The goal of this study was to evaluate the ability of semantic (animal naming) and phonemic (FAS) fluency in their ability to discriminate between normal aging, amnestic-Mild Cognitive Impairment (a-MCI), and Alzheimer’s disease (AD).

We used binary logistic regressions, multinomial regressions, and discriminant analysis to evaluate the predictive value of semantic and phonemic fluency in regards to specific diagnostic classifications.

Outpatient geriatric neuropsychology clinic.

232 participants (normal aging = 99, a-MCI = 90, AD = 43; mean age = 65.75 years).

Mini-mental State Examination (MMSE), Controlled Oral Word Association Test

Results indicate that semantic and phonemic fluency were significant predictors of diagnostic classification, and semantic fluency explained a greater amount of the discriminant ability of the model.

These results suggest that verbal fluency, particularly semantic fluency, may be an accurate and efficient tool in screening for early dementia in time-limited medical settings.

Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.

Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.

Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.

This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.

In medical practice, a patient’s loss of competency is a major obstacle when choosing a treatment and a starting treatment program smoothly. A large number of studies have revealed the lack of medical competency in patients with dementia. However, there have been only a few reports focusing on the capacity of patients with mild cognitive impairment (MCI) to make a medical choice.

In this study, we evaluated the competency of 40 patients with amnestic MCI (aMCI) and 33 normal subjects to make a medical choice using the MacArthur Competence Assessment Tool-Treatment (MacCAT-T). We compared the judgement of a team conference using the recorded semi-structured interview with the clinical judgement of a chief clinician.

A team conference concluded that 12 aMCI patients had no competency, and the clinical judgement, without any special interview, judged that five aMCI patients had no competency. All subjects in the control groups were judged to be competent to consent to treatment by both clinicians and the team conference.

Without supplementary tools such as explanatory documents, not a few patients with aMCI were judged by a team conference to have no competency to consent to therapy even in a relatively simple and easy case. In contrast, clinical physicians tended to evaluate the competency of aMCI patients in a generous manner.

The Visual Cognitive Assessment Test (VCAT) is a language-neutral cognitive screening tool designed for use in culturally diverse populations without the need for translations or adaptations. While it has been established to be language-neutral, the VCAT’s construct validity has not been investigated.

471 participants were recruited, comprising 233 healthy comparisons, 117 mild cognitive impairment (MCI), and 121 mild Alzheimer’s disease (AD) patients. VCAT and domain-specific neuropsychological tests were administered in the same sitting. Construct validity was assessed by analyzing domain-specific associations between the VCAT and well-established cognitive assessments. Reliability (internal consistency) was measured by Cronbach’s alpha. Diagnostic ability (area under the curve) and recommended cutoffs were determined by receiver operating characteristic (ROC) analysis.

The VCAT and its subdomains demonstrated good construct validity in terms of both convergent and divergent validity and good internal consistency (α = .74). ROC analysis found that the VCAT was on par with the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at distinguishing between healthy comparisons, MCI, and mild AD. Consistent with previous studies, VCAT scores were not affected by language of administration or ethnicity in our cohort. Findings suggest the following cutoffs: Dementia 0–19, MCI 20–24, Normal 25–30.

This study established the construct validity of the VCAT, which is vital to ensure its subdomains effectively measure the cognitive processes they were designed to. The VCAT is capable of detecting early cognitive impairments and allows for meaningful cross-cultural comparisons, especially useful for international collaborations and clinical trials, and for clinical use in diverse multiethnic populations.

Experimental studies indicate that lithium may facilitate neurotrophic/protective responses in the brain. Epidemiological and imaging studies in bipolar disorder, in addition to a few trials in Alzheimer's disease support the clinical translation of these findings. Nonetheless, there is limited controlled data about potential use of lithium to treat or prevent dementia.

To determine the benefits of lithium treatment in patients with amnestic mild cognitive impairment (MCI), a clinical condition associated with high risk for Alzheimer's disease.

A total of 61 community-dwelling, physically healthy, older adults with MCI were randomised to receive lithium or placebo (1:1) for 2 years (double-blind phase), and followed-up for an additional 24 months (single-blinded phase) (trial registration at clinicaltrials.gov: NCT01055392). Lithium carbonate was prescribed to yield subtherapeutic concentrations (0.25–0.5 mEq/L). Primary outcome variables were the cognitive (Alzheimer's Disease Assessment Scale – cognitive subscale) and functional (Clinical Dementia Rating – Sum of Boxes) parameters obtained at baseline and after 12 and 24 months. Secondary outcomes were neuropsychological test scores; cerebrospinal fluid (CSF) concentrations of Alzheimer's disease-related biomarkers determined at 0, 12 and 36 months; conversion rate from MCI to dementia (0–48 months).

Participants in the placebo group displayed cognitive and functional decline, whereas lithium-treated patients remained stable over 2 years. Lithium treatment was associated with better performance on memory and attention tests after 24 months, and with a significant increase in CSF amyloid-beta peptide (Aβ1−42) after 36 months.

Long-term lithium attenuates cognitive and functional decline in amnestic MCI, and modifies Alzheimer's disease-related CSF biomarkers. The present data reinforces the disease-modifying properties of lithium in the MCI–Alzheimer's disease continuum.

None.

To Investigate the peripheral inflammatory profile in patients with mild cognitive impairment (MCI) from three subgroups – probable Lewy body disease (probable MCI-LB), possible Lewy body disease, and probable Alzheimer’s disease (probable MCI-AD) – as well as associations with clinical features.

Memory clinics and dementia services.

Patients were classified based on clinical symptoms as probable MCI-LB (n = 38), possible MCI-LB (n = 18), and probable MCI-AD (n = 21). Healthy comparison subjects were recruited (n = 20).

Ten cytokines were analyzed from plasma samples: interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor (TNF)-alpha. C-reactive protein levels were investigated.

There was a higher level of IL-10, IL-1beta, IL-2, and IL-4 in MCI groups compared to the healthy comparison group (p < 0.0085). In exploratory analyses to understand these findings, the MC-AD group lower IL-1beta (p = 0.04), IL-2 (p = 0.009), and IL-4 (p = 0.012) were associated with increasing duration of memory symptoms, and in the probable MCI-LB group, lower levels of IL-1beta were associated with worsening motor severity (p = 0.002). In the possible MCI-LB, longer duration of memory symptoms was associated with lower levels of IL-1beta (p = 0.003) and IL-4 (p = 0.026).

There is increased peripheral inflammation in patients with MCI compared to healthy comparison subjects regardless of the MCI subtype. These possible associations with clinical features are consistent with other work showing that inflammation is increased in early disease but require replication. Such findings have importance for timing of putative therapeutic strategies aimed at lowering inflammation.

Mind-body interventions have been associated with a range of positive outcomes in older adults with mild cognitive impairment (MCI). The aim of the present study was to review the impact of different non-pharmacological programs based on mind-body intervention for older adults with MCI.

A comprehensive search method as required by the Cochrane Collaboration has been performed through the following databases: Google Scholar, Science Direct, PubMed, PsycINFO, MEDLINE, EMBASE, CINHAL, Cochrane, Ebsco. We included the studies that evaluated the impact of mind-body interventions such as mindfulness or meditation, yoga, Tai Chi and Qigong on cognitive function and everyday functionality of non-hospitalized adults aged 55 years or over with MCI.

Nine studies met the inclusion criteria. Results indicated that mind-body interventions improved cognitive function, everyday activities functioning, and mindfulness, as well as resulting in a moderate reduction in fall risk, depression and stress and lower risk of dementia at one year.

Several mind-body interventions focused broadly on mindfulness, yoga and Tai Chi training have been studied. This review shows that mind-body interventions improved cognitive function and everyday activities functioning, memory, resilience and mindfulness in older adults with MCI. However, the conclusions faced limitations, such as small sample size, heterogeneity of outcome measures, lack of an active control group and absence of long-term follow up. Further high-quality evidence is needed in order to determine whether mind-body interventions are cost-effective for improving cognitive decline in older adults with MCI and for delaying the rapid progression from MCI to Alzheimer or other types of dementia.

Disability in older adults is associated with a need for support in work, education, and community activities, reduced independence, and poorer quality of life. This study examines potential determinants of disability in a clinical sample of older adults across the continuum of cognitive decline, including sociodemographic, medical, psychiatric, and cognitive factors.

This is a cross-sectional study.

Participants were recruited from a specialty clinic for adults “at risk” of or with early dementia (including subjective cognitive complaints, mild cognitive impairment, and early dementia).

Four hundred forty-two older adults (mean age = 67.11, SD = 9.33) underwent comprehensive medical, neuropsychological, and mood assessments.

Disability was assessed via the self-report World Health Organization Disability Assessment Schedule 2.0. A stepwise (forward) linear regression model was computed to determine factors that contribute to disability within this group.

Depressive symptoms were the largest predictor, uniquely explaining 31.8% of the variance. Other contributing factors in the model included younger age, medical burden, and sleep quality, with all factors together accounting for a total of 50.4% of the variance in disability. Cognitive variables did not contribute to the model.

Depressive symptoms account for a significant portion of the variance in disability, but other factors such as age, medical burden and sleep quality are also important contributors in older adults across the continuum of cognitive decline. The relative association of these variables with disability appears to differ for older (≥65 years) relative to younger (<65 years) participants. Given the relationship between disability and these risk factors, an integrative and multidisciplinary approach to risk reduction will likely be most effective, with potential carry over effects for physical and mental health.

Despite the possibility that cognitive deficits associated with depression may have different patterns depending on the level of neurocognitive impairment, there remains no clear evidence of this. This study aimed to investigate the differential association between depression and cognitive function in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD).

A cross-sectional analysis was performed of data from 1,724 patients with MCI and 1,247 patients with AD from the Clinical Research Center for Dementia in Korea. Depression was assessed using the Korean form of the Geriatric Depression Scale, and cognition was measured using the Seoul Neuropsychological Screening Battery, which includes five domains (attention, language and related function, visuospatial function, memory, and frontal/executive function).

Significant differences were found between the two groups (non-depressed vs. depressed) in visuospatial, memory, and executive function domains in the MCI group, as well as in the attention domain in the AD group. The association between depressive symptoms and cognitive function was significantly greater in patients with MCI than in those with AD. These associations were more pronounced in memory and executive function.

Our findings suggest that the association between depression and decreased cognitive function is more pronounced in MCI than AD.

To revise an abbreviated version of the Silhouettes subtest of the Visual Object and Space Perception (VOSP) battery in order to recognize mild cognitive impairment (MCI) and determine the optimal cutoffs to differentiate among cognitively normal controls (NC), MCI, and Alzheimer’s Disease (AD) in the Chinese elderly.

A cross-sectional validation study.

Huashan Hospital, Shanghai, China.

A total of 591 participants: Individuals with MCI (n = 211), AD (n = 139) and NC (n = 241) were recruited from the Memory Clinic, Huashan Hospital, Shanghai, China.

Baseline neuropsychological battery (including VOSP) scores were collected from firsthand data. An abbreviated version of silhouettes test (Silhouettes-A) was revised from the original English version more suitable for the elderly, including eight silhouettes of animals and seven silhouettes of inanimate objects, with a score ranging from 0 to 15.

Silhouettes-A was an effective test to screen MCI in the Chinese elderly with good sensitivity and specificity, similar to the Montreal cognitive assessment and superior to other single tests reflecting language, spatial, or executive function. However, it had no advantage in distinguishing MCI from AD. The corresponding optimal cutoff scores of Silhouettes-A were 10 for screening MCI and 8 for AD.

Silhouettes-A is a quick, simple, sensitive, and dependable cognitive test to distinguish among NC, MCI, and AD patients.

In a previous study, we developed a highly performant and clinically-translatable machine learning algorithm for a prediction of three-year conversion to Alzheimer’s disease (AD) in subjects with Mild Cognitive Impairment (MCI) and Pre-mild Cognitive Impairment. Further tests are necessary to demonstrate its accuracy when applied to subjects not used in the original training process. In this study, we aimed to provide preliminary evidence of this via a transfer learning approach.

We initially employed the same baseline information (i.e. clinical and neuropsychological test scores, cardiovascular risk indexes, and a visual rating scale for brain atrophy) and the same machine learning technique (support vector machine with radial-basis function kernel) used in our previous study to retrain the algorithm to discriminate between participants with AD (n = 75) and normal cognition (n = 197). Then, the algorithm was applied to perform the original task of predicting the three-year conversion to AD in the sample of 61 MCI subjects that we used in the previous study.

Even after the retraining, the algorithm demonstrated a significant predictive performance in the MCI sample (AUC = 0.821, 95% CI bootstrap = 0.705–0.912, best balanced accuracy = 0.779, sensitivity = 0.852, specificity = 0.706).

These results provide a first indirect evidence that our original algorithm can also perform relevant generalized predictions when applied to new MCI individuals. This motivates future efforts to bring the algorithm to sufficient levels of optimization and trustworthiness that will allow its application in both clinical and research settings.

To compare the accuracy of Mini-Mental State Examination (MMSE) and of the Montreal Cognitive Assessment (MoCA) in tracking mild cognitive impairment (MCI) and Alzheimer’s Disease (AD).

A Systematic review of the PubMed, Bireme, Science Direct, Cochrane Library, and PsycInfo databases was conducted. Using inclusion and exclusion criteria and staring with 1,629 articles, 34 articles were selected. The quality of the selected research was evaluated through the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2).

More than 80% of the articles showed MoCA to be superior to MMSE in discriminating between individuals with mild cognitive impairment and no cognitive impairment. The area under the curve varied from 0.71 to 0.99 for MoCA, and 0.43 to 0.94 for MMSE, when evaluating the ability to discriminate MCI in the cognitively healthy elderly individuals, and 0.87 to 0.99 and 0.67 to 0.99, respectively, when evaluating the detection of AD. The AUC mean value for MoCA was significantly larger compared to the MMSE in discriminating MCI from control [0.883 (CI 95% 0.855-0.912) vs MMSE 0.780 (CI 95% 0.740-0.820) p < 0.001].

The screening tool MoCA is superior to MMSE in the identification of MCI, and both tests were found to be accurate in the detection of AD.

To investigate whether amnestic mild cognitive impairment (aMCI) identified with visual memory tests conveys an increased risk of Alzheimer’s disease (risk-AD) and if the risk-AD differs from that associated with aMCI based on verbal memory tests.

4,771 participants aged 70.76 (SD = 6.74, 45.4% females) from five community-based studies, each a member of the international COSMIC consortium and from a different country, were classified as having normal cognition (NC) or one of visual, verbal, or combined (visual and verbal) aMCI using international criteria and followed for an average of 2.48 years. Hazard ratios (HR) and individual patient data (IPD) meta-analysis analyzed the risk-AD with age, sex, education, single/multiple domain aMCI, and Mini-Mental State Examination (MMSE) scores as covariates.

All aMCI groups (n = 760) had a greater risk-AD than NC (n = 4,011; HR range = 3.66 – 9.25). The risk-AD was not different between visual (n = 208, 17 converters) and verbal aMCI (n = 449, 29 converters, HR = 1.70, 95%CI: 0.88, 3.27, p = 0.111). Combined aMCI (n = 103, 12 converters, HR = 2.34, 95%CI: 1.13, 4.84, p = 0.023) had a higher risk-AD than verbal aMCI. Age and MMSE scores were related to the risk-AD. The IPD meta-analyses replicated these results, though with slightly lower HR estimates (HR range = 3.68, 7.43) for aMCI vs. NC.

Although verbal aMCI was most common, a significant proportion of participants had visual-only or combined visual and verbal aMCI. Compared with verbal aMCI, the risk-AD was the same for visual aMCI and higher for combined aMCI. Our results highlight the importance of including both verbal and visual memory tests in neuropsychological assessments to more reliably identify aMCI.