A 12-month Randomised Pilot Trial of the Alzheimer’s and Music Therapy Study: A Feasibility Assessment of Music Therapy and Physical Activity in Patients with Mild-to-Moderate Alzheimer’s Disease

Background: The Alzheimer’s and Music Therapy (ALMUTH) study is the first randomised controlled trial (RCT) design with 12 months of active non-pharmacological therapy (NPT) implementing music therapy (MT) and physical activity (PA) for participants with Alzheimer’s disease (AD). The aim of the present article is to retrospectively examine the inclusion of mild-to-moderate Alzheimer’s Disease patients into the main ALMUTH study protocol and to determine if continued inclusion of AD patients is warranted. Methods: The randomised pilot trial was conducted as a parallel three-arm RCT, reflecting the experimental design of the ALMUTH study. The trial was conducted in Bergen, Norway and randomisation (1:1:1) was performed by an external researcher. The study was open label and the experimental design features two active NPTs: MT and PA, and a passive control (no intervention, CON) in Norwegian speaking patients with AD who still live at home and could provide informed consent. Sessions were offered one time per week (up to 90 minutes) up to 40 sessions over the period of 12 months. Baseline and follow-up tests included a full neuropsychological test battery and three magnetic resonance imaging (MRI) measurements (structural, functional, and diffusion weighted imaging). Feasibility outcomes were assessed and were determined as feasible if they met the target criteria. Results: 18 participants with a diagnosis of mild-to-moderate AD were screened, randomised, and tested at baseline and after a 12-month follow-up interval. Participants were divided into three groups: MT (n=6), PA (n=6), and CON (n=6). Results of the study revealed that the ALMUTH protocol in patients with AD is not feasible. Adherence to protocol was poor (50% attended sessions), the presence of 50% attrition rates, 50% retention rates, insufficient and costly recruitment, issues with study fidelity, and many issues raised by staff. Recruitment status is still ongoing and the main study has been expanded to include milder forms of memory impairment. No adverse events were reported by the patients or their caregivers. Conclusions: The pilot trial was not deemed feasible in patients exclusively with AD. To mitigate this, the ALMUTH study has expanded the recruitment criteria to include participants with milder forms of memory impairment (pre-AD) in addition to expanding the neuropsychological test battery. The ALMUTH study is currently ongoing. Trial Registration: Norsk Forskningsråd (NFR) funded. Regional Committees for Medical and Health Research Ethics (REC-WEST: reference number 2018/206). ClinicalTrials.gov: NCT03444181 (registered retrospectively 23 February 2018, https://clinicaltrials.gov/ct2/show/NCT03444181).

A Machine Learning-Based Holistic Approach to Predict the Clinical Course of Patients within the Alzheimer’s Disease Spectrum

Background: Alzheimer’s disease (AD) is a neurodegenerative condition driven by multifactorial etiology. Mild cognitive impairment (MCI) is a transitional condition between healthy aging and dementia. No reliable biomarkers are available to predict the conversion from MCI to AD. Objective: To evaluate the use of machine learning (ML) on a wealth of data offered by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Alzheimer’s Disease Metabolomics Consortium (ADMC) database in the prediction of the MCI to AD conversion. Methods: We implemented an ML-based Random Forest (RF) algorithm to predict conversion from MCI to AD. Data related to the study population (587 MCI subjects) were analyzed by RF as separate or combined features and assessed for classification power. Four classes of variables were considered: neuropsychological test scores, AD-related cerebrospinal fluid (CSF) biomarkers, peripheral biomarkers, and structural magnetic resonance imaging (MRI) variables. Results: The ML-based algorithm exhibited 86% accuracy in predicting the AD conversion of MCI subjects. When assessing the features that helped the most, neuropsychological test scores, MRI data, and CSF biomarkers were the most relevant in the MCI to AD prediction. Peripheral parameters were effective when employed in association with neuropsychological test scores. Age and sex differences modulated the prediction accuracy. AD conversion was more effectively predicted in females and younger subjects. Conclusion: Our findings support the notion that AD-related neurodegenerative processes result from the concerted activity of multiple pathological mechanisms and factors that act inside and outside the brain and are dynamically affected by age and sex.

Associations between Visual Acuity and Cognitive Decline in Older Adulthood: A 9-Year Longitudinal Study

Objective: Emerging evidence suggests low vision may be a modifiable risk factor for cognitive decline. We examined effects of baseline visual acuity (VA) on level of, and change in, cognitive test performance over 9 years. Method: A population-based sample of 1,621 participants (average age 77 years) completed a comprehensive neuropsychological evaluation and VA testing at baseline and reassessed at nine subsequent annual visits. Linear regression modeled the association between baseline VA and concurrent cognitive test performance. Joint modeling of a longitudinal sub-model and a survival sub-model to adjust for attrition were used to examine associations between baseline VA and repeated cognitive test performance over time. Results: Better baseline VA was associated cross-sectionally with younger age, male sex, greater than high school education, and higher baseline neuropsychological test scores on both vision-dependent (B coefficient range −0.163 to −0.375, p = .006 to <.001) and vision-independent tests (−0.187 to −0.215, p = .003 to .002). In longitudinal modeling, better baseline VA was associated with slower decline in vision-dependent tests (B coefficient range −0.092 to 0.111, p = .005 to <.001) and vision-independent tests (−0.107 to 0.067, p = .007 to <.001). Conclusions: Higher VA is associated with higher concurrent cognitive abilities and slower rates of decline over 9 years in both vision-dependent and vision-independent tests of memory, language, and executive functioning. Findings are consistent with emerging literature supporting vision impairment in aging as a potentially modifiable risk factor for cognitive decline. Clinicians should encourage patient utilization of vision assessment and correction with the added aim of protecting cognition.

Exploring Emotion Recognition Patterns Among Iranian People Using CANTAB as an Approved Neuro-Psychological Assessment

Background: Emotion Recognition is the main component of social cognition and has various patterns in different cultures and nationalities. The present study aimed to investigate emotion recognition patterns among Iranians using the Cambridge Neuro-Psychological Test Automated Battery (CANTAB) as a valid neuropsychological test. Methods: In this descriptive-analytical study, 117 males and females (Mage = 32.1, SD = 6.4) were initially assessed by computerised intelligence and progressive matrices of RAVEN-2. Furthermore, the excitement recognition subtest taken from the Cambridge Neuro-Psychological Test Automated Battery (CANTAB) was performed. The correct response of participants to each of the six basic emotions as well as the recognition time was used for analysis. Results: The maximum correct responses rate was 75.83% related to happy emotion. The correct responses for sadness, surprise, disgust, anger and fear were 70%, 68.48%, 47.84%, 42.54% and 38.26%, respectively. Moreover, the shortest recognition time was related to disgust with 322ms, while sadness with mean response time 1800ms and fear response time with 1529ms indicated the longest recognition time. In addition, participants recognised happiness with mean response time in 1264ms better than other emotions; however, post-hoc t-test analyses showed that only the correct responses for sadness and surprised emotions did not differ significantly, (t (112) = -.59, p = .55, d = .05). These results suggested that different emotions have various correct responses. However, sadness and surprised did not differ. Conclusions: The findings of this study could be beneficial for evaluating cognitive elements, as well as cognitive abilities and inabilities among the Iranian population. Moreover, the findings could be used for investigating social cognition in this population.

Emotional Valence Affects Word Retrieval During Verb Fluency Tasks in Alzheimer’s Dementia

Individuals with amnestic Alzheimer’s disease (AD) often demonstrate preserved emotional processing skills despite the neurodegenerative disease that affects their limbic system. Emotional valence encompasses the encoding and retrieval of memory and it also affects word retrieval in healthy populations, but it remains unclear whether these effects are preserved in individuals with amnestic AD. Previous studies used a variety of encoding procedures and different retrieval methods that resulted in mixed findings. Therefore, the purpose of the current study is to investigate whether emotional enhancement of memory effects is observed in an experimental condition where the memory encoding process is not required, namely verb (action) fluency tasks. Seventeen participants who were cognitively healthy older adults (CHOA) and 15 participants with amnestic AD were asked to complete verb fluency tasks, and the relative degree of emotional valence observed in their responses was compared between the two groups. A neuropsychological test battery was administered to determine the participants’ cognitive and linguistic profiles, and correlational analyses were conducted to delineate relationships between emotional valence, verbal memory, and learning abilities. The results indicated that the participants with amnestic AD produced words with higher emotional valence (i.e., more pleasant words) compared to CHOA during action fluency testing. In addition, the degree of emotional valence in the words was negatively correlated with verbal memory and learning skills, showing that those with poorer memory skills tend to retrieve words with higher emotional valence. The findings are consistent with those previous studies that stressed that individuals with AD have preserved emotional enhancement of memory effects and may benefit from them for retrieval of information, which may offer some insight into the development of novel rehabilitative strategies for this population.