Amnestic Type Research Articles

The role of arterial, venous blood and cerebrospinal fluid flow disturbances in forming cognitive impairment types in age-related cerebral microangiophathy

Age-related cerebral microangiopathy (small vessel disease, SVD) is the main cause of vascular and mixed cognitive impairment (CI) with a complex neuropsychological profile. To investigate the role of arterial and venous blood flow and cerebrospinal fluid (CSF) flow, as well as their interrelation, in the forming of CI types in patients with SVD. Fifty patients (31 f., mean age 61.2±6,2) with SVD (STRIVE, 2013), including 37 with mild CI and 13 with dementia, were examined. A type of CI was determined based on combination of standard deviations from normal results on memory and executive function tests: isolated dysexecutive (13) and predominantly dysexecutive (6), predominantly amnestic (12), mixed, equal impairment of EF and memory, (19). In the statistical analysis, groups of the isolated and predominantly dysexecutive types were merged according to the dominance of deviations in the EF into the dysexecutive type of CI (19). Phase contrast MRI (PhC-MRI) was used to assess characteristics of arterial and venous blood flow and CSF flow on different levels. Indexes of pulse and intracranial compliance and surface of the cerebral aqueduct were calculated. Patients with all CI types had a CSF flow systolic peak delay at the cervical level. Mixed and dysexecutive CI types as compared with predominantly amnestic type and control were defined by blood flow reduction in the sinus rectus, and mixed type by the additional decrease in its pulse wave width, blood flow reduction in an internal jugular artery and maximal blood flow velocity in the inner carotid artery, the increase in the intracranial compliance index and surface of the cerebral aqueduct. The neuropsychological CI type in SVD is defined by features of pathophysiological mechanisms conditioned on differences in blood flow and CSF flow impairment severity and formed hydrodynamic interaction between them. Differential features of CI types in SVD defined by PhC-MRI might become important predictive indicators of potential interaction between SVD and degeneration, improve understanding of risk factors, pathogenesis, prevention and treatment of age-related brain damage.

Studies of the Efficacy of Cereton in Mild Cognitive Impairment of the Amnestic Type Based on Testing Lipid Markers

Studies of the Efficacy of Cereton in Mild Cognitive Impairment of the Amnestic Type Based on Testing Lipid Markers

Intrinsic neurocognitive network connectivity differences between normal aging and mild cognitive impairment are associated with cognitive status and age.

Mild cognitive impairment (MCI) of the amnestic type is considered to be a transitionary stage between healthy aging and Alzheimer's disease (AD). Previous studies have demonstrated that intrinsic functional connectivity of the default network (DN) is altered in normal aging and AD and impacts both within- and between-network connectivity. Although changes within the DN have been reported in MCI, it remains uncertain how interactions with other large-scale brain networks are altered in this prodromal stage of AD. We investigated within- and between-network connectivity in healthy older adults (HOAs) and older adults with MCI across 3 canonical brain networks: DN, dorsal attention network, and frontoparietal control network. We also assessed how patterns of functional connectivity among the 3 networks predicted cognitive status and age using multivariate partial least squares. A total of 91 MCI and 71 HOA resting-state scans were analyzed from the Alzheimer's Disease Neuroimaging Initiative. There were 3 key findings. First, a circumscribed pattern of greater between-network and interhemispheric connectivity was associated with higher cognitive status in HOAs. Second, for individuals with MCI, cognitive status was positively associated with a more distributed, less-differentiated pattern of intrinsic functional connectivity across the 3 networks. Finally, greater within-network functional connectivity was positively associated with cognitive status for HOAs irrespective of age; however, this compensation-like effect diminished with increasing age for participants with MCI. Although reliable differences between healthy aging and MCI in the intrinsic network architecture of the brain are apparent, these differences emerge as shifting associations between network interactivity, cognitive functioning, and age.

Cognitive Blackouts in Mild Cognitive Impairment and Alzheimer’s Dementia

Background: Cognitive blackouts, e.g. moments of amnesia, disorientation, or perplexity may be an early sign of incipient Alzheimer’s dementia (AD). A short questionnaire, the checklist for cognitive blackouts (CCB), was evaluated cross-sectionally in users of a memory clinic. Methods: The CCB was performed in 130 subjects, who further underwent a neuropsychological and clinical examination. Subjective memory impairment and depressive symptoms were assessed. Differences in the CCB score between diagnostic groups and relationships with cognitive performance, depression, and subjective memory impairment were analyzed. Results: The CCB score was increased in mild cognitive impairment of the amnestic type or mild AD and correctly predicted 69.2% of the respective subjects. It was negatively correlated with cognitive performance, positively correlated with depressive symptoms, and substantially increased in subjects who estimated their memory poorer than that of other persons of their age. Discussion: The CCB may be a helpful screening tool for the early recognition of AD.

The use of cluster analysis and logistic regression for assessing the risk of Alzheimer's disease in patients with mild cognitive impairment, amnestic type

The evaluation of the risk of Alzheimer disease (AD) in patients with cognitive impairment, amnestic type (aMCI) on the basis of cluster analysis and logistic regression with the use of such markers of inflammation as enzymatic activity of leukocyte elastase (LE) and the functional activity of α1-proteinase inhibitor (α1-PI). The study object of statistical analysis was the database, including the results of LE activity and functional α1-PI activity in blood plasma of 78 outpatients with aMCI (25 men and 53 women, aged 44 to 89 years (69.1±9.95). Clustering by k-means and classification by logistic regression indicate a high probability of AD in patients with aMCI depending on the activity of LE and α1-PI in blood plasma. The total coincidence of objects included in the clusters and in the AD risk group was 94%. The high coincidence of two different methods of grouping confirms the previously stated notion of the possibility of identifying patients with the high risk of AD among patients with aMCI by the activity of LE and α1-PI in the blood.

Repetitive Questioning Exasperates Caregivers.

Repetitive questioning is due to an impaired episodic memory and is a frequent, often presenting, problem in patients with Alzheimer’s disease (amnestic type). It is due to the patients’ difficulties learning new information, retaining it, and recalling it, and is often aggravated by a poor attention span and easy distractibility. A number of factors may trigger and maintain repetitive questioning. Caregivers should try to identify and address these triggers. In the case discussion presented, it is due to the patient’s concerns about her and her family’s safety triggered by watching a particularly violent movie aired on TV. What went wrong in the patient/caregiver interaction and how it could have been avoided or averted are explored. Also reviewed are the impact of repetitive questioning, the challenges it raises for caregivers, and some effective intervention strategies that may be useful to diffuse the angst that caregivers experience with repetitive questioning.

Clinical efficacy and safety of choline alfoscerate in the treatment of late-onset cognitive impairment

To study the efficacy and safety of cereton (choline alfoscerate) in the treatment of elderly patients with amnestic type of mild cognitive impairment (aMCI), which often represents a pre-dementia (symptomatic) stage of Alzheimer's disease (AD). Fifty patients (40 women and 10 men; mean age 68,8 years) received three-month therapy with cereton in a dose of 1200 mg/day in 3 divided doses. Fifteen patients received the same treatment again within 1 year. Immediate and delayed (7-9 months after treatment) effects of therapy, including those dependent on the ApoE genotype were assessed with a neuropsychological test battery. Psychometric measures showed a significant improvement after treatment with cereton. ApoE4 allele noncarriers performed better on tests of immediate and delayed reproduction of 10 words. Although, most indicators achieved in the end of therapy course decreased 7-9 months after treatment, the level of patients cognitive functioning remained at a higher level than before treatment. A repeated course of cereton treatment prevents cognitive deficit increasing during the follow-up period (10-12 months). The drug is well-tolerated and safe and can be recommended for preventive treatment of dementia in patients with high AD risk, in particular in elderly patients with aMCI syndrome.

Effects of Combined Physical and Cognitive Exercises on Cognition and Mobility in Patients With Mild Cognitive Impairment: A Randomized Clinical Trial

ImportanceAlthough participation in physical and cognitive activities is encouraged to reduce the risk of dementia, the preventive efficacy of these activities for patients with mild cognitive impairment is unestablished. ObjectiveTo compare the cognitive and mobility effects of a 40-week program of combined cognitive and physical activity with those of a health education program. DesignA randomized, parallel, single-blind controlled trial. SettingA population-based study of participants recruited from Obu, a residential suburb of Nagoya, Japan. ParticipantsBetween August 2011 and February 2012, we evaluated 945 adults 65 years or older with mild cognitive impairment, enrolled 308, and randomly assigned them to the combined activity group (n = 154) or the health education control group (n = 154). InterventionsThe combined activity program involved weekly 90-minute sessions for 40 weeks focused on physical and cognitive activities. The control group attended 90-minute health promotion classes thrice during the 40-week trial period. MeasurementThe outcome measures were assessed at the study's beginning and end by personnel blinded to mild cognitive impairment subtype and group. The primary endpoints were postintervention changes in scores on (1) the Mini-Mental State Examination as a measure of general cognitive status and memory, (2) the Wechsler Memory Scale-Revised–Logical Memory II, and (3) the Rey Auditory Verbal Learning Test. We applied mobility assessments and assessed brain atrophy with magnetic resonance imaging. ResultsCompared with the control group, the combined activity group showed significantly greater scores on the Mini-Mental State Examination (difference = 0.8 points, P = .012) and Wechsler Memory Scale-Revised–Logical Memory II (difference = 1.0, P = .004), significant improvements in mobility and the nonmemory domains and reduced left medial temporal lobe atrophy in amnestic mild cognitive impairment (Z-score difference = −31.3, P < .05). ConclusionCombined physical and cognitive activity improves or maintains cognitive and physical performance in older adults with mild cognitive impairment, especially the amnestic type.

Clinical and neuropsychological profile of persons with mild cognitive impairment, a hospital based study from a lower and middle income country.

Mild Cognitive impairment (MCI) is an important pre-dementia stage to be identified towards prevention. We screened a large number of older adults seeking help at hospital and community towards a diagnosis of MCI and this study describe their clinical and neuropsychological profile. Older adults aged 60 years & above seeking help at NIMHANS outpatient & community services were screened for early cognitive deficits. Persons were diagnosed to have MCI according to Petersen's criteria, after detailed clinical and neuropsychological assessments. Age, gender and education matched healthy controls were recruited for comparison. A total of 7469 older adults were screened during the study period (July 2012-December 2014). Less than 1% (n=56) were diagnosed with MCI. Majority were males, from urban background with an average of 13 years of education. They presented mainly with memory disturbances, more than 75% (n=43) were found to have amnestic type of MCI (aMCI). Of the aMCI subjects, majority (80%) had deficits in more than one cognitive domain. They performed significantly worse (p<0.001) on tests of episodic memory, logical memory, attention and executive functions. Neuropsychiatric symptoms were prevalent in 55% of MCI group and influenced their cognitive scores. The findings suggest that persons with MCI perform worse not only on memory tasks but also on some of the attention and executive functions tasks. As observed in earlier studies, amnestic multiple-domain MCI was the most common type of MCI in this study population. Indigenous assessment tools were of significant value in distinguishing MCI from normal ageing.

NEW ANALYSES OF LANGUAGE PROCESSING REVEAL THAT SEMANTICS DISSOCIATES FROM SYNTAX IN MILD COGNITIVE IMPAIRMENT

Semantic memory deficits are evident in MCI. While recent evidence has also shown subtle differences in more complex language production there is little evidence on the mechanisms by which semantics and syntax interact in MCI. In this inter-institutional research, we evaluated the roles of semantics and syntax in MCI, amnestic type (n=21, aged 68–88)) and Healthy Aging (n=25, aged 62–87). Subjects were presented with an Elicited Imitation test, in which they repeated 60 sentences including Relative clauses (RC), Coordinate (CS) and Adverbial subordinate (ASC) sentences. Sentences were controlled for length and lexical frequency and varied by semantic plausibility with half semantically implausible. Subjects were also administered the Addenbrook's Cognitive Estimation Test-Revised (ACE-R) which provides a total score and scores within different cognitive domains. For both groups, there was a significant difference in elicited imitation success favoring semantically plausible sentences, and no significant interaction between semantics and group. Although MCI subjects were significantly less accurate in imitating sentences relative to HA for all sentences types (RC: HA > MCI (p=0.0012, t=3.35); CS: HA > MCI (p=0.0077, t=2.71); ASC: HA > MCI (p=0.0052, t=2.86)), both groups showed the same pattern of sentence success across both semantic conditions. Regression tests of cognitive variables against linguistic performance suggested a significant predictive effect of cognition in HA, but not MCI. Analysis of ACE-R components revealed that phonemic, but not semantic fluency significantly predicted linguistic success in both groups. Findings suggest that in MCI semantic and syntactic deficits are to some degree divorced. A more complete analysis of language is necessary to strengthen neuropsychological profiling in clinical MCI assessment. Findings suggest that a distinction of MCI from HA does not involve cognitive deficit in semantic memory alone. Given that MCI subjects were less successful on this task in both semantic conditions and that general cognition and semantic fluency do not predict sentence production, we suggest that the ability to integrate semantic memory with the syntactic computation necessary for language comprehension and production may explain our results.

INTERCORRELATIONS BETWEEN CSF AMYLOID BETA LEVELS AND NEUROPSYCHOLOGICAL PROFILES AMONG PARTICIPANTS WITH SUBJECTIVE COGNITIVE IMPAIRMENT AND MCI OF THE AMNESTIC TYPE

Clinical symptoms and pathophysiological process of Alzheimer's Disease (AD) could be conceptualized as a continuum or trajectory. While change in amyloid-β (Aβ) 1−42 concentration in cerebrospinal fluid, which is thought to be the earliest pathophysiological process of AD trajectory, the earliest and core symptom of typical AD is generally an impairment in episodic memory. These changes are specific and sensitive predictive factors for people converting from mild cognitive impairment (MCI) and subjective cognitive impairment (SCI) to AD dementia. The aim of this study is to investigate how CSF Aβ1−42 concentration is related to free and cued recall and other cognitive functions in MCI and SCI. Our sample included 18 amnestic type MCI patients and 19 individuals with SCI. All participants underwent a multisession study including lumbar puncture and neuropsychological assessment. We used Free and Cued Selective Reminding Test to evaluate free and cued recall performance. These data were taken from an ongoing large study. Initial findings revealed that, compared to SCI group, MCI patients had lower scores on both free recall and cue index (t= 7.803 and 4.480, p<.05). Both free and cued recall were correlated to different measures of executive functioning and language (naming) (r values ranged between .46 and .65, p<.05) within SCI and MCI groups. In addition, among participants with MCI, lower CSF Aβ concentration was significantly related to worse free recall performance (r=.67, p<.05). As expected, there was no relationship between performance of recalling from cues and Aβ concentration within this group. Preliminary results revealed a significant relationship between higher Aβ pathology and free recall impairment within MCI group. On the other hand, cued recall impairment, which is a hallmark feature of AD, was not associated with Aβ pathology. Neither of the memory scores correlated with amyloid concentration among participants with SCI. It might be the case that in the continuum of AD, memory performance first interacts with executive functioning and language, and later with Aβ pathology in the CSF before the decrease of Aβ1–42 reaches a plateau.

THE RELATIONSHIP BETWEEN CSF AMYLOID BETA CONCENTRATIONS AND FREE AND CUED RECALL PERFORMANCE AMONG PARTICIPANTS WITH AMNESTIC MILD COGNITIVE IMPAIRMENT

Alzheimer's Disease (AD) is a neurodegenerative disease which typically presents with a specific episodic memory impairment. Although accumulation of hypertphosphoryllated tau is held responsible for the neurodegeneration and hence the symptoms of AD, recent research suggests that changes in amyloid-β (Aβ) 1−42 concentrations might also be related to memory performance. We aimed to investigate whether cerebro-spinal fluid (CSF) Aβ42 concentrations are related to free and cued recall performance among a group of patients with amnestic type MCI. The results that will be presented here are part of a still ongoing research project. Currently, we have 18 participants diagnosed with amnestic type MCI. All participants underwent an extended procedure involving neurological examination, multimodal neuroimaging, neuropsychological assessment, and lumbar puncture for CSF biomarkers. Free and Cued Selective Reminding Test was used as the principal measure to assess memory performance. The CSF Aβ42 concentrations of the sample ranged between 299 and 1377 pg/mL. Based on their Aβ concentration, we assigned the sample into two groups: low Aβ group (n=9) and high Aβ group (n=9). The cutoff value was 850 pg/mL. Then, 2 groups were compared with regard to their FCSRT scores. Significant intergroup differences were found with regard to total free recall performance. Specifically, high-amyloid group had significantly higher total free recall scores than low amyloid group (U= 14.00, p<.05). On the other hand, with respect to cue index scores, which an indicator of how each participant is able to benefit from cues, there was not a statistically significant difference between the two groups. Our initial results suggest that reduced CSF Aβ42 concentrations might interfere with free recall performance. The fact that no significant relationship was found with regard to cued recall (which is a specific feature of AD amnesia) might suggest that Aβ42-related amnesia is different from tau-related one, which disconnects entorhinal cortex from the hippocampal formation initially and hence gives rise to typical amnesia (hippocampal-type) that does not improve with cuing. Functional disconnections due to Aβ42 accumulation within a larger network, such as default mode (DMN) is likely to underline such a non-hypocampal-type memory deficit.

Membrane characteristics and vascular cognitive impairment

Objective : to study the clinical phenomenology of vascular cognitive impairment (VCI) in individuals with different rates of passive transmembrane ion transport. Patients and methods. Cognitive functions were evaluated in 372 patients with different clinical variants of moderate VCI after 1, 5, and 10 years of follow-up. Quantile analysis was used to group patients into quartiles according to the ranges in the rate of passive transmembrane ion transport reflecting the genetically determined properties of cell membranes and identified by the study of Na+–Li+ countertransport (NLC) in the erythrocyte membrane. Results. There was initially a monofunctional non-amnestic type in 11.0% of the patients, a monofunctional amnestic type in 16.1%, a multifunctional non-amnestic type in 34.9%, and a multifunctional amnestic type in 37.9%. At the same type, in the patients with high-speed NLC, the number of amnestic VCI types statistically dominated: 77.1% of the patients belonging to IV quartile. After 1 year and 5 years of follow-up, there was an increase in the number of patients with severe cognitive impairment, reaching the degree of dementia (33.2% of all the examinees following 1 year). The patients with high-speed NLC showed a significant predominance of not only the total number of dementias (86.7% of the patients in IV quartile; p<0.001), but also a more unfavorable mixed (disregulatory + Alzheimer's disease) type of dementia (74.7% of the patients in IV quartile; p<0.001). The dysregulatory type of dementia was more common in patients with low- and moderate-speed NLC. 70% of all dementias formed from the multifunctional amnestic type of mild cognitive impairment (MCI). Different types of MCI were observed to be transformed to the prognostically unfavorable multifunctional amnestic type of MCI. The study conducted 10 years later noted the same trends. Conclusion. The NLC speed has been shown to be associated with the VCI profile, which makes this indicator promising for predicting the course of VCI in the early stage of the disease and for choosing a treatment policy.

Patients with Dementia Are Easily Distracted.

Mild cognitive impairment (MCI) is the middle ground between normal, age-appropriate memory impairment, and dementia. Whereas patients with MCI are able to cope with the memory deficit, those with dementia are not: Their memory impairment and other cognitive deficits are of sufficient magnitude to interfere with the patients’ ability to cope independently with daily activities. In both MCI and dementia, there is evidence of declining cognitive functions from a previously higher level of functioning. In both the conditions, there is also an evidence of dysfunction in one or more cognitive domains. There are two subtypes of MCI depending on whether memory is predominantly affected: amnestic type and nonamnestic/behavioral type. Not all patients with MCI transition to dementia, some recover. In this case scenario, we present a 68-year-old man with MCI who lives with his wife. They are getting ready to host dinner. His wife asks him to vacuum the dining room while she runs an urgent errand. We describe how this simple task vacuuming a room ended in a catastrophe with the patient spending the night in jail and his wife hospitalized. We discuss what went wrong in the patient/wife interaction and how the catastrophic ending could have been avoided.ObjectivesAt the end of this case discussion readers will know the following:The differences between mild cognitive impairment (MCI), normal aging, and dementia.MCI is often a precursor of dementia and has an amnestic or nonamnestic/behavioral presentation. However, not all patients with MCI develop dementia, some even recover.MCI is an opportunity to discuss with the patient various issues that may arise, should it progress to dementia such as preparing a will, transitioning from driver to passenger, and addressing various financial and legal issues including end-of-life issues and selecting someone to have power of attorney.Patients with MCI should be regularly followed up to determine whether and when they will transition to dementia as this changes the level of care needed.Patients with MCI are at an increased risk of triggering accidents because of their cognitive impairment and often impaired judgment.It may be hazardous to leave patients with MCI alone, without supervision.The importance of support groups, social media, and cameras when providing care to patients with MCI and dementias.

Systemic inflammatory markers in age-associated cognitive impairment and Alzheimer's disease

To determine a complex of immune markers reflecting various links of multicomponent inflammatory reactions in amnestic type of mild cognitive impairment (aMCI) in comparison with Alzheimer's disease (AD). Sixty-seven patients with aMCI, aged 72 [63; 77] years, and 91 patients with Alzheimer's disease at the age of 74 [68; 79] years were examined. The aMCI was diagnosed according to the criteria of R.S. Petersen et al. (1999) and B. Dubois et al. (2014). The diagnosis of AD was established in accordance with the ICD-10 and NINCDS-ADRDA criteria. The degree of dementia severity was determined by clinical signs using the CDR (Clinical Dementia Rating) and the Mini Mental State Examination (MMSE) total score. The control group included 38 age- and sex-matched individuals. Immune and biochemical parameters were determined in blood plasma. The activity of LE and α1-PI was determined by spectrophotometric method. Concentrations of IL-6 and CRP were measured by enzyme immunoassay. AD was characterized by the significant decrease in LE activity (p<0.0001) and increase in the activity/levels of α1-PI, CRP and IL-6 (p<0.001; p<0.05; p<0.01, respectively) compared to controls. CDR and MMSE scores were correlated with the LE activity (r=-0.38, r=0.31, p<0.05), i.e. cognitive decline was associated with decreased activity of LE. aMCI was characterized by the significant increase in the activity/level of α1-PI and IL-6 (p<0.0001; p<0.01). In 30% of patients with aMCI, a spectrum of inflammatory markers, typical for patients with AD, was determined. Based on the results of comparative analysis of aMCI and AD, one can suggest that one third of patients with aMCI represents a group of ultra-high risk of AD. These patients need a dynamic follow-up with a regular assessment of the state of cognitive functions and possibly preventive therapy.

Therapeutic monitoring and prediction of the efficacy of neurotrophic treatment in patients with amnestic type of mild cognitive impairment

To perform therapeutic monitoring and prediction of the neurotrophic therapy efficacy in patients with amnestic type of mild cognitive impairment (aMCI) in a model of course cerebrolysin therapy. The study involved a group of 19 elderly patients who met the diagnostic criteria of aMCI. All patients received a course of neurotrophic therapy consisting of 20 intravenous infusions of cerebrolysin (30 ml of cerebrolysin in 100 ml of isotonic sodium chloride solution). To assess the therapy efficacy, psychometric scales (CGI, MMSE, MoCA-test, МDRS, FAB, Clock Drawing Test, BNT, Word Recall test, delayed reproduction of 10 words, naming digits in a direct and reverse order) were used at 0, 4, 10 and 26 weeks of the study. Antibodies to p75 neurotrophin receptor (NTR) were measured by ELISA in blood serum of 19 patients before cerebrolysin therapy and after 10 and 26 weeks of treatment. The study showed that аMCI patients had an increased level of antibodies against P75NTR that was significantly decreased after 5.5 month of cerebrolysin treatment. Therefore, it can be a potential biomarker of long-term therapeutic effect of cerebrolysin treatment in aMCI patients. The modified fragment 155-164 of P75 NTR determined in the serum of patients can be an effective indicator for monitoring and predicting the efficacy of long-term neurotrophic therapy.

Cognitive performance of older adults in a specialized diabetes clinic.

Diabetes mellitus is a risk factor for cognitive changes, but assessment for cognitive disorders in this population is performed infrequently. The present study examined the frequency of cognitive disorders and patterns of deficit in patients enrolled in a specialized clinic for diabetes. A cross-sectional study was conducted to assess cognition in Mount Sinai Diabetes Center patients. Thirty eligible subjects aged ≥50 years were assessed and compared with non-diabetic cognitively normal control subjects, as well as non-diabetic subjects with mild cognitive impairment (MCI). The main outcome(s) and measure(s) were obtained through cognitive assessment and diagnosis using the Alzheimer's Disease Centers' uniform data set. Forty percent of subjects were newly diagnosed with a cognitive disorder: 10% were diagnosed with dementia and 30% with MCI. Diabetic subjects performed worse on the Mini-Mental State Examination (27.2 vs 28.4; P = 0.0132), list generation (9.5 vs 12.2; P = 0.0190), Trail Making Test, Parts A (70.1 vs 43.0; P < 0.0001) and B (197.2 vs 123.6; P < 0.0001), and the Digit Symbol test (12.7 vs 40.1; P < 0.0001) than cognitively normal individuals. Compared with subjects with MCI (amnestic type), diabetic subjects performed better on tasks of immediate and delayed recall (11.2 vs 7.3 [P = 0.0048] and 8.4 vs. 4.1 [P = 0.0003], respectively). Undiagnosed cognitive disorders are common and underappreciated in patients being treated in a specialized diabetes clinic. It may be important to make cognitive assessment a standard part of patient assessments.

Relative impact of amyloid-β, lacunes, and downstream imaging markers on cognitive trajectories.

SEE COHEN DOI101093/AWW183 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Amyloid-β and cerebral small vessel disease are the two major causes of cognitive impairment in the elderly. However, the underlying mechanisms responsible for precisely how amyloid-β and cerebral small vessel disease affect cognitive impairment remain unclear. We investigated the effects of amyloid-β and lacunes on downstream imaging markers including structural network and cortical thickness, further analysing their relative impact on cognitive trajectories. We prospectively recruited a pool of 117 mild cognitive impairment patients (45 amnestic type and 72 subcortical vascular type), from which 83 patients received annual follow-up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and 87 patients received a second Pittsburgh compound B positron emission tomography analysis. Structural networks based on diffusion tensor imaging and cortical thickness were analysed. We used linear mixed effect regression models to evaluate the effects of imaging markers on cognitive decline. Time-varying Pittsburgh compound B uptake was associated with temporoparietal thinning, which correlated with memory decline (verbal memory test, unstandardized β = -0.79, P < 0.001; visual memory test, unstandardized β = -2.84, P = 0.009). Time-varying lacune number was associated with the degree of frontoparietal network disruption or thinning, which further affected frontal-executive function decline (Digit span backward test, unstandardized β = -0.05, P = 0.002; Stroop colour test, unstandardized β = -0.94, P = 0.008). Of the multiple imaging markers analysed, Pittsburgh compound B uptake and the number of lacunes had the greatest association with memory decline and frontal-executive function decline, respectively: Time-varying Pittsburgh compound B uptake (standardized β = -0.25, P = 0.010) showed the strongest effect on visual memory test, followed by time-varying temporoparietal thickness (standardized β = 0.21, P = 0.010) and time-varying nodal efficiency (standardized β = 0.17, P = 0.024). Time-varying lacune number (standardized β = -0.25, P = 0.014) showed the strongest effect on time-varying digit span backward test followed by time-varying nodal efficiency (standardized β = 0.17, P = 0.021). Finally, time-varying lacune number (β = -0.22, P = 0.034) showed the strongest effect on time-varying Stroop colour test followed by time-varying frontal thickness (standardized β = 0.19, P = 0.026). Our multimodal imaging analyses suggest that cognitive trajectories related to amyloid-β and lacunes have distinct paths, and that amyloid-β or lacunes have greatest impact on cognitive decline. Our results provide rationale for the targeting of amyloid-β and lacunes in therapeutic strategies aimed at ameliorating cognitive decline.

Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia.

This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer’s disease. Twenty-nine patients with probable Alzheimer’s disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L) to subjective memory complaint (4.3±0.9 μmol/L), mild cognitive impairment (4.0±0.53 μmol/L), up to Alzheimer’s disease (3.5±0.6 μmol/L) group (p<0.001). The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer’s disease group; and subjective memory complaint vs. Alzheimer’s disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer’s disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer’s disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer’s disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal study is needed before application to clinical practice.

The Differentiation of Amnestic Type MCI from the Non-Amnestic Types by Structural MRI.

Introduction: While amnestic mild cognitive impairment (aMCI) and non-amnestic mild cognitive impairment (naMCI) are theoretically different entities, only a few investigations studied the structural brain differences between these subtypes of mild cognitive impairment. The aim of the study was to find the structural differences between aMCI and naMCI, and to replicate previous findings on the differentiation between aMCI and healthy controls.Methods: Altogether 62 aMCI, naMCI, and healthy control subjects were included into the study based on the Petersen criteria. All patients underwent a routine brain MR examination, and a detailed neuropsychological examination.Results: The sizes of the hippocampus, the entorhinal cortex and the amygdala were decreased in aMCI relative to naMCI and to controls. Furthermore the cortical thickness of the entorhinal cortex, the fusiform gyrus, the precuneus and the isthmus of the cingulate gyrus were significantly decreased in aMCI relative to naMCI and healthy controls. The largest differences relative to controls were detected for the volume of the hippocampus (18% decrease vs. controls) and the cortical thickness (20% decrease vs. controls) of the entorhinal cortex: 1.6 and 1.4 in terms of Cohen's d. Only the volume of the precuneus were decreased in the naMCI group (5% decrease) compared to the control subjects: 0.9 in terms of Cohen's d. Significant between group differences were also found in the neuropsychological test results: a decreased anterograde, retrograde memory, and category fluency performance was detected in the aMCI group relative to controls and naMCI subjects. Subjects with naMCI showed decreased letter fluency relative to controls, while both MCI groups showed decreased executive functioning relative to controls as measured by the Trail Making test part B. Memory performance in the aMCI group and in the entire sample correlated with the thickness of the entorhinal cortex and with the volume of the amygdala.Conclusion: The amnestic mild cognitive impairment/non-amnestic mild cognitive impairment separation is not only theoretical but backed by structural imaging methods and neuropsychological tests. A better knowledge of the MCI subtypes can help to predict the direction of progression and create targeted prevention.