Cognitive and brain cytokine profile of non-demented individuals with cerebral amyloid-beta deposition.

BACKGROUND: Brain inflammation has been increasingly associated with early amyloid accumulation in Alzheimer's disease models; however, evidence of its occurrence in humans remains scarce. To elucidate whether amyloid deposition is associated with neuroinflammation and cognitive deficits, we studied brain inflammatory cytokine expression and cognitive decline in non-demented elderly individuals with and without cerebral amyloid-beta deposition. METHODS: Global cognition, episodic, working, and semantic memory, perceptual speed, visuospatial ability, and longitudinal decline (5.7 ± 3.6 years) in each cognitive domain were compared between elderly individuals (66-79 years) with and without cerebral amyloid-beta deposition. The expression of 20 inflammatory cytokines was analyzed in frozen temporal, parietal, and frontal cortices and compared between older individuals with and without amyloid-beta deposition in each brain region. Correlation analyses were performed to analyze associations between amyloid-beta load, cytokine expression, and cognitive decline. RESULTS: Individuals with cortical amyloid-beta deposition displayed deficits and a faster rate of cognitive decline in perceptual speed as compared with those individuals without amyloid-beta. This decline was positively associated with cortical amyloid-beta levels. Elderly individuals with amyloid-beta deposition had higher levels of IL-1ß, IL-6, and eotaxin-3 in the temporal cortex accompanied by an increase in MCP-1 and IL-1ß in the parietal cortex and a trend towards higher levels of IL-1ß and MCP-1 in the frontal cortex as compared with age-matched amyloid-free individuals. Brain IL-1ß levels displayed a positive association with cortical amyloid burden in each brain region. Finally, differential cytokine expression in each cortical region was associated with cognitive decline. CONCLUSIONS: Elderly individuals with amyloid-beta neuropathology but no symptomatic manifestation of dementia, exhibit cognitive decline and increased brain cytokine expression. Such observations suggest that increased cytokine expression might be an early event in the Alzheimer's continuum.

Psychometric Properties of the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network Neuropsychological Battery in an Asian Older Adult Sample.

OBJECTIVE: Despite the wide usage of the National Institute of Neurological Disorders and Stroke and Canadian Stroke Network (NINDS-CSN) neuropsychological battery for the detection of vascular cognitive impairment, its reliability and validity have not been established. Therefore, the present study established the psychometric properties of the battery in cognitively normal older adults in a clinical setting in Singapore. DESIGN: Longitudinal study. SETTING AND PARTICIPANTS: A total of 105 cognitively normal older adults age 50 years and older were assessed in a memory clinic setting. METHODS: The 60-minute NINDS-CSN and 5-minute protocol were administered to participants at baseline and 3-month follow-up. Raw scores were transformed into standardized z scores. Test-retest reliability, concurrent validity and construct (convergent and discriminant) validity were reported. RESULTS: Moderate-to-excellent test-retest reliability (r = 0.36-0.87), concurrent validity, and construct validity (r = 0.41-0.83) were found in both protocols over 3 months (all Ps < 0.01). Although the 5-minute protocol showed moderate validity (r = 0.41), the 60-minute protocol had excellent concurrent validity against a locally validated neuropsychological battery (r = 0.83). CONCLUSION AND IMPLICATIONS: The NINDS-CSN is reliable and valid in assessing cognitive function. The 60-minute protocol demonstrates great utility beyond its current usage in vascular cognitive impairment populations to the general older adult population. The 5-minute protocol can be used as a brief cognitive screening tool in primary healthcare and the community, due to its brevity and accuracy. Future research should further examine the generalizability of the NINDS-CSN battery in other dementias and cognitive disorders.

Static and Dynamic Cognitive Reserve Proxy Measures: Interactions with Alzheimer's Disease Neuropathology and Cognition.

OBJECTIVE: Years of education are the most common proxy for measuring cognitive reserve (CR) when assessing the relationship between Alzheimer's disease (AD) neuropathology and cognition. However, years of education may be limited as a CR proxy given that it represents a specific timeframe in early life and is static. Studies suggest that measures of intellectual function provide a dynamic estimate of CR that is superior to years of education since it captures the effect of continued learning over time. The present study determined whether dynamic measures of CR were better predictors of episodic memory and executive function in the presence of AD pathology than a static measure of CR. METHODS: Subjects examined died with a pre-mortem clinical diagnosis of no cognitive impaired, mild cognitive impairment and mild to moderate AD. CERAD and Braak stage were used to stratify the sample by AD pathology severity. Linear regression analyses using CR by CERAD and CR by Braak stage interaction terms were used to determine whether Extended Range Vocabulary Test (ERVT) scores or years of education were significantly associated with episodic memory composite (EMC) and executive function composite (EFC) performance. All models were adjusted for clinical diagnosis, age at death, gender, APOE e4 carrier status and Braak stage. RESULTS: For episodic memory, years of education by CERAD interaction were not statistically significant (ß=-0.01, SE=0.01, p=0.53). By contrast, ERVT interaction with CERAD diagnosis was statistically significant (ß=-0.03, SE=0.01, p=0.004). Among the models using Braak stages, none of the CR by pathology interactions were associated with EMC or EFC. CONCLUSION: Results suggest that a dynamic rather than a static measure is a better indicator of CR and that the relationship between CR and cognition is dependent upon the severity of select AD criteria.

Interhemispheric connectivity in amyotrophic lateral sclerosis: A near-infrared spectroscopy and diffusion tensor imaging study.

PURPOSE: Aim of the present study was to investigate potential impairment of non-motor areas in amyotrophic lateral sclerosis (ALS) using near-infrared spectroscopy (NIRS) and diffusion tensor imaging (DTI). In particular, we evaluated whether homotopic resting-state functional connectivity (rs-FC) of non-motor associated cortical areas correlates with clinical parameters and disease-specific degeneration of the corpus callosum (CC) in ALS. MATERIAL AND METHODS: Interhemispheric homotopic rs-FC was assessed in 31 patients and 30 healthy controls (HCs) for 8 cortical sites, from prefrontal to occipital cortex, using NIRS. DTI was performed in a subgroup of 21 patients. All patients were evaluated for cognitive dysfunction in the executive, memory, and visuospatial domains. RESULTS: ALS patients displayed an altered spatial pattern of correlation between homotopic rs-FC values when compared to HCs (p = 0.000013). In patients without executive dysfunction a strong correlation existed between the rate of motor decline and homotopic rs-FC of the anterior temporal lobes (ATLs) (ρ = - 0.85, p = 0.0004). Furthermore, antero-temporal homotopic rs-FC correlated with fractional anisotropy in the central corpus callosum (CC), corticospinal tracts (CSTs), and forceps minor as determined by DTI (p < 0.05). CONCLUSIONS: The present study further supports involvement of non-motor areas in ALS. Our results render homotopic rs-FC as assessed by NIRS a potential clinical marker for disease progression rate in ALS patients without executive dysfunction and a potential anatomical marker for ALS-specific degeneration of the CC and CSTs.

The effects of educational background on Montreal Cognitive Assessment screening for vascular cognitive impairment, no dementia, caused by ischemic stroke.

It is possible that a patient's educational background has an effect on their Montreal Cognitive Assessment (MoCA) score, which is used to evaluate patients for vascular cognitive impairment, no dementia (VCIND) after ischemic stroke. Cognitive impairment was evaluated in patients with no cognitive impairment (NCI) or VCIND using the MoCA. The receiver operating characteristic curve and maximal Youden index were used to determine the optimal cut-off values to distinguish between NCI and VCIND. The sensitivity and specificity of MoCA were calculated for patients with primary, secondary and tertiary educational levels. Patients with NCI (n=111) and VCIND (n=95) were tested. In patients with a primary education, a significant difference was found between the two groups in each of the MoCA factors, except for naming. Likewise, a significant difference was found in all factors, except for naming, attention and calculation, for patients with a secondary education. For the patients with a tertiary education, a significant difference was found only in visuospatial/executive abilities, abstraction and memory (p<0.05). The optimal cut-off value for MoCA in order to identify VCIND was 22-23. MoCA showed an overall sensitivity of 65.26% and specificity of 78.73%. The sensitivity in the primary, secondary and tertiary educated groups was 97.06%, 56.10% and 40%, respectively, with the specificity being 47.22%, 87.80% and 100%, respectively. We suggest that the MoCA score needs to be amended according to the patient's educational levels in order to improve the effectiveness of the screening.