were stronger when spatial location was used as the source task. Findings support the idea that processing source information requires more attentional resources and effort than processing item information. Furthermore, concurrent performance of VRT produced greater interference with a task that was more dependent on intact frontal functioning and better simulated the performance of patients with frontal dysfunction.

Longitudinal analysis of phonemic clustering and switching during word-list generation in Huntington's disease.

Two characteristics of word-list generation performance are forming clusters (i.e., contiguous words from the same subcategory) and switching among them. Patients with frontal lobe pathology show reduced switching on letter-cued word generation tasks, and clustering has been associated with temporal lobe functioning. Letter-cued word generation was examined in 72 patients with Huntington's disease (HD) and 41 healthy participants of equivalent age and education. As predicted, the patients showed reduced switching but normal clustering. In addition, switching but not clustering correlated inversely with disease severity, as measured by both movement and mental status scales. Furthermore, 5-year longitudinal analysis revealed a monotonic decrease in switching over time, whereas clustering performance remained stable. Control participants performed uniformly over time on both measures. These results are consistent with a progressive reduction in cognitive flexibility attributed to disruption of frontal-subcortical circuits secondary to neostriatal pathology in HD.

Clustering and switching on verbal fluency: the effects of focal frontal- and temporal-lobe lesions.

We examined the hypothesis that, on verbal fluency, clustering (i.e. generating words within subcategories) is related to temporal-lobe functioning, whereas switching (i.e. shifting between subcategories) is related to frontal-lobe functioning. Tests of phonemic and semantic fluency were administered to 53 patients with focal frontal-lobe lesions (FL), 23 patients with unilateral temporal-lobe lesions (TL) and 55 matched controls. Performance by FL patients was consistent with our hypothesis: in comparison to controls, patients with left-dorsolateral or superior-medial frontal lesions switched less frequently and produced normal cluster sizes on both phonemic and semantic fluency. Performance by TL patients was not consistent across fluency tasks and provided partial support for our hypothesis. On phonemic fluency, TL patients were unimpaired on both switching and clustering. On semantic fluency, TL patients were impaired on switching in comparison to controls and left TL patients produced smaller clusters than right TL patients. The best indices for discriminating the patient groups, therefore, were phonemic-fluency switching (impaired only with frontal lesions) and semantic-fluency clustering (impaired only with temporal-lobe lesions).

Clustering and switching on verbal fluency tests in Alzheimer's and Parkinson's disease.

Two components of verbal fluency performance--clustering (i.e., generating words within subcategories) and switching (i.e., shifting between subcategories)--were examined in patients with dementia of the Alzheimer type (DAT), patients with dementia with Parkinson's disease (DPD), nondemented patients with Parkinson's disease (NPD), and demographically matched controls. The DAT and DPD groups were impaired in the number of words generated on both phonemic and semantic fluency. The DAT group produced smaller clusters on both tasks and switched less often on semantic fluency than controls. The DPD group switched less often on both tasks and produced smaller clusters on phonemic fluency than controls. The NPD group was not impaired on any fluency variable. Thus, the total number of words generated on phonemic and semantic fluency did not discriminate the dementia groups from their respective control groups, but measures of clustering and switching did. This differential pattern of performance provides evidence for the potential usefulness of measures of switching and clustering in the assessment of dementia.

Chronic obstructive pulmonary disease: effects of hypoxia on neurological and neuropsychological measures.

Eighteen patients with chronic obstructive pulmonary disease (COPD) were administered a series of pulmonary, neurological, and neuropsychological measures to test if there was an effect of COPD on neurological and cognitive functioning. Overall, there was no evidence of general dementia in this sample. Measures of immediate and delayed memory, complex attention, and speed of information processing correlated highly with arterial carbon dioxide partial pressure and, to a lesser extent, with oxygen partial pressure. Measures of language abilities, perceptual-motor functioning, and simple attention generally were not related to arterial gas pressures. A similar pattern of findings was obtained when group differences were examined between participants classified as severely hypoxic or mildly hypoxic, although group differences were mitigated by premorbid IQ differences. Hypoxia in COPD results in a relatively focused pattern of impairment in measures of memory function and tasks requiring attention allocation. The memory dysfunction may be related to involvement of limbic memory regions necessary for explicit memory. The attentional deficits were attributed to diffuse brain involvement resulting in reduced resource allocation. Early diagnosis and treatment of the hypoxia is essential.

Clustering and switching as two components of verbal fluency: evidence from younger and older healthy adults.

Although verbal fluency is a frequently used neuropsychological test, little is known about the underlying cognitive processes. The authors proposed that 2 important components of fluency performance are clustering (i.e., the production of words within semantic or phonemic subcategories) and switching (i.e., the ability to shift between clusters). In Experiment 1, correlational data from 54 older and 41 younger adults indicated that both components were highly correlated with the number of words generated on semantic fluency, whereas switching was more highly correlated than clustering with the number of words generated on phonemic fluency. On semantic fluency, younger participants generated more words and switched more frequently than older participants; on phonemic fluency, older participants produced larger clusters than younger participants. In Experiment 2, among 22 young adults, divided attention decreased the number of words generated and decreased switching on phonemic fluency only. Overall, findings suggest that clustering and switching are dissociable fluency components and that switching is related to frontal-lobe functioning.

Conceptual reasoning as a mediator of verbal recall in patients with multiple sclerosis.

A number of intercorrelated factors, including level of neurologic impairment, age, and conceptual reasoning, appear to be related to memory performance among patients with Multiple Sclerosis (MS). A battery of neuropsychological tests was administered to 131 patients with MS ranging in age from 19 to 76 years, with a mean symptom duration of 12.3 years and an overall mild level of MS-related neurologic impairment. Regression analyses indicated that neurologic impairment and age each contributed uniquely to the prediction of delayed free recall of a word list. Furthermore, when the effect of conceptual reasoning was accounted for, neither neurologic impairment nor age were significantly related to recall. Thus, a mediated relation was confirmed, supporting the idea that a significant portion of neurologic-impairment-related and age-related differences in recall are due to differences in conceptual reasoning that are important for optimal performance on tests of recall. Additional analyses failed to support a similar mediated relation using recognition rather than recall as the measure of memory performance.