The effect of moxibustion on brain functional connectivity and effective brain networks in patients with amnestic mild cognitive impairment: study protocol for a randomized controlled trial and preliminary results

Objective To identify the differences inneuropsychological characteristics between amnestic(AMCI)and vascular mild cognitive impairment(VMCI). Methods Totally 297 old community residents with mild cognitive impairment(MCI)were divided into amnestic MCI(AMCI)and vascular MCI(VMCI)subgroup from Guangzhou MCI prevalence survey.The elderly with MCI were interviewed and tested with the Chinese version of Montreal Cognitive Assessment(MoCA), the Mini-Mental state examination(MMSE), Auditory Verbal Learning Test(AVLT), the Clinical Dementia Rating scale(CDR), Functional Activity Questionnaire(FAQ), the Modified Hachinski Ischemic Scale(M-HIS), Center for Epidemiologic Studies(CES-DC)to evaluate neuropsychological characteristics. Results AMCI versus VMCI group showed that the total scores of MoCA were(9.63±5.17 vs.9.98±6.02), total scores of MMSE were(16.90±4.84 vs.16.90±6.19), AVLT immediate memory was(2.35±1.39 vs.2.91±1.84), AVLT delayed recall was(2.23±2.09 vs.2.47±2.20), AVLT delayed recognition was(7.33±3.98 vs.6.85±4.02)and total scores of CDR(0.5 vs.0.5), with no differences between the 2 groups(all P>0.05). Based on MoCA survey, AMCI versus VMCI group showed statistically significant differences(all P<0.05)in parameters of visual space and execution(0.71±1.02 vs.0.92±1.26), language function(0.34±0.56 vs.0.50±0.80)and abstract thinking(0.25±0.49 vs.0.15±0.43), but based on MMSE survey, no difference was found in the various cognitive domains between the two groups.The AMCI versus VMCI group showed statistically significant differences(all P<0.05)in parameters of CES-DC scale(1.75±4.27 vs.2.76±6.72), FAQ scale(4.42±4.66 vs.8.71±7.03), M-HIS scale(0.40±0.64 vs.7.59±3.53). Conclusions There is no significant difference in general cognitive impairment between AMCI and VMCI, but the visual space and execution, language function are more impaired in AMCI than VMCI, and the abstract thinking, social function are more impaired with more depressive symptoms in VMCI than in AMCI. Key words: Cognition disorders; Neuropsychological tests; Amnesia; Blood vessels

Background: Mild cognitive impairment (MCI) is a heterogeneous condition with a variety of clinical outcomes, the presence of which correlates with risk of Alzheimer’s disease as well as pre-clinical stages of other dementia subtypes. The aims of this study were to assess the specific patterns of cognitive profiles and to identify changes from baseline to 24 weeks in patients with MCI using detailed neuropsychological testing. Methods: We consecutively recruited 120 MCI patients at baseline according to the Petersen’s clinical diagnostic criteria, who were admitted to the Dementia and Memory Clinics. We analyzed patients who fulfilled both inclusion and exclusion criteria for MCI and classified them into four subtypes according to deficits in major cognitive domains; amnestic MCI single domain (aMCI-s), amnestic multiple domain MCI (aMCI-m), non-amnestic single domain MCI (naMCI-s) and non-amnestic multiple domain MCI (naMCI-m). Four groups of MCI were evaluated by a detailed neuropsychological battery test. Results: 83 patients with MCI at the 24-week follow-up were classified into four subtypes. The most frequent subtype was amnestic multi-domain MCI, with the frequency of MCI subtypes as follows: aMCI-s (n = 21, 25.3%), aMCI-m (n = 53, 63.9%), naMCI-s (n = 5, 6.0%) and naMCI-m (n = 4, 4.8%). In the major cognitive items of the SNSB-D, there were significant changes between the initial and follow-up tests in the domains of language, memory and the fron-tal/executive function (p < 0.05), except for attention, in all MCI patient subtypes. At 24-weeks follow-up, the conversion rate to Alzheimer’s disease was 2.4% (n = 2) from a subtype of amnestic multi-domain MCI. Conclusions: Our study revealed the most frequent subtype of MCI to be multiple domain amnestic MCI, with this subtype having a higher tendency of conversion to Alzheimer’s disease.

This study aimed to evaluated the clinical impact of adding [11C] Pittsburgh compound-B (11C-PiB) PET for clinical diagnosis of mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia.Twenty six (mean age 78.5 ± 5.18 years, 21 females) AD (n = 7), amnestic MCI (n = 12), non-amnestic MCI (n = 3), vascular dementia, progressive supranuclear palsy (PSP) with frontotemporal dementia (FTD), FTD (n = 1 each), and normal (n = 1) patients underwent 11C-PiB-PET, MRI, and SPECT scanning. 11C-PiB-PET was compared with MRI and SPECT for clinical impact.11C-PiB-PET showed positivity in 6, 9, and 0 of the AD, amnestic MCI, and non-amnestic MCI patients, respectively, and 0 of those with another disease. Parahippocampal atrophy at VSASD was observed in 5 AD patients, 6 amnestic and PiB-positive MCI patients, 1 amnestic and PiB-negative MCI patient, and 1 vascular dementia patient. Parietal lobe hypoperfusion in SPECT findings was observed in 6, 4, and 2 of those, respectively, as well as 1 each of non-amnestic MCI, vascular dementia, and normal cases. Sensitivity/specificity/accuracy for selecting PiB-positive patients among the 15 MCI patients for 11C-PiB-PET were 100% (9/9)/100% (6/6)/100% (15/15), for VSRAD were 66.7% (6/9)/83.3% (5/6)/73.3% (11/15), and for SPECT were 44.4% (4/9)/50.0% (3/6)/46.7% (7/15), while those were 88.9% (8/9)/33.3% (2/6)/66.7% (10/15)/for combined VSRAD and SPECT. 11C-PiB-PET accuracy was significantly higher than that of SPECT.11PiB-PET alone may be useful for selecting patients who will progress from MCI to AD in the future, although follow-up study is necessary to clarify the outcome of MCI patients.

Dual-task gait performance is impaired in older adults with mild cognitive impairment, but the brain substrates associated with dual-task gait performance are not well-established. The relationship between gray matter and gait speed under single-task and dual-task conditions (walking while counting backward) was examined in 560 seniors with mild cognitive impairment (non-amnestic mild cognitive impairment: n=270; mean age=72.4yrs., 63.6% women; amnestic mild cognitive impairment: n=290; mean age=73.4yrs., 45.4% women). Multivariate covariance-based analyses of magnetic resonance imaging data, adjusted for potential confounders including single-task gait speed, were performed to identify gray matter patterns associated with dual-task gait speed. There were no differences in gait speed or cognitive performance during dual-task gait between individuals with non-amnestic mild cognitive impairment and amnestic mild cognitive impairment. Overall, increased dual-task gait speed was associated with a gray matter pattern of increased volume in medial frontal gyrus, superior frontal gyrus, anterior cingulate, cingulate, precuneus, fusiform gyrus, middle occipital gyrus, inferior temporal gyrus and middle temporal gyrus. The relationship between dual-task gait speed and brain substrates also differed by mild cognitive impairment subtype. Our study revealed a pattern of gray matter regions associated with dual-task performance. Although dual-task gait performance was similar in amnestic and non-amnestic mild cognitive impairment, the gray matter patterns associated with dual-task gait performance differed by mild cognitive impairment subtype. These findings suggest that the brain substrates supporting dual-task gait performance in amnestic and non-amnestic subtypes are different, and consequently may respond differently to interventions, or require different interventions.

How frequent and how clinically important are mood and behavioral symptoms among older adults with mild cognitive impairment (MCI)? Although these noncognitive behavioral symptoms (NCBS) are not represented in the diagnostic criteria for MCI, their clinical significance is increasingly recognized. To address this question, the authors identified a cohort of consecutively evaluated patients from a psychiatric hospital's outpatient memory clinic. These patients' records contained both a clinical assessment and a standardized set of evaluations including the Mini-Mental State Exam, the Neuropsychiatric Inventory (NPI), and the Geriatric Depression Scale. Using a standardized chart-review approach, the presence of any NPI-screened symptom was identified and the frequencies of specific NPI-screened symptoms were calculated for the Memory Clinic MCI cohort and for amnestic and non-amnestic MCI subgroups. A total of 116 patient records were reviewed. Thirty-eight patients with MCI were identified. Twenty-two of these met criteria for amnestic MCI by Mayo Clinic criteria while 16 met criteria for non-amnestic MCI. At least one NPI-screened mood or behavioral symptom was present in 86.8% of these MCI patients. Depression/dysphoria (63.3%), apathy (60.5%), anxiety (47.4%), irritability (44.7%), and nighttime behaviors (42.1%) were the most frequent. While depression/dysphoria was distributed similarly between amnestic and non-amnestic subgroups, apathy was significantly more frequently associated with the amnestic subtype of MCI, and nighttime behaviors were more frequently associated with the non-amnestic subtype. Although the presence of NCBS is not required for a diagnosis of MCI, these symptoms are frequently present and constitute an important source of morbidity. Apathy and depression may be difficult to differentiate, but targeted treatment of depression may fail to address apathy. Recognizing the limitations of this preliminary study, the authors suggest that apathy may be more characteristic of amnestic MCI while nighttime behaviors may be more characteristic of non-amnestic MCI.

BackgroundThe prevalence of mild cognitive impairment (MCI) is 14 to 18%. MCI has been associated with cardiovascular risk factors. Likewise, the APOEε4 genotype is a gene that confers susceptibility to Alzheimer’s disease. However, the association between APOE genotype, cardiovascular risk and MCI in the Mexican population is not clear, probably as a result of genetic heterogeneity.MethodWe included patients from memory clinic (INCMNSZ) from 2017 to 2019, &gt; 70 years. Three groups were studied: controls without cognitive impairment, with amnestic and nonamnestic MCI. Parametric and nonparametric statistics (x2, ANOVA, multivariate logistic regression analysis, Kruskal‐Wallis) were used for the analysis of statistical differences between groups.Result131 patients were studied, 67.9% were women, the average age was 73.6 (SD 7.3) and the educational level was 12.62 (SD 4.98). Regarding the APOE genotype, 93 (71%) were e3 / e3, 35 (26.7%) e3 / e4, 3 (2.3%) e4 / e4. Three groups of cognitive function were formed: cognitively healthy controls: 59 (45%), amnestic MCI: 29 (22.1%) and nonamnestic MCI: 42 (32.1%). In the group with nonamnestic MCI, statistically significant differences were found in dyslipidemia 48% (P = 0.014), history of CVD 16.5% (P = 0.033) and anemia 8% (0.034). For the group with amnestic MCI, 44.4% hypothyroidism was found (p = 0.15). The multivariate logistic regression analysis showed that the APOE genotype did not significantly modify the association with cardiovascular risk factors and MCI. A greater effect on motor executive function was found in the group of carriers of the APOEε4 genotype (p = 0.042)ConclusionOur study found a low frequency of APOE ε4, compared to African or European populations (Pygmy population, khoisan, waiwai) where the frequency is high (possibly related to race). Previous studies have shown an association between cardiovascular risk and cognitive risk in patients with APOE ε4, however, our study does not show an association between the state of APOE and risk for cognitive impairment, possibly related to variability genetics of the Mexican population, as well as the existence of possible polymorphisms not described in this population. Few studies have shown the association between APOE ε4 polymorphism, hypothyroidism and amnestic DCL.

The Value of Cognitive Screening Tests in Patients with Amnestic and Non-amnestic MCI.

Regional cortical atrophy in depression and neurocognitive disorders.

Olfactory impairment might be an important clinical marker and predictor of Alzheimer's disease (AD). In the present study, we aimed to compare the degree of olfactory identification impairment in each mild cognitive impairment (MCI) subtype, subjective memory impairment, and early AD dementia and assessed the relationship between olfactory identification and cognitive performance. We consecutively included 50 patients with amnestic MCI, 28 patients with non-amnestic MCI, 20 patients with mild AD, and 17 patients with subjective memory impairment (SMI). All patients underwent clinical and neuropsychological assessments. A multiple choice olfactory identification cross-cultural smell identification test was also utilized. Controlling for age and gender, olfactory impairment was significantly more severe in patients with AD and amnestic MCI compared with the results from the non-amnestic MCI and SMI groups. Higher scores on MMSE, verbal and non-verbal memory, and frontal executive function tests were significantly related to olfactory identification ability. In conclusion, olfactory identification is impaired in amnestic MCI and AD. These findings are consistent with previous studies. In amnestic MCI patients, this dysfunction is considered to be caused by underlying AD pathology.

Objective:While loss of insight into one’s cognitive impairment (anosognosia) is a feature in Alzheimer’s disease dementia, less is known about memory self-awareness in cognitively unimpaired (CU) older adults or mild cognitive impairment (MCI) or factors that may impact self-awareness. Locus of control, specifically external locus of control, has been linked to worse cognitive/health outcomes, though little work has examined locus of control as it relates to self-awareness of memory functioning or across cognitive impairment status. Therefore, we examined associations between locus of control and memory self-awareness and whether MCI status impacted these associations.Participants and Methods:Participants from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (mean age=73.51; 76% women; 26% Black/African American) were classified as CU (n=2177) or MCI (amnestic n=313; non-amnestic n=170) using Neuropsychological Criteria. A memory composite score measured objective memory performance and the Memory Functioning Questionnaire measured subjective memory. Memory self-awareness was defined as objective memory minus subjective memory, with positive values indicating overreporting of memory difficulties relative to actual performance (hypernosognosia) and negative values indicating underreporting (hyponosognosia). Internal (i.e., personal skills/attributes dictate life events) and external (i.e., environment/others dictate life events) locus of control scores came from the Personality in Intellectual Aging Contexts Inventory. General linear models, adjusting for age, education, sex/gender, depressive symptoms, general health, and vocabulary examined the effects of internal and external locus of control on memory self-awareness and whether MCI status moderated these associations.Results:Amnestic and non-amnestic MCI participants reported lower internal and higher external locus of control than CU participants. There was a main effect of MCI status on memory self-awareness such that amnestic MCI participants showed the greatest degree of hyponosognosia/underreporting, followed by non-amnestic MCI, and CU participants slightly overreported their memory difficulties. While, on average, participants were fairly accurate at reporting their degree of memory difficulty, internal locus of control was negatively associated with self-awareness such that higher internal locus of control was associated with greater underreporting (ß=-.127, 95% CI [-.164, -.089], p&lt;.001). MCI status did not moderate this association. External locus of control was positively associated with self-awareness such that higher external locus of control was associated with greater hypernosonosia/overreporting (ß=.259, 95% CI [.218, .300], p&lt;.001). Relative to CU, amnestic, but not non-amnestic, MCI showed a stronger association between external locus of control and memory self-awareness. Specifically, higher external locus of control was associated with less underreporting of cognitive difficulties in amnestic MCI (ß=.107, 95% CI [.006, .208], p=.038).Conclusions:In CU participants, higher external locus of control was associated with greater hypernosognosia/overreporting. In amnestic MCI, the lower external locus of control associations with greater underreporting of objective cognitive difficulties suggests that perhaps reduced insight in some people with MCI may result in not realizing the need for external supports, and therefore not asking for help from others. Alternatively, in amnestic participants with greater external locus of control, perhaps the environmental cues/feedback translate to greater accuracy in their memory self-perceptions. Longitudinal analyses are needed to determine how memory self-awareness is related to future cognitive declines.

A performance-prediction paradigm was used to examine metamemory abilities in 27 individuals with amnestic mild cognitive impairment (MCI), 14 individuals with nonamnestic MCI, and 41 controls. To assess memory self-awareness, participants predicted the number of words they would remember before completing a list-learning memory task. Memory self-monitoring was evaluated by participants' ability to increase the accuracy of their predictions after experience with the list-learning task. As expected, participants with amnestic MCI demonstrated poorer memory abilities than the controls and participants with nonamnestic MCI. The amnestic MCI group also correctly predicted that they would recall less information than controls. Furthermore, both MCI groups showed accurate awareness of how differing task demands influence recall and successfully modified their memory predictions to be more accurate following task exposure. These findings revealed that individuals with amnestic and nonamnestic MCI were able to competently assess the demands of an externally driven metamemorial situation and utilize experience with a task to accurately update memory self-knowledge. Accurate metamemory skills may facilitate the ability of individuals with MCI to benefit from targeted behavioral interventions focused on utilizing compensatory strategies for everyday memory problems.

The Association Between Decline in Physical Functioning and Atrophy of Medial Temporal Areas in Community-Dwelling Older Adults With Amnestic and Nonamnestic Mild Cognitive Impairment

The Patterns of Cognitive and Functional Impairment in Amnestic and Non-amnestic Mild Cognitive Impairment in Geriatric Depression

Discriminability of Mild Cognitive Impairment Subtypes Based on Neuropsychological Test Outcomes from a Memory Clinic in Puerto Rico

The aim of this study was to evaluate the reliability and validity of A Quick Test of Cognitive Speed (AQT) for detecting early-stage dementia in the elderly Japanese population. A total of 280 clinical participants (180 with mild Alzheimer's disease, 43 with amnestic mild cognitive impairment, 32 with non-amnestic mild cognitive impairment and 25 control subjects) and 22 community-dwelling elderly individuals without dementia were recruited. The Clinical Dementia Rating, the Mini-Mental State Examination, and AQT were administered to all participants. The Neurobehavioral Cognitive Status Examination was also administered to clinical participants. The intraclass correlation coefficient for the test-retest reliability of colour-form naming time on AQT was 0.88 (95% CI, 0.74-0.95, P < 0.001). AQT colour-form naming time was significantly correlated with the Clinical Dementia Rating, the total score on the Mini-Mental State Examination, and the total score on the Neurobehavioral Cognitive Status Examination and most of its subscales. AQT colour-form naming time was significantly longer in elderly individuals with mild Alzheimer's disease, amnestic mild cognitive impairment, and non-amnestic mild cognitive impairment than in control subjects. The receiver operating characteristic curve analysis indicated that AQT colour-form naming time significantly distinguished subjects with early-stage dementia (mild Alzheimer's disease, amnestic mild cognitive impairment, and non-amnestic mild cognitive impairment) from controls. The area under the curve was estimated to be 0.88 (95%CI = 0.82-0.95). A cut-off of 71/72 seconds yielded the best sensitivity/specificity trade-off: sensitivity = 85% and specificity = 76%. AQT is a useful brief screening tool for detecting early-stage dementia in elderly Japanese individuals.