Preventing dementia? Interventional approaches in mild cognitive impairment

Breton A., Casey D., Arnaoutoglou N.A.

Mild cognitive impairment (MCI) is regarded as a prodrome to dementia. Various cognitive tests can help with diagnosis; meta-analysis of diagnostic accuracy studies would assist clinicians in choosing optimal tests.We searched online databases for "mild cognitive impairment" and "diagnosis" or "screening" from 01/01/1999 to 01/07/2017. Articles assessing the diagnostic accuracy of a cognitive test compared with standard diagnostic criteria were extracted. Risk of bias was assessed. Bivariate random-effects meta-analysis was used to evaluate sensitivity and specificity.Eight cognitive tests (ACE-R, CERAD, CDT-Sunderland, IQCODE, Memory Alteration Test, MMSE, MoCA, and Qmci) were considered for meta-analysis. ACE-R, CERAD, MoCA, and Qmci were found to have similar diagnostic accuracy, while the MMSE had lower sensitivity. Memory Alteration Test had the highest sensitivity and equivalent specificity to the other tests.Multiple cognitive tests have comparable diagnostic accuracy. The Memory Alteration Test is short and has the highest sensitivity. New cognitive tests for MCI diagnosis should not be compared with the MMSE.

Mahendran R., Gandhi M., Moorakonda R.B., Wong J., Kanchi M.M., Fam J., Rawtaer I., Kumar A.P., Feng L., Kua E.H.

Mild cognitive impairment (MCI) is a phase in cognitive decline when it is still possible to intervene to reverse the decline. Cognitive stimulation delivered through psychosocial interventions provides both psychological intervention and social stimulation to improve cognition. A pilot open-label parallel-arms randomized controlled trial was undertaken to examine the effects of art therapy (AT) and music reminiscence activity (MRA) compared to the control, on the primary outcome of neurocognitive domain assessments in elderly people with MCI. Community-living elderly people with MCI (Petersen’s criteria), assessed for study eligibility, were randomized using a web-based system with equal allocation to two intervention arms: AT (guided viewing of art pieces and production of visual arts) and MRA (listening, and recalling memories related to music) and a control arm (standard care without any intervention). Interventions were led by trained therapists weekly for 3 months, then fortnightly for 6 months. Neurocognitive domains (mean of memory, attention, and visuo-spatial abilities standardized scores), psychological wellbeing (subsyndromal depression and anxiety) and telomere length as a biological marker of cellular ageing, were assessed by intervention-blinded assessors at baseline, 3 months and 9 months. In total, 250 people were screened and 68 were randomized and included in the analysis. In the AT arm, neurocognitive domains improved compared to the control arm at 3 months (mean difference (d) = 0.40; 90% CI 0.126, 0.679) and were sustained at 9 months (d = 0.31; 90% CI 0.068, 0.548). There was some improvement in depression and anxiety at 3 and 9 months and in telomere length at 9 months, but this was not significant. Similar improvements were observed in the MRA arm over the control arm, but they were not significant. There were no intervention-related adverse effects. Art therapy delivered by trained staff as “art as therapy” and “art psychotherapy” may have been the significant contributor to cognitive improvements. The findings support cognitive stimulation for elderly people with cognitive decline and signal the need for larger studies and further investigation of carefully designed psycho-social interventions for this group. Clinical Trials.gov, NCT02854085 . Registered on 7 July 2016.

Zhu Y., Wu H., Qi M., Wang S., Zhang Q., Zhou L., Wang S., Wang W., Wu T., Xiao M., Yang S., Chen H., Zhang L., Zhang K., Ma J., et. al.

Mild cognitive impairment (MCI) is known as a transitional stage or phase between normal aging and dementia. In addition, it is associated with an increased risk of dementia. Research has shown that moderate-intensity exercise is associated with a decreased risk of cognitive impairment. Two recent studies demonstrated that dance interventions are associated with improved cognitive function in the elderly with MCI.We evaluated the effect of a moderate-intensity aerobic dance routine on the cognitive function in patients with MCI.This is a single-blind randomized controlled trial. Sixty MCI patients were randomized to receive either treatment (aerobic dance routine + usual care) or control (usual care only) for 3 months. All patients received usual care for an additional 3 months thereafter. The aerobic dance routine was a specially designed dance routine which involved cognitive effort for patients to memorize the complex movements. Wechsler memory scale-revised logical memory (WMS-R LM) and event-related evoked potentials (ERPs) P300 latency were used to assess patients' cognitive function at baseline, 3 months, and 6 months.Twenty-nine patients received exercise therapy and 31 patients received usual care. Patients in the treatment group showed a greater improvement in memory (difference in WMS-R LM changes over 3 months 4.6; 95% CI 2.2, 7.0; p

Zhao J., Li H., Lin R., Wei Y., Yang A.

Elderly people with mild cognitive impairment (MCI) are at high risk for dementia. This study compared the effects of standard cognitive training with a creative expression (CrExp) program.Adult patients with MCI aged 60 years and older (N=93) were randomly assigned to either CrExp therapy (n=48) or a control group who received standard cognitive training (n=45) for 16 weeks. The Montreal Cognitive Assessment, Chinese Version of the Auditory Verbal Learning Test, Chinese Version of the Category Verbal Fluency Test, Digit Span Test, Trail Making Test, Chinese Version of Activities of Daily Living scale, and Memory Satisfaction Questionnaire were used to measure cognitive functioning and daily living abilities. Assessments were administered at baseline, postintervention, and 6 months follow-up.At postintervention, patients receiving CrExp therapy scored significantly higher than patients receiving standard cognitive training, in general cognitive functioning, memory, executive function, functional status, and everyday living ability. The improvements in cognitive functioning were maintained at the 6 month follow-up.CrExp therapy has greater positive effects on cognitive functions and daily living ability than standard cognitive training. This unique therapy may serve as a cost-effective adjunct to standard interventions for older adults with mild cognitive impairment.

Choi W., Lee S.

Sungkarat S., Boripuntakul S., Kumfu S., Lord S.R., Chattipakorn N.

Background. Effects of Tai Chi (TC) on specific cognitive function and mechanisms by which TC may improve cognition in older adults with amnestic mild cognitive impairment (a-MCI) remain unknown. Objective. To examine the effects of TC on cognitive functions and plasma biomarkers (brain-derived neurotrophic factor [BDNF], tumor necrosis factor-α [TNF-α], and interleukin-10 [IL-10]) in a-MCI. Methods. A total of 66 older adults with a-MCI (mean age = 67.9 years) were randomized to either a TC (n = 33) or a control group (n = 33). Participants in the TC group learned TC with a certified instructor and then practiced at home for 50 min/session, 3 times/wk for 6 months. The control group received educational material that covered information related to cognition. The primary outcome was cognitive performance, including Logical Memory (LM) delayed recall, Block Design, Digit Span, and Trail Making Test B minus A (TMT B-A). The secondary outcomes were plasma biomarkers, including BDNF, TNF-α, and IL-10. Results. At the end of the trial, performance on the LM and TMT B-A was significantly better in the TC group compared with the control group after adjusting for age, gender, and education ( P < .05). Plasma BDNF level was significantly increased for the TC group, whereas the other outcome measures were similar between the 2 groups after adjusting for age and gender ( P < .05). Conclusions. TC training significantly improved memory and the mental switching component of executive function in older adults with a-MCI, possibly via an upregulation of BDNF.

Petersen R.C., Lopez O., Armstrong M.J., Getchius T.S., Ganguli M., Gloss D., Gronseth G.S., Marson D., Pringsheim T., Day G.S., Sager M., Stevens J., Rae-Grant A.

ObjectiveTo update the 2001 American Academy of Neurology (AAN) guideline on mild cognitive impairment (MCI).MethodsThe guideline panel systematically reviewed MCI prevalence, prognosis, and treatment articles according to AAN evidence classification criteria, and based recommendations on evidence and modified Delphi consensus.ResultsMCI prevalence was 6.7% for ages 60–64, 8.4% for 65–69, 10.1% for 70–74, 14.8% for 75–79, and 25.2% for 80–84. Cumulative dementia incidence was 14.9% in individuals with MCI older than age 65 years followed for 2 years. No high-quality evidence exists to support pharmacologic treatments for MCI. In patients with MCI, exercise training (6 months) is likely to improve cognitive measures and cognitive training may improve cognitive measures.Major recommendationsClinicians should assess for MCI with validated tools in appropriate scenarios (Level B). Clinicians should evaluate patients with MCI for modifiable risk factors, assess for functional impairment, and assess for and treat behavioral/neuropsychiatric symptoms (Level B). Clinicians should monitor cognitive status of patients with MCI over time (Level B). Cognitively impairing medications should be discontinued where possible and behavioral symptoms treated (Level B). Clinicians may choose not to offer cholinesterase inhibitors (Level B); if offering, they must first discuss lack of evidence (Level A). Clinicians should recommend regular exercise (Level B). Clinicians may recommend cognitive training (Level C). Clinicians should discuss diagnosis, prognosis, long-term planning, and the lack of effective medicine options (Level B), and may discuss biomarker research with patients with MCI and families (Level C).

Young D.K., NG P.Y., Kwok T., Cheng D.

Persons with mild cognitive impairment (PwMCI) are at a higher risk of developing dementia than those without cognitive impairment. This research study aims to evaluate the effectiveness of a holistic health group intervention, which is based on the holistic brain health approach as well as an Eastern approach to health care, on improving the cognitive ability of Chinese PwMCI.In a randomized controlled trial (RCT), 38 Chinese PwMCI were randomly assigned to either a 10-session holistic health intervention group or the control group. The holistic health treatment group attempted to promote the acceptance of their illness, enhance memory and coping skills, develop a positive lifestyle, maintain positive emotions, and facilitate emotional support among participants. The 10-session holistic health group intervention was structured, with each session conducted once per week and ~90 minutes in length. Control group patients and their family caregivers received standardized basic educational materials that provided basic information on cognitive decline for them to read at home. The Montreal Cognitive Assessment (MoCA) test was used to assess the cognitive ability of PwMCI in the pre- and posttreatment periods by a research assistant who was blind to the group assignment of the participants.The paired-samples t-test indicated that the treatment group (n=18) showed significant improvement in the MoCA score, whereas the control group (n=20) did not. Moreover, 2×2 (group × time) repeated-measures analysis of covariance (ANCOVA) demonstrated that the holistic health group treatment was significantly more effective than the control intervention in improving the MoCA score, with a moderate effect size, and improving the delayed recall (ie, short-term memory), with a strong effect size, after controlling for age, sex, education, and marital status.This present RCT provides evidence to support the feasibility and effectiveness of the holistic health group intervention in improving the cognitive and short-term memory abilities of PwMCI.

Bahar-Fuchs A., Webb S., Bartsch L., Clare L., Rebok G., Cherbuin N., Anstey K.J.

Computerized Cognitive Training (CCT) has been shown to improve cognitive function in older adults with mild cognitive impairment (MCI) or mood-related neuropsychiatric symptoms (MrNPS), but many questions remain unresolved.To evaluate the extent to which CCT benefits older adults with both MCI and MrNPS, and its effects on meta-cognitive and non-cognitive outcomes, as well as establish whether adapting difficulty levels and tailoring to individuals' profile is superior to generic training.Older adults with MCI (n = 9), MrNPS (n = 11), or both (MCI+, n = 25) were randomized into a home-based individually-tailored and adaptive CCT (n = 21) or an active control condition (AC; n = 23) in a double-blind design. Interventions lasted 8-12 weeks and outcomes were assessed after the intervention, and at a 3-month follow-up.Participants in both conditions reported greater satisfaction with their everyday memory following intervention and at follow-up. However, participants in the CCT condition showed greater improvement on composite measures of memory, learning, and global cognition at follow-up. Participants with MrNPS in the CCT condition were also found to have improved mood at 3-month follow-up and reported using fewer memory strategies at the post-intervention and follow-up assessments. There was no evidence that participants with MCI+ were disadvantaged relative to the other diagnostic conditions. Finally, informant-rated caregiver burden declined at follow-up assessment in the CCT condition relative to the AC condition.Home-based CCT with adaptive difficulty and personal tailoring appears superior to more generic CCT in relation to both cognitive and non-cognitive outcomes. Mechanisms of treatment effect and future directions are discussed.

Lazarou I., Parastatidis T., Tsolaki A., Gkioka M., Karakostas A., Douka S., Tsolaki M.

Background: Many studies have highlighted the positive effects of dance in people with neurodegenerative diseases. Objectives: To explore the effects of International Ballroom Dancing on cognitive function in elders with amnestic mild cognitive impairment (aMCI). Methods: One-hundred twenty-nine elderly patients with aMCI diagnosis (mean age 66.8 ± 10.1 years) were randomly assigned into 2 groups: intervention group (IG, n = 66) and control group (CG, n = 63). The IG exercised systematically for 10 months, and both groups were submitted to extensive neuropsychological assessment prior and after the 10-month period. Results: According to the independent sample t test at the follow-up, significant differences between groups were found in benefit of the IG while the CG showed worse performance in the majority of neuropsychological tests. According to the Student t test, better performance is detected in IG in contrast with CG, which had worse performance almost in all scales. Conclusion: Dance may be an important nonpharmacological approach that can benefit cognitive functions.

Doi T., Verghese J., Makizako H., Tsutsumimoto K., Hotta R., Nakakubo S., Suzuki T., Shimada H.

To test the hypothesis that a long-term, structured cognitive leisure activity program is more effective than a health education program at reducing the risk of further cognitive decline in older adults with mild cognitive impairment syndrome (MCI), a high risk for dementia.A 3-arm, single-blind randomized controlled trial.Community.A total of 201 Japanese adults with MCI (mean age: 76.0 years, 52% women).Participants were randomized into 1 of 2 cognitive leisure activity programs (60 minutes weekly for 40 weeks): dance (n = 67) and playing musical instruments (n = 67), or a health education control group (n = 67).Primary outcomes were memory function changes at 40 weeks. Secondary outcomes included changes in Mini-Mental State Examination and nonmemory domain (Trail Making Tests A and B) scores.At 40 weeks, the dance group showed improved memory recall scores compared with controls [mean change (SD): dance group 0.73 (1.9) vs controls 0.01 (1.9); P = .011], whereas the music group did not show an improvement compared with controls (P = .123). Both dance [mean change (SD): 0.29 (2.6); P = .026] and music groups [mean change (SD): 0.46 (2.1); P = .008] showed improved Mini-Mental State Examination scores compared with controls [mean change (SD): -0.36 (2.3)]. No difference in the nonmemory cognitive tests was observed.Long-term cognitive leisure activity programs involving dance or playing musical instruments resulted in improvements in memory and general cognitive function compared with a health education program in older adults with MCI.UMIN-CTR UMIN000014261.

Wang H., Trocmé-Thibierge C., Stucky A., Shah S.M., Kvasic J., Khan A., Morain P., Guignot I., Bouguen E., Deschet K., Pueyo M., Mocaer E., Ousset P., Vellas B., Kiyasova V.

The apolipoprotein E ε4 (APOE4) genotype is a prominent late-onset Alzheimer’s disease (AD) risk factor. ApoE4 disrupts memory function in rodents and may contribute to both plaque and tangle formation. Coimmunoprecipitation and Western blot detection were used to determine: 1) the effects of select fragments from the apoE low-density lipoprotein (LDL) binding domain and recombinant apoE subtypes on amyloid beta (Aβ)42-α7 nicotinic acetylcholine receptor (α7nAChR) interaction and tau phosphorylation in rodent brain synaptosomes; and 2) the level of Aβ42-α7nAChR complexes in matched controls and patients with mild cognitive impairment (MCI) and dementia due to AD with known APOE genotypes. In an ex vivo study using rodent synaptosomes, apoE141–148 of the apoE promotes Aβ42-α7nAChR association and Aβ42-induced α7nAChR-dependent tau phosphorylation. In a single-blind study, we examined lymphocytes isolated from control subjects, patients with MCI and dementia due to AD with known APOE genotypes, sampled at two time points (1 year apart). APOE ε4 genotype was closely correlated with heightened Aβ42-α7nAChR complex levels and with blunted exogenous Aβ42 effects in lymphocytes derived from AD and MCI due to AD cases. Similarly, plasma from APOE ε4 carriers enhanced the Aβ42-induced Aβ42-α7nAChR association in rat cortical synaptosomes. The progression of cognitive decline in APOE ε4 carriers correlated with higher levels of Aβ42-α7nAChR complexes in lymphocytes and greater enhancement by their plasma of Aβ42-induced Aβ42-α7nAChR association in rat cortical synaptosomes. Our data suggest that increased lymphocyte Aβ42-α7nAChR-like complexes may indicate the presence of AD pathology especially in APOE ε4 carriers. We show that apoE, especially apoE4, promotes Aβ42-α7nAChR interaction and Aβ42-induced α7nAChR-dependent tau phosphorylation via its apoE141–148 domain. These apoE-mediated effects may contribute to the APOE ε4-driven neurodysfunction and AD pathologies.

Hong S., Kim J., Jun T.

To investigate the effects of a 12-week resistance exercise program with an elastic band on electroencephalogram (EEG) patterns and cognitive function in elderly patients with mild cognitive impairment (MCI).Randomized controlled trial.Community center.Twenty-two subjects with MCI and 25 healthy volunteer subjects were randomly assigned to 1 of 4 groups: subjects with MCI who undertook the exercise program (MCI-EX; n = 10), an MCI control group (MCI-Con; n = 12), a healthy volunteer exercise group (NG-EX; n = 12), and a healthy volunteer control group (NG-Con; n = 13).The exercise group engaged in a 15-repetition maximum (15RM; 65% of 1RM) resistance exercise program for 12 weeks.Electroencephalograms, neuropsychological tests, and Senior Fitness Test.The 12-week 15RM (65% of 1RM) resistance exercise program significantly improved variables related to the physical fitness of the elderly subjects. Furthermore, for the EEG test, the MCI and NG groups showed significant differences at baseline in relative beta waves on electrodes Fp1 (P < 0.05) and F3 (P < 0.05), as well as in relative beta2 waves on F3 (P < 0.05). In addition, after the 12-week exercise intervention, differences in a region that benefits from exercise were observed between (1) the MCI-EX group in the relative theta power on F3 (P < 0.05) and the relative alpha power on T3 (P < 0.05) and in (2) the NG-EX group in the relative theta power on P3 (P < 0.05) and P4 (P < 0.01). In addition, only the score of the digit span backward in the MCI-EX group changed significantly (P < 0.05).The 12-week resistance exercise with an elastic band had a positive effect on EEG patterns in elderly subjects with MCI, along with providing physical benefits and slight changes in cognitive function in MCI-EX group.A 15RM resistance exercise program can be an effective treatment for delaying cognitive decline and improving physical fitness.

Park J., Park J.

Objective: The purpose of this study was to investigate differences between non-specific computer training (NCT) and cognition-specific computer training (CCT). Design: Randomized controlled experimental study. Setting: Local community welfare center. Subjects: A total of 78 subjects with mild cognitive impairment (MCI) were randomly assigned to the NCT ( n = 39) or CCT group ( n = 39). Intervention: The NCT group underwent NCT using Nintendo Wii for improving functional performance, while the CCT group underwent CCT using CoTras for improving function of the cognitive domain specifically. Subjects in both groups received 30-minute intervention three times a week for 10 weeks. Main measures: To identify effects on cognitive function, the Wechsler Adult Intelligence Scale (WAIS) digit span subtests, Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test–Part B (TMT-B), Rey–Osterrieth Complex Figure Test, and Modified Taylor Complex Figure (MTCF) were used. Health-related quality of life (HRQoL) was assessed using the Short-Form 36-item questionnaire. Results: After 10 weeks, the WAIS subtests (digit span forward: 0.48 ± 0.08 vs. 0.12 ± 0.04; digit span backward: 0.46 ± 0.09 vs. 0.11 ± 0.04) and HRQoL (vitality: 9.05 ± 1.17 vs. 2.69 ± 1.67; role-emotional: 8.31 ± 1.20 vs. 4.15 ± 0.71; mental health: 11.62 ± 1.63 vs. 6.95 ± 1.75; bodily pain: 4.21 ± 2.17 vs. 0.10 ± 0.38) were significantly higher in the NCT group ( P < 0.05). Conclusion: NCT was superior to CCT for improving cognitive function and HRQoL of elderly adults with MCI.

Savulich G., Piercy T., Fox C., Suckling J., Rowe J.B., O’Brien J.T., Sahakian B.J.

Huang X., Zhang S., Zhao X., Li X., Bao F., Lan Y., Zhang Y., An R., Li B., Yu F., Sun Y., Wan Q.

BackgroundEvidence on the effects of different exercise interventions on cognitive function is insufficient.AimsTo evaluate the feasibility and effects of remotely supervised aerobic exercise (AE) and resistance exercise (RE) interventions in older adults with mild cognitive impairment (MCI).MethodsThis study is a 6-month pilot three-arm randomised controlled trial. Eligible participants (n=108) were recruited and randomised to the AE group, RE group or control (CON) group with a 1:1:1 ratio. Interventions were delivered at home with remote supervision. We evaluated participants’ global cognition, memory, executive function, attention, physical activity levels, physical performance and muscle strength of limbs at baseline, 3 months (T1) and 6 months (T2) after randomisation. A linear mixed-effects model was adopted for data analyses after controlling for covariates. Tukey’s method was used for adjusting for multiple comparisons. Sensitivity analyses were performed after excluding individuals with low compliance rates.Results15 (13.89%) participants dropped out. The median compliance rates in the AE group and RE group were 67.31% and 93.27%, respectively. After adjusting for covariates, the scores of the Alzheimer’s Disease Assessment Scale-Cognitive subscale in the AE group decreased by 2.04 (95% confidence interval (CI) −3.41 to −0.67, t=−2.94, p=0.004) and 1.53 (95% CI −2.88 to −0.17, t=−2.22, p=0.028) points more than those in the CON group at T1 and T2, respectively. The effects of AE were still significant at T1 (estimate=−1.70, 95% CI −3.20 to −0.21, t=−2.69, p=0.021), but lost statistical significance at T2 after adjusting for multiple comparisons. As for executive function, the Stroop time interference in the RE group decreased by 11.76 s (95% CI −21.62 to −1.90, t=−2.81, p=0.015) more than that in the AE group at T2 after Tukey’s adjustment. No other significant effects on cognitive functions were found.ConclusionsBoth remotely supervised AE and RE programmes are feasible in older adults with MCI. AE has positive effects on global cognition, and RE improves executive function.Trial registration numberChiCTR2100045582.

Sarti P., Varrasi S., Guerrera C.S., Platania G.A., Furneri G., Torre V., Boccaccio F.M., Rivi V., Tascedda S., Pirrone C., Santagati M., Blom J.M., Castellano S., Caraci F.

Abstract Background Apathy worsens with age and cognitive decline, particularly in Alzheimer’s, leading to functional and cognitive deterioration. Comprehending its broad impact is vital for customized, preventive treatments. Methods The study examined 214 adults divided in three groups—Mild Cognitive Impairment, mild Alzheimer’s, and controls—using neuropsychological tests and questionnaires, with statistical and network analysis to explore apathy’s links with other group variables related to demographics and treatment. Results Notable differences were observed among the groups' performance of administered tests. While inferential statistics failed to return a predictive model of apathy in mild Alzheimer’s, networks and cluster analyses indicate that the demographic variables analysed have different importance at different times of disease progression and that cognitive apathy is particularly prominent in AD-related decline. Conclusions Network analysis revealed insights into dementia risk differentiation, notably the impact of sex and demographic factors, beyond the scope of traditional statistics. It highlighted cognitive apathy as a key area for personalized intervention strategies more than behavioural and emotional, emphasizing the importance of short-term goals and not taking away the person's autonomy when not strictly necessary.

Zhong T., Tian H., Wen X., Ma D., Cui H., Zhang L., Zhu X., Wang Y., Chen L.

Chiu Y., Yan S., Fan Y., Chang C., Hung R., Liu Y., Yang T.O., Chuang Y.

AbstractIntroductionAlzheimer's disease (AD) involves neuroinflammation and amyloid plaque deposition, yet the role of amyloid‐reactive immune response in neurodegeneration remains unclear. We investigate amyloid‐reactive T cell levels in the Epidemiology of Mild Cognitive Impairment Study in Taiwan (EMCIT) and Taiwan Precision Medicine Initiative of Cognitive Impairment and Dementia (TPMIC) cohorts.MethodUsing diverse amyloid peptide formulations, we established a polyfunctionality assay for five T cell functions and compared mild cognitive impairment (MCI) patients to control subjects in both cohorts.ResultsIn both cohorts, MCI individuals exhibit higher amyloid‐reactive T cell responses than controls. In the TPMIC cohort, CD4+ and CD8+ total response frequencies are notably elevated in MCI (CD4: 1.3%, CD8: 1.91%) versus controls (CD4: 0.15%, CD8: 0.28%; both p < 0.001). Amyloid‐reactive T cell response outperforms plasma phosphorylated tau 181 (p‐tau181) in discriminating MCI (area under the receiver operating characteristic curve CD4+: 0.97; CD8+: 0.96; p‐tau181: 0.72; both p < 0.001).DiscussionAmyloid‐reactive T cell polyfunctional response distinguishes MCI from normal aging and could serve as a novel MCI biomarker.Highlights Amyloid‐reactive polyfunctional T cell responses can be detected in the peripheral circulation. Amyloid‐reactive T cell response is significantly enhanced in individuals with mild cognitive impairment compared to age‐matched, cognitively unimpaired individuals. The unique discriminative accuracy of amyloid‐reactive T cell response is significantly higher than phosphorylated tau181 and is not a result of overall T cell hyperreactivity. Future studies are needed to determine the predictive role of amyloid‐reactive T cell responses in disease progression and if the amyloid‐reactive immune response could be a therapeutic target for the treatment of neurodegeneration.

Esposito F.

Chen C., Huang N., Hu B., Zhang M., Yuan J., Guo J.

Digital technology interventions (DTIs) are seen as promising interventions to prevent or delay cognitive decline in older adults, yet evidence from reviews is not conclusive. The aim of this study is to explore the effectiveness of DTIs in improving older adults’ cognitive function while taking study design and intervention characteristics as moderators. We searched the PubMed, Embase, CINAHL, PsycINFO, and Scopus databases up to May 26, 2023. Only randomized controlled trials examined the effects of DTIs on cognitive function were included in our study. Standardized mean difference (SMD) and 95% confidence interval for outcomes were applied in meta-analyses and subgroup analyses. A risk of bias assessment was also conducted. Overall, 23 eligible studies with a total sample size of 1454 participants were included. We found that DTIs significantly improved global cognitive function (SMD = 0.479), attention and processing speed (SMD = 0.488), executive function (SMD = 0.287), immediate recall (SMD = 0.266), and working memory (SMD = 0.307). Our subgroup analyses revealed that DTIs were more effective for cognitively impaired subjects, and DTIs with specific intervention characteristics, such as the inclusion of cognitive standard tasks, virtual reality-based interventions, specialized settings, professional guidance, low/medium-density training, > 24 sessions, and sessions lasting > 30 min, were more effective for different cognitive domains. This study supported the effectiveness of DTIs in improving cognitive function in older adults aged 60 years old and over, which may be influenced by study design and intervention characteristics. These findings have important implications for clinical dementia prevention and treatment strategies targeted at specific cognitive domains.

Huang M., Chen T.C., Singh F., Taaffe D., Nosaka K.

Cognitive function is improved acutely after aerobic and/or resistance exercise, but it is unclear if the types of muscle contraction can influence this effect. This study tested the hypothesis that undertaking an acute bout of exercise with eccentric than concentric contractions would be more beneficial for improving cognitive function post-exercise in older adults. Twenty healthy older adults (66–75 years) performed descending stair walking (DSW), ascending stair walking (ASW), and resistance exercise of the knee extensors with eccentric-only (RE-ECC) or concentric-only contractions (RE-CON) for ∼20 min each with a week between exercises in a randomized order. The Stroop tests of color naming (STCN) and conflicting color words (STCC), symbol digit modalities test, digit span test (DST), and two types of the trail making test (TMT-A, TMT-B) were assessed before and after sitting for 20 min (control session), and each exercise. A significant ( p < 0.05) improvement in the baseline test scores was found from the control session to the fourth exercise session. Time to complete the tests was significantly ( p < 0.05) reduced from pre- to post-exercise as well as after sitting for 20 min for STCN (−5.9 ± 7.4 s, Cohen’s d = 0.79), STCC (−8.9 ± 11.1 s, d = 0.80), TMT-A (−22.6 ± 9.7 s, d = 2.34) and TMT-B (−23.1 ± 13.7 s, d = 1.69) without significant difference among the four exercise conditions. A significant ( p < 0.05) improvement of DST score was found from pre- to post-exercise for DSW (9.0 ± 17.6%, d = 0.51) and RE-ECC (6.5 ± 10.6%, d = 0.61), but not for ASW and RE-CON. These results partially supported the hypothesis that eccentric exercise could affect acute changes in cognitive function greater than concentric exercise.

Wu T., Han T., Zhu D.

Li Y., Liu Q., Si H., Zhou W., Yu J., Bian Y., Wang C.

We aimed to identify the effect of lifespan cognitive reserve and (pre)frailty on mild cognitive impairment (MCI) among older adults. A total of 4420 older adults aged above 60 with intact cognition recruited in 2011/2012 were followed up in 2015 from the China Health and Retirement Longitudinal Study (CHARLS). The assessment of MCI was based on executive function, episodic memory, and visual-spatial ability. (Pre)frailty was assessed by the validated version of the Fried physical frailty phenotype scale. The lifespan cognitive reserve consisted of the highest educational level, occupational complexity, and participation in leisure activities. Modified Poisson regression models were used to identify the risk of MCI in relation to (pre)frailty and lifespan cognitive reserve index. We examined the interactions of (pre)frailty and lifespan cognitive reserve index on both additive and multiplicative scales. Baseline (pre)frailty significantly increased the risk of MCI after 3–4 years of follow-up, and high cognitive reserve protected individuals from the risk of MCI. There was an additive interaction between (pre)frailty and the low lifespan cognitive reserve (the relative excess interaction risk=1.08, 95 % CI= 0.25–1,91), but no multiplicative interaction (RR=0.95, 95 % CI= 0.67–1.37). The risk of MCI was larger among older adults with comorbid (pre)frailty and low cognitive reserve than those with each condition alone. Cognitive reserve attenuates the risk of MCI associated with (pre)frailty. This finding implicates the urgency for identifying and managing MCI among frail older adults who accumulate low cognitive reserve in the life course.

Aoki Morantte A.S., Medina-Rivera M.V., Nicolini H.

Mild Cognitive Impairment (MCI) is considered a decline in cognitive functions, which becomes more pronounced with age. These patients may benefit from cognitive treatments that help attenuate or slow down a potential progression towards dementia.

Peng Y., Song P., Karako T., Asakawa T.

Liu X., Cao Y.

ABSTRACTObjectivesTo investigate the intermediary role of physical performance in the association between physical activity and mild cognitive impairment (MCI) in older adults with type 2 diabetes mellitus (T2DM), residing in rural areas.MethodsThis study employed a random sampling method to select 316 patients aged 65 years and older, all diagnosed with T2DM, from 24 different rural areas in China. The relationships between physical activity, physical performance, and MCI were analyzed using a logistic regression model, and the proposed mediation model was validated through bootstrap test.ResultsIn this study, the prevalence of MCI in the rural‐based older adults with T2DM was 53.48%. A significant correlation was observed between the levels of physical activity and physical performance. Moreover, diminished physical performance was positively correlated with an increased propensity for MCI, even after adjusting for relevant covariates. Physical performance was discerned to exert a partial mediating influence on the relationship between physical activity and MCI.ConclusionsThe empirical evidence generated by this study posits that the impact of physical activity on MCI is partially mediated through physical performance in an aging population with T2DM residing in rural environments. Consequently, interventional strategies aimed at ameliorating physical performance may serve as a viable approach to mitigate the progression of cognitive decline.

Contreras-Somoza L.M., Toribio-Guzmán J.M., Irazoki E., Viñas-Rodríguez M.J., Gil-Martínez S., Castaño-Aguado M., Lucas-Cardoso E., Parra-Vidales E., Perea-Bartolomé M.V., Franco-Martín M.Á.

Objective: The aim of this study was to evaluate and compare the impressions of older adults with mild dementia/MCI (mild cognitive impairment) and people with schizophrenia towards the usability of GRADIOR (version 4.5) and their user experience (UX) with this computerized cognitive rehabilitation program. Methods: The impressions towards the usability of GRADIOR and the UX of 41 older adults with mild dementia/MCI and 41 people with schizophrenia were obtained using the User Experience Questionnaire. Results: Older adults with dementia/MCI had more positive impressions than people with schizophrenia. Both agreed that its quality was lower in Dependability. Conclusion: GRADIOR meets users’ needs and preferences but needs improvements to ensure they feel more in control when interacting with it. For people with schizophrenia, other aspects of usability and UX need improvement. Usability and UX evaluation allow the verification of technological acceptability and functionality, and to identifying specific improvements for each user group.

Papallo S., Di Nardo F., Siciliano M., Esposito S., Canale F., Cirillo G., Cirillo M., Trojsi F., Esposito F.

Background: Repetitive transcranial magnetic stimulation (rTMS) has shown therapeutic effects in neurological patients by inducing neural plasticity. In this pilot study, we analyzed the modifying effects of high-frequency (HF-)rTMS applied to the dorsolateral prefrontal cortex (DLPFC) of patients with mild cognitive impairment (MCI) using an advanced approach of functional connectome analysis based on network control theory (NCT). Methods: Using local-to-global functional parcellation, average and modal controllability (AC/MC) were estimated for DLPFC nodes of prefrontal-lateral control networks (R/LH_Cont_PFCl_3/4) from a resting-state fMRI series acquired at three time points (T0 = baseline, T1 = T0 + 4 weeks, T2 = T1 + 20 weeks) in MCI patients receiving regular daily sessions of 10 Hz HF-rTMS (n = 10, 68.00 ± 8.16 y, 4 males) or sham (n = 10, 63.80 ± 9.95 y, 5 males) stimulation, between T0 and T1. Longitudinal (group) effects on AC/MC were assessed with non-parametric statistics. Spearman correlations (ρ) of AC/MC vs. neuropsychological (RBANS) score %change (at T1, T2 vs. T0) were calculated. Results: AC median was reduced in MCI-rTMS, compared to the control group, for RH_Cont_PFCl_3/4 at T1 and T2 (vs. T0). In MCI-rTMS patients, for RH_Cont_PFCl_3, AC % change at T1 (vs. T0) was negatively correlated with semantic fluency (ρ = −0.7939, p = 0.045) and MC % change at T2 (vs. T0) was positively correlated with story memory (ρ = 0.7416, p = 0.045). Conclusions: HF-rTMS stimulation of DLFC nodes significantly affects the controllability of the functional connectome in MCI patients. Emerging correlations between AC/MC controllability and cognitive performance changes, immediately (T1 vs. T0) and six months (T2 vs. T0) after treatment, suggest NCT could help explain the HF-rTMS impact on prefrontal-lateral control network, monitoring induced neural plasticity effects in MCI patients.

Ye Y., Lei M., Chen L., Song R., Zhao F., Zhang L.

Technology has been increasingly integrated into controlling the decline of cognitive function. It is unclear whether technology-based cognitive and exercise interventions (T-CEIs) could generate synergistic benefits and what components would optimize this effect. This study aimed to compare the effectiveness of various T-CEIs on cognitive function in individuals with mild cognitive impairment (MCI).