Validation of the Thai version of the short Boston Naming Test (T-BNT) in patients with Alzheimer's dementia and mild cognitive impairment: clinical and biomarker correlates.

OBJECTIVES: Impairments in the Boston Naming Test (BNT), which measures confrontational word retrieval, frequently accompanies Alzheimer's dementia (AD) and may predict a more rapid progression of illness. This study aims to validate the Thai version of the 15-item BNT (T-BNT) in participants with AD and amnestic mild cognitive impairment (aMCI) and to externally validate the T-BNT using clinical and biomarker measurements. METHODS: This cross-sectional study recruited patients with AD, diagnosed according to NINCDS-ADRDA criteria (n = 60), aMCI, diagnosed using the Petersen criteria (n = 60), and healthy controls (n = 62). We examined the internal consistency, concurrent and discriminant reliability of the T-BNT. We also assessed the Mini Mental State Examination (MMSE), the Verbal Fluency Test (VFT) and the Word List Memory (WLM) tests and measured apolipoprotein E polymorphism and serum levels of folic acid, high-density lipoprotein cholesterol (HDL) and triglycerides. RESULTS: This study validated a 10-item T-BNT (10T-BNT), which yielded good internal consistency (0.92), a one-factor unidimensional structure, and adequate concurrent and discriminant validity. Lower scores on the 10T-BNT highly significantly predict AD, but not aMCI, and are positively associated with VFT and WLM test scores. Furthermore, lowered 10T-BNT scores are significantly associated with the ApoE4 allele, lower folate levels and an increased triglyceride/HDL-cholesterol ratio. CONCLUSIONS: This study validated the 10T-BNT and the total score on this scale is strongly associated with AD, impairments in semantic and episodic memory and biomarkers, which are known to modify memory via different mechanisms.

Pharmacological treatments for alleviating agitation in dementia: a systematic review and network meta-analysis.

AIMS: To determine the most efficacious and acceptable treatments of agitation in dementia. METHODS: MEDLINE, EMBASE, PsycINFO, CENTRAL and clinicaltrials.gov were searched up to 7 February 2017. Two independent reviewers selected randomized controlled trials (RCTs) of treatments to alleviate agitation in people with all-types dementia. Data were extracted using standardized forms and study quality was assessed using the revised Cochrane Risk of Bias Tool for RCTs. Data were pooled using meta-analysis. The primary outcome, efficacy, was 8-week response rates defined as a 50% reduction in baseline agitation score. The secondary outcome was treatment acceptability defined as treatment continuation for 8 weeks. RESULTS: Thirty-six RCTs comprising 5585 participants (30.9% male; mean ± standard deviation age, 81.8 ± 4.9 years) were included. Dextromethorphan/quinidine [odds ratio (OR) 3.04; 95% confidence interval (CI), 1.63-5.66], risperidone (OR 1.96; 95% CI, 1.49-2.59) and selective serotonin reuptake inhibitors as a class (OR 1.61; 95% CI, 1.02-2.53) were found to be significantly more efficacious than placebo. Haloperidol appeared less efficacious than nearly all comparators. Most treatments had noninferior treatment continuation compared to placebo, except oxcarbazepine, which was inferior. Findings were supported by subgroup and sensitivity analyses. CONCLUSIONS: Risperidone, serotonin reuptake inhibitors as a class and dextromethorphan/quinidine demonstrated evidence of efficacy for agitation in dementia, although findings for dextromethorphan/quinidine were based on a single RCT. Our findings do not support prescribing haloperidol due to lack of efficacy, or oxcarbazepine due to lack of acceptability. The decision to prescribe should be based on comprehensive consideration of the benefits and risks, including those not evaluated in this meta-analysis.

Characteristics of Mild Cognitive Impairment Using the Thai Version of the Consortium to Establish a Registry for Alzheimer's Disease Tests: A Multivariate and Machine Learning Study.

BACKGROUND: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) developed a neuropsychological battery (CERAD-NP) to screen patients with Alzheimer's dementia. Mild cognitive impairment (MCI) has received attention as a pre-dementia stage. OBJECTIVES: To delineate the CERAD-NP features of MCI and their clinical utility to externally validate MCI diagnosis. METHODS: The study included 60 patients with MCI, diagnosed using the Clinical Dementia Rating, and 63 normal controls. Data were analysed employing receiver operating characteristic analysis, Linear Support Vector Machine, Random Forest, Adaptive Boosting, Neural Network models, and t-distributed stochastic neighbour embedding (t-SNE). RESULTS: MCI patients were best discriminated from normal controls using a combination of Wordlist Recall, Wordlist Memory, and Verbal Fluency Test. Machine learning showed that the CERAD features learned from MCI patients and controls were not strongly predictive of the diagnosis (maximal cross-validation 77.2%), whilst t-SNE showed that there is a considerable overlap between MCI and controls. CONCLUSIONS: The most important features of the CERAD-NP differentiating MCI from normal controls indicate impairments in episodic and semantic memory and recall. While these features significantly discriminate MCI patients from normal controls, the tests are not predictive of MCI.

Early prediction of donepezil cognitive response in Alzheimer's disease by brain perfusion single photon emission tomography.

Currently, there is no effective means to evaluate donepezil response. We evaluated brain perfusion change at 4 h after donepezil administration (4 h DNPZ) to predict cognitive responses after 6 months of medication. CERAD neuropsychological assessment battery was used to define cognitive response at 6 months. We compared 4 h DNPZ to baseline single photon emission tomography (SPECT) by statistical parametric mapping to identify perfusion changes in responders (N = 16) and non-responders (N = 7). In responders, there were significant relatively increase in perfusion in left parietal lobe (BA39, 7, 1), right superior frontal gyrus (BA6) and right middle occipital gyrus (BA39). In the non-responders, perfusion was relatively increase in the left parietal lobe (BA39) only. In an explorative analysis, we found a significant correlation between perfusion changes in right BA6 and CERAD score changes at 6 months. Different SPECT perfusion changes at 4 h after donepezil administration were demonstrated in the group of responders and non-responders with potential correlation with CERAD score change. Thus, 4 h DNPZ brain perfusion SPECT can be used to predict donepezil response at 6 months.

Peripheral Blood Biomarkers Coupled with the Apolipoprotein E4 Genotype Are Strongly Associated with Semantic and Episodic Memory Impairments in Elderly Subjects with Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: The Apolipoprotein E4 (ApoE4) genotype is strongly associated with Alzheimer's disease (AD), although the presence of the ApoE4 allele alone is not sufficient to explain AD. The pathophysiology of amnestic mild cognitive impairment (aMCI) remains unclear. OBJECTIVE: This study aims to examine associations between peripheral blood biomarkers coupled with ApoE4 and episodic and semantic memory. METHODS: The CERAD battery was completed and various biomarkers were assayed in 60 subjects with aMCI, 60 with AD, and 62 healthy controls. RESULTS: Deficits in semantic and episodic memory were significantly predicted by anion gap and bicarbonate, albumin, and glucose coupled with ApoE4. Furthermore, these peripheral biomarkers interacted with ApoE to predict greater memory impairments. CONCLUSIONS: Peripheral blood biomarkers may interact with pathways related to ApoE4 to predict greater semantic and episodic memory impairments, thus contributing to the pathophysiology of aMCI and AD. Our data suggest that the transition from aMCI to AD could at least in some cases be associated with significant interactions between ApoE4 and those peripheral blood biomarkers.

Auditory symptoms: a critical clue for diagnosis of MELAS.

Mitochondrial encephalopathy, lactic acidosis with stroke-like episodes (MELAS) is a rare mitochondrial disorder that affects adults. MELAS syndrome can mimic cerebrovascular disease, encephalitis or toxic-metabolic encephalopathy. The authors reported two patients who presented with auditory symptoms before the onset of encephalopathy and stroke-like episodes. The first patient was a 28 year-old man, who presented with acute sensorineural hearing loss (SNHL) followed by headache, left hemiparesis and generalized tonic-clonic seizure. CT scan of the brain showed hypodensity lesion at the tip of right temporooccipital region. Audiogram and brainstem auditory evoked potential (BAEP) showed abnormal conduction of left brainstem auditory pathway. MRI of the brain showed a lesion involving gray and white matters of the right occipital, parietal and temporal lobes. The distribution of the lesions was not compatible with distribution of arterial supply. MRA was normal. The second patient was a 56 year-old woman with a one-year history of hearing loss. The audiogram revealed bilateral SNHL. A few days before admission, her hearing was acutely deteriorated She could not understand a conversation while she could communicate by writing. CT scan of the brain showed hypodensity in both temporal lobes and MRI revealed lesions in the same area. Pure tone audiogram showed moderate SNHL but BAEP was normal. One week later, she developed global dysphasia and generalized tonic-clonic seizure. Both patients had elevated cerebrospinal fluid and serum lactate: pyruvate ratio. Polymerase chain reaction-restriction fragment length polymorphism disclosed A3243G mtDNA mutation in the blood in the first patient and in muscle biopsy in the second patient. Ubiquinone supplement was prescribed The auditory symptoms in combination with stroke-like episode in supratentorium are important clues to diagnose MELAS syndrome.

Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers.

OBJECTIVE: In this prospective cohort study, we investigated cerebral glucose metabolism reductions on [(18)F]-fluorodeoxyglucose (FDG)-PET in progranulin (GRN) mutation carriers prior to frontotemporal dementia (FTD) onset. METHODS: Nine mutation carriers (age 51.5 ± 13.5 years) and 11 noncarriers (age 52.7 ± 9.5 years) from 5 families with FTD due to GRN mutations underwent brain scanning with FDG-PET and MRI and clinical evaluation. Normalized FDG uptake values were calculated with reference to the pons. PET images were analyzed with regions of interest (ROI) and statistical parametric mapping (SPM) approaches. RESULTS: Compared with noncarriers, GRN mutation carriers had a lowered anterior-to-posterior (AP) ratio of FDG uptake (0.86 ± 0.09 vs 0.92 ± 0.05) and less left-right asymmetry, consistent with an overall pattern of right anterior cerebral hypometabolism. This pattern was observed regardless of whether they were deemed clinically symptomatic no dementia or asymptomatic. Individual ROIs with lowered FDG uptake included right anterior cingulate, insula, and gyrus rectus. SPM analysis supported and extended these findings, demonstrating abnormalities in the right and left medial frontal regions, right insular cortex, right precentral and middle frontal gyri, and right cerebellum. Right AP ratio was correlated with cognitive and clinical scores (modified Mini-Mental State Examination r = 0.74; Functional Rating Scale r = -0.73) but not age and years to estimated onset in mutation carriers. CONCLUSION: The frontotemporal lobar degenerative process associated with GRN mutations appears to begin many years prior to the average age at FTD onset (late 50s-early 60s). Right medial and ventral frontal cortex and insula may be affected in this process but the specific regional patterns associated with specific clinical variants remain to be elucidated.