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Recent study has suggested semantic memory deterioration may be the earliest cognitive changes in Alzheimer's disease (AD). Few previous researchers have investigated specific changes in the semantic structures in the memory of patients with amnestic mild cognitive impairment (aMCI). This study examined the clustering performance in semantic fluency among 160 participants in various MCI subgroups (aMCI single domain, aMCI-sd, n = 30; aMCI multiple domain, aMCI-md, n = 30; non-aMCI multiple domain, naMCI-md, n = 10) as well as a group of mildly impaired individuals with dementia of AD type (DAT, n = 20), and a group of healthy controls (HC, n = 70). Compared with HC group, DAT patients presented deficient clustering in each semantic category related to living things. aMCI-sd group presented defective clustering when dealing with the clustering of items that may be more strongly associated with praxis and perceptual information in the categories that included inanimate living things. aMCI-md group displayed defective patterns similar to those in the aMCI-sd group; however, they displayed more profound deficits in clustering that may require perceptual information. Patients with naMCI-md preserved their ability to perform clustering on all of the categories. The poor clustering of items that may be more strongly associated with praxis could be used as a means of predicting conversion from aMCI-sd to DAT, whereas performance on items that may require perceptual information could be used to predict conversion among aMCI-md patients. These findings demonstrate the degree to which the semantic structures in memory can be used for the assessment of aMCI patients and prediction of conversion to DAT.

Background Optimization of vascular risk factor control is emerging as an alternative approach to improve cognitive outcomes in Alzheimer’s disease, although its efficacy is still under debate. We aimed to investigate the contribution of vascular risk factors on Alzheimer’s biomarkers and conversion rate to dementia in subjects with mild cognitive impairment (MCI) with low cerebral small vessel disease burden. Methods Two hundred ninety-five newly diagnosed MCI subjects were enrolled from March 2005 to May 2017 for a cross-sectional assessment of vascular risk factors and Alzheimer’s plasma and imaging biomarkers, followed by a cognitive outcome assessment 24 months after enrollment. The association between vascular risk factors and Alzheimer’s biomarkers were tested using multivariable linear regression models adjusted with age, gender, education, and APOE ε4 allele. The association between vascular risk factors and conversion to dementia was tested using multivariable logistic regression models adjusted with age, gender, education, and baseline Mini-Mental State Examination (MMSE) score. Results At baseline, higher low-density lipoprotein (LDL) cholesterol level was associated with more advanced plasma biomarkers, including Aβ42/Aβ40 ratio (P = 0.012) and tau level (P = 0.001). A history of hypertension was associated with more advanced white matter hyperintensity (P = 0.011), while statin therapy for dyslipidemia was associated with less advanced white matter hyperintensity (P = 0.002). At 24 months, individual vascular risk factor was not significantly associated with cognitive outcome. By contrast, statin therapy for dyslipidemia was associated with reduced conversion to dementia (adjusted OR = 0.191, 95% CI = 0.062~0.586, P = 0.004). Conclusions For MCI subjects, dyslipidemia may contribute to AD-related neurodegeneration while hypertension may contribute to vascular pathology. The association between statin therapy for dyslipidemia and reduced conversion to dementia supports further interventional study to evaluate the potential beneficial effect of statin in MCI subjects.

Objective Evaluating social-functioning impairments in patients with Alzheimer's disease (AD) objectively is essential for clinical service. However, the existing instruments lack representative content, consensus on purposes of use, and adequate scoring systems and samples. This study was thus to develop a social functioning scale for patients: the Social Functioning Scale for Alzheimer's Disease (SFSAD). Method Questionnaires were analyzed from 142 AD patients, 30 patients with amnestic mild cognitive impairment (aMCI), and 50 normal controls. Results Based on the literature review and experts' opinions, the final scale includes 20 items in four subscales. The SFSAD showed high internal consistency coefficients (Cronbach's α = .97) and test-retest reliability (r = .99) coefficients. The content validity was desirable, and the criterion-related validity was demonstrated by a significant association with the MMSE, the IADL, and the Barthel ADL. The discriminant validity of the scale was also demonstrated as the level of social-functioning impairment was significantly related to the degree of dementia, and for construct validity, our findings supported the structure of the four-factor hypothesized model. Conclusions The SFSAD is thus a practical, psychometrically sound, and easy-to-administer measure to evaluate social functioning of AD and aMCI in brisk clinical settings.

Background/Purpose: Researchers have recently proposed a preclinical stage of dementia of Alzheimer's type (DAT), referred to as subjective memory impairment (SMI), with the aim of developing methods for the early detection of DAT and subsequent intervention. It has been proposed that the objective memory functions of individuals with SMI are normal; however, arbitrary and semantic associations are both used to describe the processes of memory. No previous studies have investigated these processes among individuals with SMI. Methods: Cross-sectional analysis was used to compare the memory function of individuals with SMI, amnestic mild cognitive impairment (aMCI), or DAT. One hundred and eighty-three participants were recruited from the Memory Clinic of National Taiwan University Hospital and communities in northern Taiwan, including individuals with no memory complaints (HC, n = 30) and individuals with SMI (n = 61), aMCI-single domain (n = 24), aMCI-multiple domain (n = 33), or DAT (n = 35). The Word Sequence Learning Test (WSLT) was used to assess the formation of arbitrary associations and the Logical Memory subtest of the Wechsler Memory Scale-Third Edition was used to assess the formation of semantic associations. Results: Compared to the HC group, the SMI group performed poorly only on the WSLT, whereas the other groups performed poorly on both of the memory tasks. This study demonstrated that SMI individuals tend to perform poorly in the formation of arbitrary associations. Conclusion: Our findings suggest that tasks requiring arbitrary associations may provide greater sensitivity in the detection cognitive changes associated with preclinical DAT. Keywords: Alzheimer's disease, Mild cognitive impairment, Neuropsychology, Dementia

Our aim in this study was to explore the neural substrates of executive function in frontal and nonfrontal white matter using diffusion tensor imaging (DTI). We studied the relationship between executive dysfunction and DTI measurements on 13 subjects with amnesic mild cognitive impairment (aMCI), 11 subjects with early Alzheimer's disease (AD), and 16 control subjects. All participants underwent an examination of their intelligence, memory, and executive function and were subjected to DTI. Both aMCI and early AD subjects showed executive function impairment with differential performance in frontal‐related behaviors. Both aMCI and early AD subjects showed increased mean diffusivity in the genu of the corpus callosum and left frontal periventricular white matter (PVWM), whereas subjects with early AD showed an additional decrease in the fractional anisotropy of bilateral frontal PVWM and in the genu of the corpus callosum. The frontal PVWM was associated with performance on the Verbal Fluency Test, the Wisconsin Card Sorting Test (WCST), and Part B of the Trail Making Test. The parietal PVWM was associated with perseverative errors on the WCST and Part A of the Trail Making Test. In summary, executive function was impaired in subjects with aMCI and early AD and was associated with frontal and parietal PVWM changes. These changes may be due to early AD degeneration of the lateral cholinergic projections or to early change of the superior longitudinal fasciculus. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.

Limited research has investigated the effects of executive dysfunction on semantic memory deterioration among patients with amnestic mild cognitive impairment (aMCI). This study examined the cognitive performance of 181 participants from various MCI subgroups, a group of mildly impaired individuals with dementia of the Alzheimer type (DAT) and a group of individuals with subjective memory impairment on various semantic memory tasks. The aMCI-single domain (aMCI-sd) group displayed poor performance on a semantic memory task requiring relatively higher degrees of effortful retrieval, and participants in the aMCI-multiple domain (aMCI-md) group, who also suffered with mild executive dysfunction displayed poor performance on all semantic memory tasks, similar to the DAT group. The nonamnestic MCI (non-a-MCI)-single domain group displayed normal performance across all semantic tasks, whereas the non-a-MCI-multiple domain group displayed a pattern similar to that of the aMCI-sd group. aMCI-sd patients who displayed poor performance on the semantic memory task had higher risk of conversion to DAT, whereas poor performance on tasks requiring relatively less effortful retrieval was associated with higher risk of conversion in the aMCI-md group. Thus, executive function may relate to deterioration of semantic memory retrieval processes. Such patterns of semantic memory impairment could be valuable for characterization of cognitive differences among MCI patients.

Given the importance of early detection and intervention for disease management, determining the vulnerable neuropsychological function in patients with early-stage Parkinson's disease (PD) is a priority. Here, we describe the neuropsychological pattern in early-stage PD patients with mild cognitive impairment (PD-MCI) and dementia (PDD) in Taiwanese population. The neuropsychological performance of 94 patients with PD was compared with that of 84 healthy controls (HCs) and available normative data, using a comprehensive neuropsychological assessment including tests of executive, memory, psychomotor speed, attention, visuospatial, and language functions. Our results showed that PD patients performed significantly worse on executive function (i.e., category of card sorting) and psychomotor speed (i.e., processing speed index). Up to 46.8% were classified as PD-MCI and the majority of those having single-domain impairment (68.2%); 9.6% met the consensus diagnostic criteria for PDD. Accordingly, we suggest that early-stage PD patients have cognitive dysfunction predominately in the anterior brain. Further follow-up study to determine how many percent of PD-MCI develop PDD is important. The effect of neurocognitive rehabilitation on executive function is also valuable in the subsequence study.