An elderly patient with Alzheimer’s disease,normal pressure hydrocephalus and traumatic brain injury: presented with behavioral symptoms similar to behavioral variant frontotemporal dementia

Objective: Traumatic brain injury (TBI) is nondegenerative insult to brain from external mechanical forces. It may cause cognitive impairment, psychological problems in the long period. Besides traumatic brain injury also induces neuroinflammation and neurodegeneration process, and increases risk of dementia. It may cause various psychiatric complications such as depression, posttraumatic stress disorder, generalized anxiety disorder, and other cognitive and behavioral sequela according to site of involvement in the brain.

Methods: We report a patient who has behavioral symptoms, amnesia and gait apraxy after TBI. Patient's symptoms were similar to behavioral variant Frontotemporal Dementia (bv FTD).

Results: After detailed neurocognitive and radiologic evaluation he was diagnosed with Normal Pressure Hydrocephalus (NPH), and Alzheimer's Disease (AD) following TBI.

Conclusion: Comprehensive geriatric assessment, including detailed radiological examinations, if it is necessary, is recommended for the optimum management of elderly patients with cognitive and psychosocial problems in order to avoid misdiagnosis and inappropriate treatment.     

大鼠脑损伤后NMDAR1表达及其认知障碍变化的关系

目的同步考量脑损伤后大鼠与认知功能较为密切的脑区N-甲基-D-天冬氨酸受体1（NMDAR1）表达与认知功能的变化。方法参照Feeney法建立大鼠创伤性脑损伤模型,伤后1d,2d,4d,7d1）．2免疫组化SABC法检测大鼠额叶皮质、海马区、基底前脑区NMDAR1表达,以行走实验、平衡实验及记忆功能测定评估大鼠认知障碍变化。结果轻、中型脑损伤组大鼠于伤后2d认知障碍最严重,分别于伤后3,7d基本恢复正常。轻型、中型脑损伤组脑额叶皮质、海马区、基底前脑区NMDAR1均于伤后1d升高,于2d降至较低水平后再呈缓慢增高趋势,与认知障碍变化趋势呈同步变化,且中型脑损伤组NMDAR1表达高于假手术组与轻型脑损伤组（P〈0．05）。结论大鼠经创伤性脑损伤后,额叶皮质、海马区、基底前脑区细胞中的NMDAR1含量和损伤后认知障碍的变化趋势有相似性;创伤性脑损伤后表达增加的NMDAR1对大鼠认知功能有加重损害作用。     

盐酸多奈哌齐治疗轻、中型脑外伤后认知障碍的临床研究

目的探讨盐酸多奈哌齐对轻、中型脑外伤患者伤后认知障碍及临床预后的影响。方法本组轻、中型脑外伤合并认知障碍患者78例,随机分成治疗组和对照组,治疗组应用盐酸多奈哌齐,对照组应用吡拉西坦,两组的治疗周期为12周。治疗前及治疗后分别应用简明精神状态检测量表（MMSE）、国人修订成人韦氏智力量表（WAIS-RC）和格拉斯哥预后评分（GOS）评价疗效。结果两组治疗后12周MMSE和WAIS-RC评分均较治疗前提高（P〈0.05）。治疗组MMSE和WAIS-RC评分提高较对照组明显（P〈0.05）,治疗组GOS预后优良率优于对照组（P〈0.05）。结论盐酸多奈哌齐对轻、中型脑外伤后认知障碍有积极治疗作用,并能改善临床预后。     

Correlation of brain-derived neurotrophic factor to cognitive impairment following traumatic brain injury in rats

BACKGROUND: In vitro and in vivo studies have confirmed that brain-derived neurotrophic factor (BDNF) can promote survival and differentiation of cholinergic, dopaminergic and motor neurons, and axonal regeneration. BDNF has neuroprotective effects on the nervous system. OBJECTIVE: To explore changes in BDNF expression and cognitive function in rats after brain injury DESIGN, TIME AND SETTING: The neuropathology experiment was performed at the Second Research Room, Department of Neurosurgery, Fujian Medical University (China) from July 2007 to July 2008. MATERIALS: A total of 72 healthy, male, Sprague Dawley, rats were selected for this study. METHODS: Rat models of mild and moderate traumatic brain injury were created by percussion, according to Feeney's method (n = 24, each group). A bone window was made in rats from the sham operation group (n = 24), but no attack was conducted. MAIN OUTCOME MEASURES: At days 1,2, 4 and 7 following injury, BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was examined by immunohistochemistry (streptavidin-biotin-peroxidase complex method). Changes in rat cognitive function were assessed by the walking test, balance-beam test and memory function detection. RESULTS: Cognitive impairment was aggravated at day 2, and recovered to normal at days 3 and 7 in rats from the mild and moderate traumatic brain injury groups. BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was increased at 1 day, decreased at day 2, and then gradually increased in the mild and moderate traumatic brain injury groups. BDNF expression was greater in rats from the moderate traumatic brain injury group than in the sham operation and mild traumatic brain injury groups (P < 0.05). CONCLUSION: BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain is correlated to cognitive impairment after traumatic brain injury. BDNF has a protective effect on cognitive function in rats following injury     

Correlation of brain-derived neurotrophic factor to cognitive impairment following traumatic brain injury in rats**☆

BACKGROUND： In vitro and in vivo studies have confirmed that brain-derived neurotrophic factor （BDNF） can promote survival and differentiation of cholinergic, dopaminergic and motor neurons, and axonal regeneration. BDNF has neuroprotective effects on the nervous system. OBJECTIVE： To explore changes in BDNF expression and cognitive function in rats after brain injury. DESIGN, TIME AND SETTING： The neuropathology experiment was performed at the Second Research Room, Department of Neurosurgery, Fujian Medical University （China） from July 2007 to July 2008. MATERIALS： A total of 72 healthy, male, Sprague Dawley, rats were selected for this study. METHODS： Rat models of mild and moderate traumatic brain injury were created by percussion, according to Feeney＇s method （n = 24, each group）. A bone window was made in rats from the sham operation group （n = 24）, but no attack was conducted. MAIN OUTCOME MEASURES： At days 1, 2, 4 and 7 following injury, BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was examined by immunohistochemistry （streptavidin-biotin-peroxidase complex method）. Changes in rat cognitive function were assessed by the walking test, balance-beam test and memory function detection. RESULTS： Cognitive impairment was aggravated at day 2, and recovered to normal at days 3 and 7 in rats from the mild and moderate traumatic brain injury groups. BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was increased at 1 day, decreased at day 2, and then gradually increased in the mild and moderate traumatic brain injury groups. BDNF expression was greater in rats from the moderate traumatic brain injury group than in the sham operation and mild traumatic brain injury groups （P 〈 0.05）. CONCLUSION： BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain is correlated to cognitive impairment after traumatic brain injury. BDNF has a protective effect on cognitive function in rats following i     

Mild cognitive impairment and everyday functioning in older adults

The relations between mild cognitive impairment without dementia (MCI/CIND) and everyday functional abilities were examined using data from the Canadian Study of Health and Aging (CSHA). Individuals were identified with MCI/CIND if both caregiver report and clinician judgment agreed on the presence of cognitive impairment in the absence of dementia. Cross-sectional and longitudinal comparisons indicated that individuals with MCI/CIND demonstrated a broad range of impairment in instrumental activities of daily living (IADL) compared to individuals with no cognitive impairment (NCI). In cross-sectional analyses, neuropsychological measures of memory and psychomotor speed were significantly related to impairment in eight areas of functioning. In addition, poorer memory performance was significantly predictive of future impairment in money management.     

氢质子磁共振波谱成像技术在创伤性脑损伤后认知障碍中的应用

创伤性脑损伤(TBI)可引起一系列复杂的病理生理过程变化,这些变化包括脑内物质代谢异常,导致机体出现包括头痛、认知、运动和情感障碍等在内的长、短期症状,而认知障碍是阻碍TBI患者日常生活质量恢复和延缓其回归社会的重要因素。氢质子磁共振波谱成像技术(1H-MRS)可对急、慢性脑部损伤患者的脑组织代谢进行非侵入性检测,具有辅助诊断和预测长期功能预后的价值。该文将近年来1H-MRS在TBI后认知障碍中的应用进行总结和展望。[国际神经病学神经外科学杂志, 2021, 48(2):197-201]     

Recurrent perseverations on semantic verbal fluency tasks as an early marker of cognitive impairment

Introduction: Our objective was to examine the association between perseverations produced on the semantic verbal fluency (SVF) task in asymptomatic individuals and the future diagnosis of cognitive impairment (CI).

Method: Participants were individuals participating in the Mayo Clinic Study of Aging (N = 1269, M_age = 79.3 years, SD = 5.1; 51% men). All were cognitively normal at baseline and were followed in 15-month intervals for up to 6 visits. Each neurocognitive assessment included SVF tasks (“animals,” “fruits,” and “vegetables”). Cox modeling was used to test for associations between perseverations and time to CI diagnosis.

Results: Perseverations on the “animals” SVF task were associated with incident CI (hazard ratio = 1.35; 95% confidence interval, CI [1.10, 1.66]). No significant association was found with perseverations on the “fruits” or “vegetables” SVF tasks. Mixed-effects modeling in cognitively normal participants revealed that the number of perseverations at baseline is significantly associated with decline in memory and visuospatial cognitive domains but is not associated with decline in attention.

Conclusions: Assessing perseverations together with standard SVF scores on the “animals” SVF task can help in early identification of asymptomatic individuals at an increased risk for CI. Perseverations are not associated with attention, but rather visual and verbal working memory mechanisms. In longitudinal settings aimed at early detection of signs of CI in presymptomatic individuals, SVF testing with scoring that includes counting of perseverations may potentially serve as a practical alternative to the more cumbersome memory tests.     

Association between cognitive impairments and obsessive-compulsive spectrum presentations following traumatic brain injury

This study examined the association between self-reported obsessive-compulsive spectrum symptomatology and cognitive performance in a sample of patients with traumatic brain injury (TBI). Twenty-four adults with a moderate-severe TBI accessing a community brain injury rehabilitation service were recruited. Age ranged between 19 and 69 years. Participants completed a battery of neuropsychological tasks assessing memory, executive functioning, and speed of information processing. Self-report questionnaires assessing obsessive-compulsive (OC) symptoms and obsessive-compulsive personality disorder (OCPD) traits were also completed. Correlational analyses revealed that deficits in cognitive flexibility were associated with greater self-reported OC symptomatology and severity. Greater OC symptom severity was significantly related to poorer performance on a visual memory task. Verbal memory and speed of information processing impairments were unrelated to OC symptoms. Performance on tasks of memory, executive functioning, and speed of information processing were not associated with OCPD traits. Overall, results indicate that greater OC symptomatology and severity were associated with specific neuropsychological functions (i.e., cognitive flexibility, visual memory). OCPD personality traits were unrelated to cognitive performance. Further research is needed to examine the potential causal relationship and longer-term interactions between cognitive sequelae and obsessive-compulsive spectrum presentations post-TBI.     

Added value and limitations of amyloid-PET imaging: review and analysis of selected cases of mild cognitive impairment and dementia

Amyloid-positron emission tomography (PET) imaging of the brain detects elevated amyloid-beta (amyloid-β) neuritic plaques in vivo, which can be helpful in appropriately selected cases of mild cognitive impairment (MCI) and dementia, when Alzheimer’s disease remains a possible etiology, after a comprehensive clinical evaluation. We reviewed cases of cognitively impaired patients who underwent amyloid-PET imaging because of diagnostic uncertainty. Pre- and post-PET elements of diagnosis and management were first compared, to assess impact of scan results on clinical decision-making, and then an analysis of those decisions was undertaken in appropriate clinical situations, to delineate the added value and limitations of amyloid-PET imaging. The potential benefits and limitations of this diagnostic tool are important to understand in an era when the utility of such scans in clinical practice is evolving.     

儿童脑外伤脑电图特征分析

目的探讨脑电图在儿童脑损伤中的应用价值及脑电图诊断标准与儿童伤后智力障碍的相关关系。方法对86例儿童脑外伤后行脑电图检测并给予儿童韦氏智力量表进行评分。结果中、重度异常脑电图的脑外伤患儿有显著的智力下降(P<0.05);对脑电图分级与智力评分采用Spearman秩相关分析,二者呈负相关。结论脑电图可以作为间接了解儿童脑外伤后智力水平的辅助指标。     

The source of cognitive complaints predicts diagnostic conversion differentially among nondemented older adults

ObjectiveThe objective of this study was to compare whether different sources of cognitive complaint (i.e., subjective and informant) predict diagnostic conversion in nondemented older adults.MethodsParticipants from the National Alzheimer's Coordinating Center had a baseline diagnosis of normal cognition (NC; n = 4414; mean age, 73 ± 8 years; 69% female) or mild cognitive impairment (MCI; n = 1843; mean age, 74 ± 8 years; 52% female). Multinomial logistic regression related baseline cognitive complaint (no complaint, self only, informant only, or both self and informant) to diagnostic outcome (reversion, stable, or conversion).ResultsAt follow-up, 14% of NC participants converted to MCI/dementia (3.5 ± 1.8 years), and 41% of MCI participants converted to dementia (3.0 ± 1.6 years). Among NC participants, self complaint only (odds ratio [OR], 2.1; 99% confidence interval (CI),1.5–2.9; P < .001), informant complaint only (OR, 2.2; 99% CI, 1.2–3.9; P < .001), and both self and informant complaint (OR, 4.2; 99% CI, 2.9–6.0; P < .001) were associated with diagnostic conversion compared with no complaint. Among participants with MCI—compared with no complaint, informant complaint only (OR, 2.2; 99% CI, 1.2–4.3, P = .002), and both self and informant complaint (OR, 2.9; 99% CI, 1.8–4.8; P < .001)—were associated with conversion.ConclusionsCognitive complaints are related to conversion among nondemented older adults. Complaint from both (i.e. mutual complaint) sources was most predictive of diagnostic outcome, followed by informant complaint, highlighting the need for obtaining informant corroboration to enhance prognosis and distinguish underlying pathological processes from normal cognitive aging. Self complaint was related inconsistently to diagnostic outcome.     

Longitudinal study of objective and subjective cognitive performance and psychological distress in OEF/OIF Veterans with and without traumatic brain injury

Objective: To describe changes in post-deployment objective and subjective cognitive performance in combat Veterans over 18 months, relative to traumatic brain injury (TBI) status and psychological distress. Method: This prospective cohort study examined 500 Veterans from Upstate New York at four time points, six months apart. TBI status was determined by a structured clinical interview. Neuropsychological instruments focused on attention, memory, and executive functions. Subjective cognitive complaints were assessed with the Neurobehavioral Symptom Inventory (NSI). A psychological distress composite included measures of post-traumatic stress disorder (PTSD), depression, and generalized anxiety. Results: Forty-four percent of the sample was found to have sustained military-related TBI, 97% of which were classified as mild (mTBI), with a mean time since injury of 41 months. Veterans with TBI endorsed moderate cognitive symptoms on the NSI. In contrast to these subjective complaints, mean cognitive test performance was within normal limits at each time point in all domains, regardless of TBI status. Multilevel models examined effects of TBI status, time, and psychological distress. Psychological distress was a strong predictor of all cognitive domains, especially the subjective domain. Substantial proportions of both TBI+ and TBI? groups remained in the clinically significant range at the initial and final assessment for all three distress measures, but the TBI+ group had higher proportions of clinically significant cases. Conclusions: Objective cognitive performance was generally within normal limits for Veterans with mTBI across all assessments. Psychological distress was elevated and significantly related to both objective and subjective cognitive performance.     

Diagnostic accuracy of the Phototest for cognitive impairment and dementia in Argentina

Phototest is a simple, easy and very brief test with theoretical advantages over available dementia screening tests in Spain. The objective of this study was to estimate the diagnostic accuracy of the Phototest for cognitive impairment and dementia and to compare it with that of the MMSE and the Clock Drawing Test (CDT) in an Argentine population. A phase II cross-sectional study of diagnostic tests evaluation was performed in a sample of 30 controls, 61 with amnestic mild cognitive impairment (a-MCI), and 56 with mild Alzheimer type dementia (DAT). The diagnostic accuracy (DA) was assessed in relation to the clinical diagnosis by calculating the area under the ROC curve (UAC), Sensitivity (Sn), and Specificity (Sp).The DA of the Phototest for a-MCI and DAT (0.93 and 0.97 [UAC]) was higher than that of the MMSE and the CDT. The cut-off points of 27/28 for DAT (Sn = 89.29 [78.1–96.0], Sp = 96.67 [82.8–99.9]) and 30/31 for a-MCI (Sn = 85.25 [73.8–93.0], Sp = 90.00 [73.5–97.9]) maximized the sum of Sn and Sp. Phototest correlates significantly with MMSE and CDT. The Phototest is an efficient instrument for the detection of mild dementia or MCI, with good accuracy and good correlation with tests measuring overall cognitive impairment.     

Novel microglia-mediated mechanisms underlying synaptic loss and cognitive impairment after traumatic brain injury

Traumatic brain injury (TBI) is one of the leading causes of long-term neurological disability in the world. Currently, there are no therapeutics for treating the deleterious consequences of brain trauma; this is in part due to a lack of complete understanding of cellular processes that underlie TBI-related pathologies. Following TBI, microglia, the brain resident immune cells, turn into a “reactive” state characterized by the production of inflammatory mediators that contribute to the development of cognitive deficits. Utilizing multimodal, state-of-the-art techniques that widely span from ultrastructural analysis to optogenetic interrogation of circuit function, we investigated the reactive microglia phenotype one week after injury when learning and memory deficits are also measured. Microglia displayed increased: (i) phagocytic activity in vivo, (ii) synaptic engulfment, (iii) increased neuronal contact, including with dendrites and somata (termed ‘satellite microglia’). Functionally, satellite microglia might impact somatic inhibition as demonstrated by the associated reduction in inhibitory synaptic drive. Cumulatively, here we demonstrate novel microglia-mediated mechanisms that may contribute to synaptic loss and cognitive impairment after traumatic brain injury.     

弥散张量成像技术预测遗忘型轻度认知障碍患者向老年性痴呆转化的随访研究

目的:探讨弥散张量成像技术(diffusion tensor imaging,DTI)对遗忘型轻度认知功能障碍(aMCI)向老年性痴呆(AD)转化的预测作用。方法:41例aMCI患者(aMCI组)常规予核磁共振(MRI)和DTI扫描,测定感兴趣区的各向异性分数(fractional anisotropy,FA)和表观扩散系数(apparent diffusion coefficient,ADC),以20名老年健康志愿者作为对照(正常对照组)并随访1~3年。结果:与正常对照组比较,aMCI组41例患者中有22例扣带束FA基线值偏低(P0.05),随访1~3年后,其中有19例转化为AD;另外19例扣带束FA值正常的aMCI患者只有2例转化为AD。与非转化AD者比较,AD转化者前额叶、颞叶、海马、下额枕束、胼胝体膝部和扣带束等部位FA值降低(P均0.01),颞叶、海马等部位ADC值升高(P均0.05)。结论:DTI技术具有预测aMCI向AD转化的作用,aMCI患者扣带束FA值低可能是aMCI向AD转化的敏感指标。