UNASSIGNED: Interventions to prevent or attenuate cognitive decline and dementia in older adults are becoming increasingly important. Recently, cognitive training exercise can be via computer or mobile technology for independent or home use. Recent meta-analysis has reported that Computerized Cognitive Training (CCT) is effective at enhancing cognitive function in healthy older and Alzheimer\'s disease adults, although little is known about individual characteristics of each computerized program.
UNASSIGNED: We developed a new CCT named Brain Training Based on Everyday Living (BTEL) to enhance cognitive capacity for Instrumental Activities of Daily Living (IADL). We aim to evaluate the efficacy of the BTEL among cognitively healthy old individuals and to explore its concurrent validity and construct concept.
UNASSIGNED: We conducted a double-blind study where 106 individuals aged 65 years and older (intervened = 53, control = 53) worked on the active and placebo tasks three times a week over three months (clinical trial: UMIN000048730). The main results were examined using ANCOVA and calculating correlation coefficients.
UNASSIGNED: We found no effect on total score of the three tests; however, there was significant effect for the BTEL on: recognition in MMSE, and immediate recall in HDSR. The tasks are associated with prefrontal cortex. In addition, correlations indicated that each BTEL domain had some validity as a cognitive assessment tool. Different from previous CCT, we determined the neuropsychological characteristics of specific cognitive tasks of the BTEL to a certain degree.
UNASSIGNED: We found modest efficacy of the BTEL in cognitively healthy old individuals and confirmed its concurrent validity and the conceptual construct.

UNASSIGNED: Mild cognitive impairment (MCI), the prodromal stage of Alzheimer\'s disease, has two distinct subtypes: stable MCI (sMCI) and progressive MCI (pMCI). Early identification of the two subtypes has important clinical significance.
UNASSIGNED: We aimed to compare the cortico-striatal functional connectivity (FC) differences between the two subtypes of MCI and enhance the accuracy of differential diagnosis between sMCI and pMCI.
UNASSIGNED: We collected resting-state fMRI data from 31 pMCI patients, 41 sMCI patients, and 81 healthy controls. We chose six pairs of seed regions, including the ventral striatum inferior, ventral striatum superior, dorsal-caudal putamen, dorsal-rostral putamen, dorsal caudate, and ventral-rostral putamen and analyzed the differences in cortico-striatal FC among the three groups, additionally, the relationship between the altered FC within the MCI subtypes and cognitive function was examined.
UNASSIGNED: Compared to sMCI, the pMCI patients exhibited decreased FC between the left dorsal-rostral putamen and right middle temporal gyrus, the right dorsal caudate and right inferior temporal gyrus, and the left dorsal-rostral putamen and left superior frontal gyrus. Additionally, the altered FC between the right inferior temporal gyrus and right putamen was significantly associated with episodic memory and executive function.
UNASSIGNED: Our study revealed common and distinct cortico-striatal FC changes in sMCIs and pMCI across different seeds; these changes were associated with cognitive function. These findings can help us understand the underlying pathophysiological mechanisms of MCI and distinguish pMCI and sMCI in the early stage potentially.

UNASSIGNED: The prevalence of type 2 diabetes is increasing with the burden disproportionately falling on older adults and racial/ethnic minorities. Older adults with diabetes show greater cognitive decline and there are disparities in cognitive function by race/ethnicity that can be explained by social determinants such as wealth.
UNASSIGNED: To understand whether there is a differential relationship between wealth and cognitive function by race/ethnicity among older U.S. adults with diabetes.
UNASSIGNED: Data on 9,006 adults aged 50+ with diabetes from the Health and Retirement Study (2006-2016) were analyzed. The primary outcome, cognitive function, was a score ranging from range 0-27 categorized as: normal [12-27], mild cognitive impairment (MCI) [7-11], and dementia including Alzheimer\'s disease [0-6]. Three modeled outcomes were: 1) normal versus MCI, 2) normal versus dementia, 3) MCI versus dementia. Wealth was log transformed and used as continuous and binary (≥median, UNASSIGNED: In adjusted models, greater wealth was significantly associated with lower odds of MCI and dementia for all groups. Similarly, having wealth less than the sample median was associated with higher odds of MCI and dementia compared to wealth≥sample median.
UNASSIGNED: Increased wealth was significantly protective against MCI and dementia for all ethnic groups. Wealth less than the sample median was associated with greater odds of dementia for NHB and NHW.

BACKGROUND: With continuously aging societies, an increase in the number of people with cognitive decline is to be expected. Aside from the development of causative treatments, the successful implementation of prevention strategies is of utmost importance to reduce the high societal burden caused by neurodegenerative diseases leading to dementia among which the most common cause is Alzheimer\'s disease.
OBJECTIVE: The aim of the Luxembourgish \"programme dementia prevention (pdp)\" is to prevent or at least delay dementia in an at-risk population through personalized multi-domain lifestyle interventions. The current work aims to provide a detailed overview of the methodology and presents initial results regarding the cohort characteristics and the implementation process.
METHODS: In the frame of the pdp, an extensive neuropsychological evaluation and risk factor assessment are conducted for each participant. Based on the results, individualized multi-domain lifestyle interventions are suggested.
RESULTS: A total number of 450 participants (Mean age = 69.5 years; SD = 10.8) have been screened at different recruitment sites throughout the country, among whom 425 participants (94.4%) met the selection criteria.
CONCLUSIONS: We provide evidence supporting the feasibility of implementing a nationwide dementia prevention program and achieving successful recruitment of the target population by establishing a network of different healthcare providers.

Brain volume is associated with cognitive decline in later life, and cortical brain atrophy exceeding the normal range is related to inferior cognitive and behavioral outcomes in later life.
To investigate the likelihood of cognitive decline, mild cognitive impairment (MCI), or dementia, when regional atrophy is present in participants\' magnetic resonance imaging (MRI).
Multi-center MRI data of 2,545 adults were utilized to measure regional volumes using NEUROPHET AQUA. Four lobes (frontal, parietal, temporal, and occipital), four Alzheimer\'s disease-related regions (entorhinal, fusiform, inferior temporal, and middle temporal area), and the hippocampus in the left and right hemispheres were measured and analyzed. The presence of regional atrophy from brain MRI was defined as ≤1.5 standard deviation (SD) compared to the age- and sex-matched cognitively normal population. The risk ratio for cognitive decline was investigated for participants with regional atrophy in contrast to those without regional atrophy.
The risk ratio for cognitive decline was significantly higher when hippocampal atrophy was present (MCI, 1.84, p < 0.001; dementia, 4.17, p < 0.001). Additionally, participants with joint atrophy in multiple regions showed a higher risk ratio for dementia, e.g., 9.6 risk ratio (95% confidence interval, 8.0-11.5), with atrophy identified in the frontal, temporal, and hippocampal gray matter, than those without atrophy.
Our study showed that individuals with multiple regional atrophy (either lobar or AD-specific regions) have a higher likelihood of developing dementia compared to the age- and sex-matched population without atrophy. Thus, further consideration is needed when assessing MRI findings.

Mild cognitive impairment (MCI) is a stage between expected age-related cognitive decline and dementia. Dementias have been associated with changes in neural oscillations across the frequency spectrum, including the alpha range. Alpha is the most prominent rhythm in human EEG and is best detected during awake resting state (RS). Though several studies measured alpha power and synchronization in MCI, findings have not yet been integrated.
To consolidate findings on power and synchronization of alpha oscillations across stages of cognitive decline.
We included studies published until January 2020 that compared power or functional connectivity between 1) people with MCI and cognitively healthy older adults (OA) or people with a neurodegenerative dementia, and 2) people with progressive and stable MCI. Random-effects meta-analyses were performed when enough data was available.
Sixty-eight studies were included in the review. Global RS alpha power was lower in AD than in MCI (ES = -0.30; 95% CI = -0.51, -0.10; k = 6), and in MCI than in OA (ES = -1.49; 95% CI = -2.69, -0.29; k = 5). However, the latter meta-analysis should be interpreted cautiously due to high heterogeneity. The review showed lower RS alpha power in progressive than in stable MCI, and lower task-related alpha reactivity in MCI than in OA. People with MCI had both lower and higher functional connectivity than OA. Publications lacked consistency in MCI diagnosis and EEG measures.
Research indicates that RS alpha power decreases with increasing impairment, and could-combined with measures from other frequency bands-become a biomarker of early cognitive decline.

Alzheimer\'s disease (AD) pathological hallmarks were found in retinas of AD patients. Several studies showed a significant reduction of neuro-retina thickness measured through optical coherence tomography (OCT) in AD patients, but possible correlations between retina morphology, cognition, and cerebrospinal fluid (CSF) AD biomarkers (Aβ42, t-tau, and p-tau) have been poorly investigated so far.
In the present cross-sectional study, we measured the thickness of neuro-retinal layers through OCT searching for possible correlations with patients\' cognitive performances and CSF AD biomarkers.
137 consecutive subjects [43 with AD, 37 with mild cognitive impairment (MCI), and 57 healthy controls (HC)], received an OCT scan acquisition to measure the peripapillary retinal nerve fiber layer (RNFL) thickness. In a subsample of 21 AD, 18 MCI, and 18 HC, the macular volume of ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer was computed. A comprehensive neuropsychological assessment and CSF AD biomarkers\' concentrations were available in AD and MCI patients.
Peripapillary RNFL, global, and in superior quadrant was significantly thinner in AD and MCI patients when compared to HC, while macular GCL volume was significantly reduced only in AD. RNFL thickness in nasal and inferior quadrants was correlated with single CSF AD biomarker concentrations, but no differences were found in retina morphology depending on the presence of a CSF profile typical for AD. Memory performances were positively associated with GCL and IPL volume.
Our findings might propose OCT as a reliable and easy to handle tool able to detect neuro-retinal atrophy in AD in relation with cognitive performances.

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.
To investigate whether the R4Alz battery\'s tasks differentiate subjective cognitive decline (SCD) from cognitively healthy adults (CHA) and mild cognitive impairment (MCI).
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).
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.
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.

Differentiating mild cognitive impairment (MCI) from subjective cognitive decline (SCD) is important because of the higher progression rate to dementia for MCI and when considering future disease-modifying drugs that will have treatment indications at the MCI stage.
We examined if the two most widely-used cognitive tests, the Mini-Mental State Examination (MMSE) and clock-drawing test (CDT), and a test of attention/executive function (AQT) accurately can differentiate MCI from SCD.
We included 466 consecutively recruited non-demented patients with cognitive complaints from the BioFINDER study who had been referred to memory clinics, predominantly from primary care. They were classified as MCI (n = 258) or SCD (n = 208) after thorough neuropsychological assessments. The accuracy of MMSE, CDT, and AQT for identifying MCI was examined both in training and validation samples and in the whole population.
As a single test, MMSE had the highest accuracy (sensitivity 73%, specificity 60%). The best combination of two tests was MMSE < 27 points or AQT > 91 seconds (sensitivity 56%, specificity 78%), but in logistic regression models, their AUC (0.76) was not significantly better than MMSE alone (AUC 0.75). CDT and AQT performed significantly worse (AUC 0.71; p < 0.001-0.05); otherwise no differences were seen between any combination of two or three tests.
Neither single nor combinations of tests could differentiate MCI from SCD with adequately high accuracy. There is a great need to further develop, validate, and implement accurate screening-tests for primary care to improve accurate identification of MCI among individuals that seek medical care due to cognitive symptoms.

Alzheimer\'s disease (AD) is characterized by an involvement of brain dopamine (DA) circuitry, the presence of which has been associated with emergence of both neuropsychiatric symptoms and cognitive deficits.
In order to investigate whether and how the DA pathways are involved in the pathophysiology of AD, we assessed by in vivo neuroimaging the structural and metabolic alterations of subcortical and cortical DA pathways and targets.
We included 54 healthy control participants, 53 amyloid-positive subjects with mild cognitive impairment due to AD (MCI-AD), and 60 amyloid-positive patients with probable dementia due to AD (ADD), all with structural 3T MRI and 18F-FDG-PET scans. We assessed MRI-based gray matter reductions in the MCI-AD and ADD groups within an anatomical a priori-defined Nigrostriatal and Mesocorticolimbic DA pathways, followed by 18F-FDG-PET metabolic connectivity analyses to evaluate network-level metabolic connectivity changes.
We found significant tissue loss in the Mesocorticolimbic over the Nigrostriatal pathway. Atrophy was evident in the ventral striatum, orbitofrontal cortex, and medial temporal lobe structures, and already plateaued in the MCI-AD stage. Degree of atrophy in Mesocorticolimbic regions positively correlated with the severity of depression, anxiety, and apathy in MCI-AD and ADD subgroups. Additionally, we observed significant alterations of metabolic connectivity between the ventral striatum and fronto-cingulate regions in ADD, but not in MCI-AD. There were no metabolic connectivity changes within the Nigrostriatal pathway.
Our cross-sectional data support a clinically-meaningful, yet stage-dependent, involvement of the Mesocorticolimbic system in AD. Longitudinal and clinical correlation studies are needed to further establish the relevance of DA system involvement in AD.