Impact of Combined Resistance and Cognitive Training on BDNF and Cognitive Function in Older Adults

Study Identification and Background Information

• Study Title: Resistance Training Combined With Cognitive Training Increases Brain Derived Neurotrophic Factor and Improves Cognitive Function in Healthy Older Adults.

• Publication Details: Published in Frontiers in Psychology on 14 October 2022. DOI: $10.3389/fpsyg.2022.870561$.

• Lead Authors: Luz Albany Arcila Casta%%o, Vivian Castillo de Lima, Marco Carlos Uchida, et al.

• Institutional Affiliations: Applied Kinesiology Laboratory (University of Campinas, Brazil), National Center for Geriatrics and Gerontology (Japan), and NIH Biomedical Research Center (University of Maryland, US).

• Aging Context: Aging involves progressive organic deterioration and decline in physiological functions, contributing to geriatric syndromes and chronic diseases. The World Health Organization (WHO) emphasizes focus on age-related decreases in neuromuscular performance and cognitive functioning as vital to healthy aging and functional independence.

• Scientific Context of Sarcopenia/Frailty: Aging negatively impacts neuromuscular function, reducing mobility, muscle mass, strength, and power. Muscle atrophy and decreased physical performance are core diagnostic criteria for frailty and sarcopenia. These conditions are major risk factors for adverse events, including falls.

• Cognitive Function Definitions: Cognition represents mental processes facilitating interaction between the body and environment. Memory, attention, and executive functions are progressively affected by age, impairing Instrumental Activities of Daily Living (IADL).

• Verbal Abilities: Includes the capacity to retrieve grammatical representations and word sounds, typically assessed via Verbal Fluency (VF) tasks.

• Dual-Task Paradigm: Daily activities often require simultaneous motor and cognitive tasks (dual tasks). Aging impairs the ability to perform these (e.g., walking and talking together), which is viewed as a poor health prognosis.

• BDNF (Brain-Derived Neurotrophic Factor): A protein involved in neurogenesis, synaptic plasticity, neuronal morphology, and neuropathology. While theoretical bases suggest exercise induces BDNF improvements, existing research on Resistance Training (RT) alone has shown limited or inconsistent effects on BDNF levels.

Experimental Methods and Materials

• Study Design: A two-arm parallel randomized trial comparing Traditional Resistance Training (TRT) and Resistance Training combined with Cognitive Training (RT+CT).

• Participants: A convenience sample of $57$ older adults was initially recruited; $30$ were randomized ($15$ per group). Eligibility included age $\ge 60$ years, community-dwelling status, and sufficient physical/cognitive abilities.

• Exclusion Criteria: Participation in physical activity programs within $3$ months prior, skeletal muscle disorders, cardiovascular/pulmonary/neurological/psychiatric diseases, Mini-Mental State Examination (MMSE) score < 24, or absence in more than $10$ of sessions.

• Final Sample Characteristics:

  • RT+CT ($n=13$): Age $66.3 \pm 4.6$ years, $31$ men, formal education $16.3 \pm 2.0$ years.

  • TRT ($n=12$): Age $70.0 \pm 8.1$ years, $25$ men, formal education $14.8 \pm 4.0$ years.

• Intervention Duration: $16$ weeks total, consisting of a $2$-week familiarization period (no cognitive tasks) and a $14$-week training period.

• Session Structure: Sessions lasted $\sim 60$ minutes (5-min warm-up, 50-min exercise, 5-min cool-down), performed twice weekly in groups of four supervised by two trainers.

• Exercise Regiment: Eight exercises utilizing Nakagym equipment, free weights, and body weight. The order was: leg press, dumbbell lateral raise, lateral pulldown, abdominal crunch, back extension, seated leg curl, bench press, and standing calf raise.

• Intensity and Volume Progression:

  • Weeks 3%%10: $2$ sets of $8$ submaximal reps at $60$ of $1$-repetition maximum ($1RM$).

  • Weeks 11%%13: $3$ sets of $8$ submaximal reps at $60$ of $1RM$.

  • Weeks 14%%15: $3$ sets of $8$ submaximal reps at $70$ of $1RM$.

  • Auxiliary Exercises: (Lateral raise, crunch, back extension, calf raise) at $3$ sets of $12$ repetitions based on Rating of Perceived Exertion (RPE CR-10 scale).

• Load Adjustment: If RPE was below target, loads increased $2$ for upper extremity and $5$ for lower extremity exercises.

• Cognitive Task (RT+CT Group): Executed Verbal Fluency (VF) simultaneously with RT exercise sets. Difficulty increased monthly from general categories (e.g., colors, countries) to specific categories. Phonological categories (words starting with specific letters) were also used.

Assessment Methodologies

• Physical Function Tests:

  • Isometric Handgrip Strength (IHG): Measured with Saehan hydraulic dynamometer (SH5001) in a sitting position. Relative IHG was calculated as $IHG / BMI$.

  • 10-m Walk Test (10MWT): Evaluated walking speed at usual and fast pace over a $12$ course (with $1$ for acceleration and $1$ for deceleration).

  • Five-Times Sit-to-Stand (5XSTS): Time taken to rise from an $87$ chair five times as fast as possible.

  • Timed Up-and-Go (TUG): Time to rise, walk $3$, turn, return, and sit.

  • One-Leg Stand: Maximum balance time (up to $30$) with knee flexed at 90^%%circ.

• Cognitive Function Tests:

  • Semantic Verbal Fluency (SVF): Number of animals named in $1$.

  • Phonological Verbal Fluency (PVF): Number of words beginning with "A" named in $1$.

  • Dual-Task TUG (TUG-cog): TUG performed while naming animals.

  • Scenery Picture Memory Test (SPMT): Analyzing an image with $23$ objects for $1$ and recalling them after a $1$ interval.

  • Trail-Making Test (TMT): Part A (sequential numbers $1$) and Part B (alternating numbers and letters $1$).

• Biometrics and Plasma BDNF:

  • Body Composition: Measured via Tanita BC-108 electrical bioimpedance ($50$) using eight electrodes.

  • BDNF Assay: Plasma collected after $48$ abstention from exercise, measured via ELISA (Sigma-Aldrich, Ref: RAB0026).

Results: Physical Performance and Body Composition

• Physical Gains: Both TRT and RT+CT showed similar significantly improved scores ($p = 0.001$) for:

  • Absolute and Relative IHG ($\sim 25$ improvement).

  • Fast Walking Speed ($11.7$ for RT+CT; $18.7$ for TRT).

  • 5XSTS ($\sim 24$ reduction in time).

  • TUG ($\sim 15$ reduction in time).

  • $1RM$ Leg Press ($\sim 53$ increase).

  • $1RM$ Lateral Pulldown and Leg Curl (significant increases across both groups).

• Body Composition: No significant changes were observed in body weight, BMI, Lean Body Mass (LBM), Appendicular Skeletal Muscle Mass (ASMM), or Fat Mass in either group after $16$ weeks.

• Total Training Volume: Increased significantly ($p = 0.001$) by $\sim 145$ in both groups, confirming the progression of the training stimulus.

Results: Cognitive Function and BDNF Levels

• Verbal Fluency: Only the RT+CT group showed significant improvements in Semantic Verbal Fluency ($28$ increase; p < 0.001) and Phonological Verbal Fluency ($31.5$ increase; $p = 0.09$ for time, but post-hoc identified RT+CT improvement specifically).

• Memory (SPMT): Improved only in the RT+CT group ($p = 0.03$).

• Dual-Task Performance (TUG-cog): Significant improvements observed in both groups ($18.4$ RT+CT; $15.1$ TRT).

• Plasma BDNF Concentration:

  • A significant group $\times$ time interaction ($p = 0.001$) was found.

  • RT+CT Group: Increased from $757 \pm 260$ to $1,158 \pm 483 \text{ pg/mL}$.

  • TRT Group: Experienced a non-significant decrease from $1,001 \pm 367$ to $780 \pm 320 \text{ pg/mL}$.

• Correlations: Positive significant correlations were found between post-training BDNF levels and SVF scores ($r = 0.463; p = 0.039$) as well as PVF scores ($r = 0.461; p = 0.040$).

Discussion and Mechanistic Theories

• Physical Function Findings: The study confirms that RT (with or without CT) effectively counteracts age-related neuromuscular deterioration. Improvements in IHG and TUG have direct implications for reducing risks of frailty and sarcopenia.

• Cognitive Contrast: The lack of cognitive improvement in the TRT group aligns with some previous studies (Tsutsumi et al., 1997), while contrasting with others (Cassilhas et al., 2007) that utilized longer durations (e.g., $6$ months) or different intensities. The results suggest $16$ weeks is sufficient for combined training but perhaps not for RT alone to elicit cognitive change.

• Transfer of Training Theory:

  • Near-transfer Effect: Adaptations are specific to the stimuli (e.g., verbal fluency tasks improving verbal fluency test performance). This was observed in RT+CT.

  • Far-transfer Effect: Stimuli for training are distinct from transfer tasks. The study found limited evidence for far transfer (e.g., no significant change in attention/TMT scores).

• Guided Plasticity Facilitation Framework: This conceptual model explains the synergistic benefits of simultaneous physical and cognitive tasks.

  • Facilitation Effect: Physical exercise increases neural growth factors like BDNF.

  • Guidance Effect: Cognitive exercises guide the formation of new synapses and neural activation.

• Conclusion: Combined RT and Cognitive Training (RT+CT) is a superior strategy for healthy older adults to simultaneously enhance physical strength, cognitive verbal fluency, and plasma BDNF levels. TRT is effective for physical scores but does not influence BDNF or verbal cognitive domains within this study duration.