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Background: The use of biomarkers, in particular amyloid-β (Aβ) changes, has allowed the possibility to identify patients with subjective memory complaints (SMCs) and amnestic mild cognitive impairment (aMCI) who suffer from Alzheimer's disease (AD). Since it is unfeasible that all patients with aMCI could presently undergo biomarkers assessment, it would be important that SMCs might contribute to identify the aMCI patients who have AD amyloid pathology., Objectives: To know whether aMCI patients with amyloid biomarkers (Aβ+) present greater SMCs as compared to those without amyloid biomarkers (Aβ-)., Methods: Participants were selected from a cohort of nondemented patients with cognitive complaints and a comprehensive neuropsychological evaluation, on the basis of 1) diagnosis of aMCI; 2) detailed assessment of memory difficulties with the SMC Scale; and 3) known amyloid status. The amyloid status was determined on the basis of either CSF Aβ1-42 concentration or amyloid PET imaging., Results: Of the 176 patients with aMCI studied, 90 were Aβ+ and 86 were Aβ-. The two groups did not differ in terms of age, gender, and education. The SMC total score was not significantly different in the Aβ+ aMCI patients (9.48±4.18) when compared to the Aβ- aMCI patients (10.52±4.57). The Aβ+ aMCI patients had lower scores on the MMSE and memory/learning tests, but not on the Geriatric Depression Scale, when comparing to the Aβ- aMCI patients., Conclusions: Evaluating SMCs does not seem helpful to identify, among patients with aMCI, those who have AD.

Background: Scales of global cognition and behavior, often used as endpoints for intervention trials in Alzheimer's disease (AD) and mild cognitive impairment (MCI), are insufficiently responsive (i.e., relatively insensitive to change). Large patient samples are needed to detect beneficial drug effects. Therefore, magnetic resonance imaging (MRI) measures of cerebral atrophy have been proposed as surrogate endpoints., Objective: To examine how neuropsychological assessment compares to MRI in this respect., Methods: We measured hippocampal atrophy, cortical thickness, and performance on neuropsychological tests in memory clinic patients at baseline and after two years. Neurologists rated the patients as cognitively normal (n = 28; Clinical Dementia Rating, CDR = 0) or as impaired (n = 34; CDR > 0). We administered five tests of memory, executive functioning, and verbal fluency. A composite neuropsychological score was calculated by taking the mean of the demographically corrected standard scores. MRI was done on a 3 Tesla scanner. Volumetric measurements of the hippocampus and surrounding cortex were made automatically using FreeSurfer software., Results: The composite neuropsychological score deteriorated 0.6 SD in the impaired group, and was virtually unchanged in the normal group. Annual hippocampal atrophy rates were 3.4% and 0.6% in the impaired and normal cognition groups, respectively. Estimates of required sample sizes to detect a 50% reduction in rate of change were larger using rate of hippocampal atrophy (n = 131) or cortical thickness (n = 488) as outcome compared to change scores on neuropsychological assessment (n = 62)., Conclusion: Neuropsychological assessment is more responsive than MRI measures of brain atrophy for detecting disease progression in memory clinic patients with MCI or AD.

Using the database of the Alzheimer's Disease Neuroimaging Initiative, we examined the value of neuropsychological assessment, structural magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) biomarkers, and FDG-PET scanning with respect to prediction of conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). We tested the hypothesis that CSF biomarkers and FDG-PET would lose prognostic value when applied in patients older than 75 years, whereas MRI and neuropsychological testing would not. At baseline 175 patients had MCI, mostly amnestic. They were followed during a mean of 2.7 years, and 81 patients converted to AD after a mean of 1.6 years. Logistic regression analyses showed that neuropsychological assessment and MRI variables predicted conversion with 63 to 67% classification success both in patients younger and older than 75 years, while CSF biomarkers attained this success rate only in patients younger than 75 years. For FDG-PET, this rate was 57% in the total sample. We conclude that the diagnostic yield of different techniques in predicting conversion from MCI to AD is moderate, and that it is affected by age of the subject under study. MRI and neuropsychological assessment remain informative in patients older than 75 years, unlike CSF biomarkers.

The focus of most of the research on Alzheimer's disease in the last decades has been on senile plaques and neurofibrillary tangles. The vast majority of patients with Alzheimer's disease are over 75 years of age, whereas most of the research focuses on younger subjects. To consider old-age dementia as a homogenous well-defined condition ignores the complexity of this condition and limits the development of new diagnostic methods, preventive strategies, or treatment strategies that could be widely applicable in daily practice in the majority of the older patients. The current research on biomarkers focuses on correlates of plaques and tangles, which are poor markers in older dementia subjects. Acknowledging that dementia in old age is an essentially different condition from dementia at relatively younger age is needed and should lead to new approaches in dementia research.

Longer cognitive tests, such as the Alzheimer's disease assessment scale (ADAS-cog) or the Cambridge cognitive examination (CAMCOG), are more precise but less efficient than briefer tests, such as the Mini Mental State Examination (MMSE). We examined if computerized adaptive testing (CAT) of cognitive impairment can combine brevity with precision by tailoring a precise test to each individual patient. We conducted a prospective study of 84 participants [normal aging, n = 41; mild cognitive impairment (MCI), n = 21; dementia, n = 22]. CAT estimated a participant's ability during testing by selecting only items of appropriate difficulty from either the CAMCOG or the CAMCOG supplemented with ADAS-cog items and neuropsychological tests (the CAMCOG-Plus). After tailored testing with CAT, the remaining CAMCOG and CAMCOG-Plus items not selected by CAT were administered. The time needed to complete the CAT was compared to that needed for the whole CAMCOG and CAMCOG-Plus. Results showed that testing time reductions achieved with CAT were 37% or more compared to the whole CAMCOG and 55% or more compared to the whole CAMCOG-Plus. Estimated ability levels with CAT were in excellent agreement with those based on the whole CAMCOG and CAMCOG-Plus (intraclass correlations 0.99 and 0.98, respectively). Diagnostic accuracy of detecting mild dementia and MCI seemed better for the CAT administered tests than for the MMSE, but the differences were not significant. We conclude that adaptive testing combines brevity with precision, especially in grading the severity of cognitive impairment.

Although 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) has been shown to damage brain serotonin (5-HT) neurons in animals and possibly humans, little is known about the long-term consequences of MDMA-induced 5-HT neurotoxic lesions on functions in which 5-HT is involved, such as cognitive function. Because 5-HT transporters play a key element in the regulation of synaptic 5-HT transmission it may be important to control for the potential covariance effect of a polymorphism in the 5-HT transporter promoter gene region (5-HTTLPR) when studying the effects of MDMA as well as cognitive functioning. The aim of the study was to investigate the effects of moderate and heavy MDMA use on cognitive function, as well as the effects of long-term abstention from MDMA, in subjects genotyped for 5-HTTLPR. A second aim of the study was to determine whether these effects differ for females and males. Fifteen moderate MDMA users (<55 lifetime tablets), 22 heavy MDMA+ users (>55 lifetime tablets), 16 ex-MDMA+ users (last tablet > 1 year ago) and 13 controls were compared on a battery of neuropsychological tests. DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods.A significant group effect was observed only on memory function tasks (p = 0.04) but not on reaction times (p = 0.61) or attention/executive functioning (p = 0.59). Heavy and ex-MDMA+ users performed significantly poorer on memory tasks than controls. In contrast, no evidence of memory impairment was observed in moderate MDMA users. No significant effect of 5-HTTLPR or gender was observed. While the use of MDMA in quantities that may be considered "moderate" is not associated with impaired memory functioning, heavy use of MDMA use may lead to long lasting memory impairments. No effect of 5-HTTLPR or gender on memory function or MDMA use was observed.