Subjective Cognitive Impairment Can Be Detected from the Decline of Complex Cognition: Findings from the Examination of Remedes 4 Alzheimer's (R4Alz) Structural Validity.

R4Alz is utilized for the early detection of minor neurocognitive disorders. It was designed to assess three main dimensions of cognitive-control abilities: working-memory capacity, attentional control, and executive functioning. OBJECTIVES: To reveal the cognitive-control dimensions that can differentiate between adults and older adults with healthy cognition, people with subjective cognitive impairment, and people diagnosed with mild cognitive impairment by examining the factorial structure of the R4Alz tool. METHODS: The study comprised 404 participants: (a) healthy adults (n = 192), (b) healthy older adults (n = 29), (c) people with SCI (n = 74), and (d) people diagnosed with MCI (n = 109). The R4Alz battery was administered to all participants, including tests that assess short-term memory storage, information processing, information updating in working memory, and selective, sustained and divided attention), task/rule-switching, inhibitory control, and cognitive flexibility. RESULTS: A two-factorial structural model was confirmed for R4Alz, with the first factor representing "fluid intelligence (FI)" and the second factor reflecting "executive functions (EF)". Both FI and EFs discriminate among all groups. CONCLUSIONS: The R4Alz battery presents sound construct validity, evaluating abilities in FI and EF. Both abilities can differentiate very early cognitive impairment (SCI) from healthy cognitive aging and MCI.

Metacognitive Strategy Training Improves Decision-Making Abilities in Amnestic Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is associated with deficits in decision-making, which is of utmost importance for daily functioning. Despite evidence of declined decision-making abilities, research on decision-making interventions for MCI is scarce. As metacognition seems to play an important role in decision-making, the present study's aim was to examine whether a metacognitive strategy training can improve MCI patients' decision-making abilities. Older adults-patients of a day care center, diagnosed with amnestic MCI (n = 55) were randomly allocated in two groups, which were matched in gender, age and educational level. Τhe experimental group (n = 27, 18 women, mean age = 70.63, mean years of education = 13.44) received the metacognitive strategy training in parallel with the cognitive and physical training programs of the day care center, and the active control group (n = 28, 21 women, mean age = 70.86, mean years of education = 13.71) received only the cognitive and physical training of the center. The metacognitive strategy training included three online meeting sessions that took place once per week. The basis of the intervention was using analytical thinking, by answering four metacognitive-strategic questions, to make decisions about everyday situations. To examine the efficacy of the training, the ability to make decisions about everyday decision-making situations and the ability to apply decision rules were measured. Both groups participated in a pre-test session and a post-test session, while the experimental group also participated in a follow-up session, one month after the post-test session. The results showed that the experimental group improved its ability to decide, based on analytical thinking, about economic and healthcare-related everyday decision-making situations after they received the metacognitive strategy training. This improvement was maintained one month later. However, the ability to apply decision rules, which requires high cognitive effort, did not improve. In conclusion, it is important that some aspects of the analytical decision-making ability of amnestic MCI patients were improved due to the present metacognitive intervention.

A Confirmatory and an Exploratory Factor Analysis of the Cohen-Mansfield Agitation Inventory (CMAI) in a European Case Series of Patients with Dementia: Results from the RECage Study.

BACKGROUND: One of the most widely used instruments for assessing agitation in dementia patients is the Cohen-Mansfield Agitation Inventory (CMAI), nevertheless no global score has been proposed. The aim of this study is: (a) to conduct a confirmatory (CFA) and exploratory factor analysis (EFA) of CMAI on people with dementia and Psychological and Behavioral Symptoms (BPSD), and (b) to propose an alternative structure, based on clinical criteria including all CMAI items. METHODS: Confirmatory and exploratory factor analyses were carried out on the CMAI 29 items administered at baseline to 505 patients with dementia (PwD) and BPSD enrolled in the international observational RECage study. RESULTS: The three-factor structure has not been confirmed by the CFA, whilst the EFA was carried out respectively on 25 items disregarding 4 items with a prevalence ≤5% and then on 20 items disregarding 9 items with a prevalence ≤10%. The four-factor structure explaining 56% of the variance comprised Physically Aggressive behavior, Verbally Aggressive behavior, Physically non-aggressive behavior, and Physically and verbally aggressive behavior. CONCLUSIONS: A new grouping of all items according to a clinical criterion is proposed, allowing for a more sensible evaluation of the symptoms leading to better differentiation.

R4Alz-Revised: A Tool Able to Strongly Discriminate 'Subjective Cognitive Decline' from Healthy Cognition and 'Minor Neurocognitive Disorder'.

BACKGROUND: The diagnosis of the minor neurocognitive diseases in the clinical course of dementia before the clinical symptoms' appearance is the holy grail of neuropsychological research. The R4Alz battery is a novel and valid tool that was designed to assess cognitive control in people with minor cognitive disorders. The aim of the current study is the R4Alz battery's extension (namely R4Alz-R), enhanced by the design and administration of extra episodic memory tasks, as well as extra cognitive control tasks, towards improving the overall R4Alz discriminant validity. METHODS: The study comprised 80 people: (a) 20 Healthy adults (HC), (b) 29 people with Subjective Cognitive Decline (SCD), and (c) 31 people with Mild Cognitive Impairment (MCI). The groups differed in age and educational level. RESULTS: Updating, inhibition, attention switching, and cognitive flexibility tasks discriminated SCD from HC (p ≤ 0.003). Updating, switching, cognitive flexibility, and episodic memory tasks discriminated SCD from MCI (p ≤ 0.001). All the R4Alz-R's tasks discriminated HC from MCI (p ≤ 0.001). The R4Alz-R was free of age and educational level effects. The battery discriminated perfectly SCD from HC and HC from MCI (100% sensitivity-95% specificity and 100% sensitivity-90% specificity, respectively), whilst it discriminated excellently SCD from MCI (90.3% sensitivity-82.8% specificity). CONCLUSION: SCD seems to be stage a of neurodegeneration since it can be objectively evaluated via the R4Alz-R battery, which seems to be a useful tool for early diagnosis.

Examining Voting Capacity in Older Adults with and without Cognitive Decline.

BACKGROUND: Nowadays, controversy exists regarding the stage of cognitive decline and/or dementia where voting capacity is diminished. AIM: To evaluate whether general cognitive status in advancing age predicts voting capacity in its specific aspects. METHODS: The study sample comprised 391 people: 88 cognitively healthy older adults (CH), 150 people with Mild Cognitive Impairment (MCI), and 153 people with Alzheimer's disease dementia (ADD). The assessment included CAT-V for the voting capacity and Mini Mental State Examination (MMSE) for general cognitive ability. ANOVAs and ROC curves were the tools of statistical analysis towards (a) indicating under which MMSE rate participants are incapable of voting and (b) whether the CAT-V total score can discriminate people with dementia (PwADD) from people without dementia (PwtD). RESULTS: Out of the six CAT-V questions, one question was associated with a low MMSE cutoff score (19.50), having excellent sensitivity (92.5%) and specificity (77.20%), whilst the other five questions presented a higher MMSE cutoff score, with a good sensitivity (78.4% to 87.6%) and specificity (75.3% to 81.7%), indicating that voting difficulties are associated with cognitive status. Secondarily, the total CAT-V score discriminates PwADD from PwtD of 51-65 years (sensitivity 93.2%/specificity 100%-excellent), PwADD from PwtD of 66-75 years (sensitivity 73.3%/specificity 97.1%-good), PwADD from PwtD of 76-85 years (sensitivity 92.2%/specificity 64.7%-good), whilst for 86-95 years, a cutoff of 9.5 resulted in perfect sensitivity and specificity (100%). CONCLUSION: According to MMSE, PwADD have no full voting competence, whilst PwtD seem to have intact voting capacity. The calculated cut-off scores indicate that only people who score more than 28 points on the MMSE have voting capacity.

Longitudinal Cognitive and Physical Training Effectiveness in MCI, Based on the Experience of the Alzheimer's Hellas Day Care Centre.

This study assesses the effectiveness of a multicomponent Longitudinal Cognitive Training (CT) program plus physical exercise (PE) for people with Mild Cognitive Impairment (MCI). 155 people with MCI, completed a 3 years (3Y) CT+PE, whilst 133 were control. Neuropsychological assessment was performed at baseline and 3 years later, whilst CT+PE had additional annual assessments. According to the results, the 3Y CT+PE outperformed control in cognitive abilities (p < 0.002), and Activities of Daily Living (ADL) (p < 0.001), stabilized their functional performances between 1st and 2nd year, but worsened in working and verbal memory between 2nd and 3 rd year (p < 0.002). Control deteriorated in cognitive functions (p < 0.001) and ADL (p < 0.001) after 3 years, whilst 1.33% of the experimental and 13.53% of the control group progressed to dementia (p < 0.001). Longitudinal CT+PE improves cognitive performance and ADL in MCI and delay the progression to dementia.

Are There Any Cognitive and Behavioral Changes Potentially Related to Quarantine Due to the COVID-19 Pandemic in People with Mild Cognitive Impairment and AD Dementia? A Longitudinal Study.

The aim of the study was to examine potential cognitive, mood (depression and anxiety) and behavioral changes that may be related to the quarantine and the lockdown applied during the COVID-19 pandemic in Greek older adults with mild cognitive impairment (MCI), and AD dementia in mild and moderate stages. METHOD: 407 older adults, diagnosed either with MCI or AD dementia (ADD), were recruited from the Day Centers of the Greek Association of Alzheimer Disease and Related Disorders (GAADRD). Neuropsychological assessment was performed at baseline (at the time of diagnosis) between May and July of 2018, as well as for two consecutive follow-up assessments, identical in period, in 2019 and 2020. The majority of participants had participated in non-pharmacological interventions during 2018 as well as 2019, whereas all of them continued their participation online in 2020. RESULTS: Mixed measures analysis of variance showed that participants' 'deterioration difference-D' by means of their performance difference in neuropsychological assessments between 2018-2019 (D1) and 2019-2020 (D2) did not change, except for the FUCAS, RAVLT, and phonemic fluency tests, since both groups resulted in a larger deterioration difference (D2) in these tests. Additionally, three path models examining the direct relationships between performance in tests measuring mood, as well as everyday functioning and cognitive measures, showed that participants' worsened performance in the 2019 and 2020 assessments was strongly affected by NPI performance, in sharp contrast to the 2018 assessment. DISCUSSION: During the lockdown period, MCI and ADD patients' neuropsychological performance did not change, except from the tests measuring verbal memory, learning, and phonemic fluency, as well as everyday functioning. However, the natural progression of the MCI as well as ADD condition is the main reason for participants' deterioration. Mood performance became increasingly closely related to cognition and everyday functioning. Hence, the role of quarantine and AD progression are discussed as potential factors associated with impairments.

Memory Clinics and Day Care Centers in Thessaloniki, Northern Greece: 30 Years of Clinical Practice and Experience.

Background: This review describes the diagnostic and interventional procedures conducted in two university memory clinics (established network of G. Papanikolaou Hospital: 1988-2017 and AHEPA hospital: 2017-today) and 2 day care centers (established network of DCCs: 2005-today) in North Greece and their contribution in the scientific field of dementia. The aims of this work are (1) to provide a diagnosis and treatment protocol established in the network of memory clinics and DCCs and (2) to present further research conducted in the aforementioned network during the last 30 years of clinical practice. Methods: The guidelines to set a protocol demand a series of actions as follows: (1) set the diagnosis criteria, neuropsychological assessment, laboratory examinations, and examination of neurophysiological, neuroimaging, cerebrospinal fluid, blood, and genetic markers; and (2) apply non-pharmacological interventions according to the needs and specialized psychosocial interventions of the patient to the caregivers of the patient. Results: In addition to the guidelines followed in memory clinics at the 1st and 3rd Department of Neurology and two DCCs, a database of patients, educational programs, and further participation in international research programs, including clinical trials, make our contribution in the dementia field strong. Conclusion: In the current paper, we provide useful guidelines on how major and minor neurocognitive disorders are being treated in Thessaloniki, Greece, describing successful practices which have been adapted in the last 30 years.

Discriminant Validity of the WAIS-R Digit Symbol Substitution Test in Subjective Cognitive Decline, Mild Cognitive Impairment (Amnestic Subtype) and Alzheimer's Disease Dementia (ADD) in Greece.

OBJECTIVE: The aim of the current study was to estimate the discriminant potential and validity of the Digit Symbol Substitution Test (DSST) of the WAIS-R in the Greek elderly population meeting criteria for subjective cognitive decline (SCD), mild cognitive impairment (aMCI; amnestic subtype), or Alzheimer's disease dementia (ADD). METHOD: Four hundred eighty-eight community-dwelling older adults, visitors of the Day Center of Alzheimer Hellas, participated in the study. Two hundred forty-three of them met the criteria for ADD, one hundred eighty-two for aMCI and sixty-three for SCD. RESULTS: Path analysis indicated that the DSST score is affected by age group, educational level, and diagnostic category, but is not affected by gender. The ROC curve analysis showed that the DSST sum score could perfectly differentiate SCD from ADD patients, whereas test's discriminant potential between aMCI and dementia ADD's subtype was satisfactory. However, DSST was unable to separate the SCD from the aMCI group. CONCLUSION: It appears that the DSST is unable to separate the SCD from aMCI population. Therefore, the test in question may be insensitive to incipient cognitive decline. On the contrary, the discriminant potential of the DSST as regards SCD and ADD is excellent, while discrimination between aMCI and ADD is good.

Rationale, Design, and Methodology of a Prospective Cohort Study for Coping with Behavioral and Psychological Symptoms of Dementia: The RECage Project.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are quite challenging problems during the dementia course. Special Care Units for people with dementia (PwD) and BPSD (SCU-B) are residential medical structures, where BPSD patients are temporarily admitted, in case of unmanageable behavioral disturbances at home. OBJECTIVE: RECage (REspectful Caring for AGitated Elderly) aspires to assess the short and long-term effectiveness of SCU-Bs toward alleviating BPSD and improving the quality of life (QoL) of PwD and their caregivers. METHODS: RECage is a three-year, prospective study enrolling 500 PwD. Particularly, 250 community-dwelling PwDs presenting with severe BPSD will be recruited by five clinical centers across Europe, endowed with a SCU-B, for a short period of time; a second similar group of 250 PwD will be followed by six other no-SCU-B centers solely via outpatient visits. RECage's endpoints include short and long-term SCU-B clinical efficacy, QoL of patients and caregivers, cost-effectiveness of the SCU-B, psychotropic drug consumption, caregivers' attitude toward dementia, and time to nursing home placement. RESULTS: PwD admitted in SCU-Bs are expected to have diminished rates of BPSD and better QoL and their caregivers are also expected to have better QoL and improved attitude towards dementia, compared to those followed in no-SCU-Bs. Also, the cost of care and the psychotropic drug consumption are expected to be lower. Finally, PwD followed in no-SCU-Bs are expected to have earlier admission to nursing homes. CONCLUSION: The cohort study results will refine the SCU-B model, issuing recommendations for implementation of SCU-Bs in the countries where they are scarce or non-existent.

Is the Discrimination of Subjective Cognitive Decline from Cognitively Healthy Adulthood and Mild Cognitive Impairment Possible? A Pilot Study Utilizing the R4Alz Battery.

BACKGROUND: The early diagnosis of neurocognitive disorders before the symptoms' onset is the ultimate goal of the scientific community. REMEDES for Alzheimer (R4Alz) is a battery, designed for assessing cognitive control abilities in people with minor and major neurocognitive disorders. OBJECTIVE: To investigate whether the R4Alz battery's tasks differentiate subjective cognitive decline (SCD) from cognitively healthy adults (CHA) and mild cognitive impairment (MCI). METHODS: The R4Alz battery was administered to 175 Greek adults, categorized in five groups a) healthy young adults (HYA; n = 42), b) healthy middle-aged adults (HMaA; n = 33), c) healthy older adults (HOA; n = 14), d) community-dwelling older adults with SCD (n = 34), and e) people with MCI (n = 52). RESULTS: Between the seven R4Alz subtasks, four showcased the best results for differentiating HOA from SCD: the working memory updating (WMCUT-S3), the inhibition and switching subtask (ICT/RST-S1&S2), the failure sets (FS) of the ICT/RST-S1&S2, and the cognitive flexibility subtask (ICT/RST-S3). The total score of the four R4Alz subtasks (R4AlzTot4) leads to an excellent discrimination among SCD and healthy adulthood, and to fare discrimination among SCD and MCI. CONCLUSION: The R4Alz battery is a novel approach regarding the neuropsychological assessment of people with SCD, since it can very well assist toward discriminating SCD from HOA. The R4Alz is able to measure decline of specific cognitive control abilities - namely of working memory updating, and complex executive functions - which seem to be the neuropsychological substrate of cognitive complaints in community dwelling adults of advancing age.

REMEDES for Alzheimer-R4Alz Battery: Design and Development of a New Tool of Cognitive Control Assessment for the Diagnosis of Minor and Major Neurocognitive Disorders.

BACKGROUND: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are acknowledged stages of the clinical spectrum of Alzheimer's disease (AD), and cognitive control seems to be among the first neuropsychological predictors of cognitive decline. Existing tests are usually affected by educational level, linguistic abilities, cultural differences, and social status, constituting them error-prone when differentiating between the aforementioned stages. Creating robust neuropsychological tests is therefore prominent. OBJECTIVE: The design of a novel psychometric battery for the cognitive control and attention assessment, free of demographic effects, capable to discriminate cognitively healthy aging, SCD, MCI, and mild Dementia (mD). METHODS: The battery initial hypothesis was tuned using iterations of administration on random sampling healthy older adults and people with SCD, MCI, and mD, from the area of Thessaloniki, Greece. This resulted in the first release of the REflexes MEasurement DEviceS for Alzheimer battery (REMEDES for Alzheimer-R4Alz). RESULTS: The first release lasts for almost an hour. The battery was design to assess working memory (WM) including WM storage, processing, and updating, enriched by episodic buffer recruitment. It was also designed to assess attention control abilities comprising selective, sustained, and divided attention subtasks. Finally, it comprises an inhibitory control, a task/rule switching or set-shifting, and a cognitive flexibility subtask as a combination of inhibition and task/rule switching abilities. CONCLUSION: The R4Alz battery is an easy to use psychometric battery with increasing difficulty levels and assumingly ecological validity, being entertaining for older adults, potentially free of demographic effects, and promising as a more accurate and early diagnosis tool of neurodegeneration.

Normative Data for the Montreal Cognitive Assessment in Greek Older Adults With Subjective Cognitive Decline, Mild Cognitive Impairment and Dementia.

OBJECTIVE: The aim of the study was to provide normative data for the MoCA in a Greek cohort of people older than 60 years who meet criteria for subjective cognitive decline (SCD), mild cognitive impairment (MCI), or dementia in order to optimize cutoff scores for each diagnostic group. METHOD: Seven hundred forty-six community-dwelling older adults, visitors of the Day Center of Alzheimer Hellas were randomly chosen. Three hundred seventy-nine of them met the criteria for dementia, 245 for MCI and 122 for SCD. RESULTS: Initial statistical analyses showed that the total MoCA score is not affected by gender (P = .164), or age (P = .144) but is affected by educational level (P < .001). A cutoff score of 23 for low educational level (≤6 years) can distinguish people with SCD from MCI (sensitivity 71.4%, specificity 84.2%), while 26 is the cutoff score for middle educational level (7-12 years; sensitivity 73.2%, specificity 67.0%) and high educational level (≥13 years; sensitivity 77.6%, specificity 74.7%). Montreal Cognitive Assessment can discriminate older adults with SCD from dementia, with a cutoff score of 20 for low educational level (sensitivity 100%, specificity 92.3%) and a cutoff score 23 for middle educational level (sensitivity 97.6%, specificity 92.7%) and high educational level (sensitivity 98.5%, specificity 100%). CONCLUSION: Montreal Cognitive Assessment is not affected by age or gender but is affected by the educational level. The discriminant potential of MoCA between SCD and MCI is good, while the discrimination of SCD from dementia is excellent.

A Comparative Single-Blind Randomized Controlled Trial With Language Training in People With Mild Cognitive Impairment.

BACKGROUND: Although cognitive training is effective for people with mild cognitive impairment (MCI), it is not clear which format is more effective. OBJECTIVE: To compare the effectiveness of the same language programs when carried out via computer, paper/pencil and orally in people with MCI. METHODS: Seventy-one participants with MCI were randomly classified in 3 experimental and 2 control groups. The experimental groups attended 48 sessions of language training for 6 months. The control groups attended either unstructured sessions or they were on waiting list. RESULTS: Mixed measures analysis of variance, at the follow-up, showed a significant cognitive abilities improvement among the experimental versus control groups. At the end of the language training, the 3 groups presented improvement in cognitive abilities and daily function, while the control groups remained at the same performance level. CONCLUSION: All 3 cognitive language training methods were equally significantly effective.

The operation of the Day Care Centre of Alzheimer Hellas "Saint Helen" and of the Memory Clinic of Papanikolaou General Hospital from 2007 to 2017.

OBJECTIVE: Nowadays, there is a rapid increase of neurocognitive disorders (ND), while Alzheimer disease (AD), is the most frequent type of neurodegeneration. Therefore, Day Care Centers (DCC) and Memory Clinics (MC) have been created in order to correspond to the rising needs of people with ND. The aim of the study was to record clinical and demographic characteristics of people with ND from the broader area of Thessaloniki. SUBJECTS AND METHODS: Data bases were collected and were analyzed in order to examine demographical characteristics of all visitors of the DCC of Alzheimer Hellas and of visitors of the Papanikolaou General Hospital, during the years 2007-2017. Six thousand and ninety six people (N=6.096) were totally classified as single visitors of the outpatients of MC of Papanikolaou General Hospital and of the DCC of Alzheimer Hellas. RESULTS: Among the total number of visitors, 3.078 people received the diagnosis of Mild Cognitive Impairment (MCI), whereas 3.018 people met the dementia diagnosis criteria. As far as the MCI group is concerned, the majority of them were women (72.1%) while the mean age of MCI group was M (SD)=67.73(9.21) years. Their mean education was M (SD)=10.65 (4.59) years, while their mean score in general cognitive performance (MMSE) was M (SD)=27.03(2.18) points and their score of general functional performance (FUCAS) was M (SD)=44.32(2.49). In regards to the dementia group, the majority of them were also women (63.8%) with a mean age M (SD)=76.08 (8.60) years and a mean education M (SD)=7.35 (4.41) years. The MMSE score of the group was M (SD)=17.79 (6.53) and the FUCAS score was M (SD)=63.25 (18.12). Moreover, the vast majority of dementia type was AD (53.1%). CONCLUSION: Women are presented more frequently to primary care services and people with dementia have lower education and greater age. AD continues to be the most common type of dementia.

Effectiveness of nonpharmacological approaches in patients with mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) patients are at increased risk of developing dementia. There is a conflict if cognitive interventions can improve cognitive and functional performances in order to delay the development of dementia. OBJECTIVES: This study aimed to examine the effectiveness of a holistic cognitive rehabilitation program on patients with MCI. METHODS: The participants, 176 MCI patients with Mini-Mental State Examination = 27.89 (1.73), were classified into 2 groups matched for age, gender, education and cognitive abilities: (1) patients (104) on nonpharmacological therapy and (2) patients (72) on no therapy at all. The effectiveness of the interventions was assessed by neuropsychological evaluation performed at baseline and at the end of the interventions. RESULTS: Between-group difference in benefit of the experimental group was demonstrated in abilities of executive function (p = 0.004), verbal memory (p = 0.003), praxis (p ≤ 0.012), daily function (p = 0.001) and general cognitive ability (p ≤ 0.005). The experimental patients improved cognitive and functional performances, while the control patients demonstrated deterioration in daily function (p = 0.004). CONCLUSIONS: Our findings indicate that nonpharmacological therapy of the holistic approach can improve MCI patients' cognitive and functional performances.