Crosswords may help keep Alzheimer’s at bay

In a 78-week study, computerized games and crossword puzzles had no differential impact on within-network DMN* functional connectivity (FC) in individuals with mild cognitive impairment (MCI) who are at high risk of developing Alzheimer’s disease (AD). However, crosswords appear to have a slight advantage over the other in other aspects.

The DMN is a resting-state functional network of various highly interconnected cortical hubs, including the anteromedial frontal, inferolateral parietal, and posteromedial parietal cortices, which has been implicated in the progression of MCI to AD. [Neurology 2011;76;511-517]

“Our hypothesis was that computerized cognitive games training (CCT) would normalize changes in the DMN from MCI, compared with a crossword puzzle control condition, and that the resulting network changes would correlate with a slowing of cognitive decline or with cognitive improvement,” said the researchers.

“[However, we found] no treatment-related differences between crosswords and games in the primary outcome measure of within-network DMN FC (p<0.05),” they said. “[The] maximal effects of crosswords on the DMN and related networks [may have occurred] at the end of the more intensive phase of training and dissipated over the 18-month duration of the trial, given that subjects were only scanned at entry and exit.”

The researchers randomized 107 participants (mean age 71.2 years, 58 percent female) to either CCT or crossword puzzles. Resting-state functional MRI (fMRI) was obtained at baseline and 18 months to evaluate differences in fMRI measured within- and between-network DMN FC and other large-scale brain networks: the executive control, salience, and sensorimotor networks (ECN, SLN, and SMN, respectively). [J Alzheimers Dis 2023;91:483-494]

Crosswords may have the upper hand

On subgroup analysis however, a statistically significant difference was found between CCT and crosswords in DMN within-network connectivity among those with late MCI (p=0.034). In this subgroup, within-network DMN FC over the course of the trial dropped with CCT but increased with crossword (–0.039 vs 0.027).

This finding could translate to a benefit for crosswords in this patient subset, which has a higher degree of functional and cognitive impairment and faster progression rate than those with early MCI. [Alzheimers Dement 2010;6:239-246]

Furthermore, week 78 saw reductions in between-network FC in the DMN and all other networks with CCT (–0.012, –0.061, and –0.043 for ECN, SLN, and SMN, respectively) as opposed to crosswords (–0.001, 0.036, and 0.001, respectively). However, statistical significance was only seen between the DMN and SLN (p=0.04).

The greater fraction of ApoE** 4 carriers in the CCT vs the crossword arm (54 percent vs 38 percent) could have biased the former group toward faster decline, the researchers said.

Also, the level of compliance could have been higher with crosswords owing to its familiarity. “[C]rossword puzzles are considered a cognitive leisure activity and decreased perceived stress levels of the activity may increase compliance,” they explained.

Crossword puzzles require the use of multiple cognitive abilities (ie, attention, executive function, language skills, processing speed, retrieval memory, verbal knowledge) which, when used simultaneously, may have durable cognitive benefits. [J Int Neuropsychol Soc 2011;17:1006-1013]

“Crossword puzzles … might non-specifically engage multiple specialized cognitive networks at a low level, nevertheless synergistically, resulting in cognitively beneficial remodelling of the DMN that, in subjects with late MCI, exceeds that of more domain-specific types of training characteristic of CCT,” they added.

Nonetheless, these findings are exploratory and should thus be validated further, they continued.