Distribution of Cerebrospinal Fluid Biomarker Profiles in Patients Explored for Cognitive Disorders.

BACKGROUND: CSF Alzheimer's disease (AD) biomarkers allow classifying individuals based on their levels of amyloid and neurodegeneration pathologies. OBJECTIVE: To investigate the distribution of AD biomarker profiles from patients suffering from cognitive disorders. METHODS: We analyzed 3001 patients with cognitive disorders and referred by 18 French memory clinics located in and around Paris. Patients were classified as normal, amyloidosis (A+/N-), amyloidosis and neurodegeneration (A+/N+) or suspected non-AD pathophysiology (SNAP), according to their CSF levels of biomarkers. Analysis were performed for the overall population and stratified by gender, age quintiles, and Mini-Mental State Examination (MMSE) score quintiles. Results were compared to previous findings in cohorts of healthy elderly adults. RESULTS: 37% of the sample were classified as A+/N+, 22% were classified A+/N-, and 15% as SNAP. The A+/N+ profile was associated with female gender, advanced age, and lower MMSE score, while the A+/N-profile was observed more frequently in men and the distribution was stable across age and MMSE. The SNAP profile showed no association with gender or age, was less frequent in patients with lower MMSE, and had a lower repartition than the one previously reported in asymptomatic populations. CONCLUSIONS: While A+/N+ patients had the clinical characteristics typically observed in AD, A+/N-patients had a different epidemiological pattern (higher frequency in men, no association with advanced age or lower MMSE). The SNAP profile was less frequent than previously reported in the general elderly population, suggesting that this profile is not a frequent cause of memory impairment in this population.

[Vitamin D and neuropsychological assessment of cognitive functions: a study of their relationships in a sample of 244 patients attending a memory clinic]. / Vitamine D et évaluation neuropsychologique des fonctions cognitives : étude chez 244 sujets âgés pris en charge en hôpital de jour mémoire.

There is evidence of a role of vitamin D in cognitive functioning, but little is known about the type of functions involved. To describe vitamin D status in a population of old patients with memory complaints and its relationships with cognitive performance and white matter lesions. A retrospective single-centre observational study from the medical records of 244 patients who had a measurement of serum 25OHD together with a battery of neuropsychological tests during a complete geriatric and memory assessment in a day care hospital. The results of the 10 neuropsychological tests considered in this study were analysed as binary variables, opposing patients with results within the highest two tertiles to patients with the worse results or unable to perform the test. Mean age of people included was 80.2 ± 8.1 years and 64% of patients were women. Severe deficiency in vitamin D (25OHD <10 ng/mL) was found in 34 patients (13.9%) and moderate deficiency (10 ≤ 25OHD < 30 ng/mL) in 148 (60.7%). Compared to subjects with sufficient concentrations in vitamin D, patients with severe deficiency performed significantly worse on a global test, the Mini mental state examination, and two tests of verbal memory, the 5 words and the 16-item free and cued recall, independently from age, gender, education, body mass index and autonomy (OR = 2.85 [1.04-7.85], 4.31 [1.42-13.07], and 3.04 [1.01-9.19] respectively). Levels of vitamin D did not differ according to the extent of white matter lesions, visualized semi-quantitatively on magnetic resonance imaging of 115 subjects. This study confirms the high prevalence of vitamin D deficiency in elderly population and suggests a link between vitamin D deficiency and memory.

Brain perfusion SPECT with an automated quantitative tool can identify prodromal Alzheimer's disease among patients with mild cognitive impairment.

OBJECTIVE: To improve diagnosis of early Alzheimer's disease (AD), i.e., prodromal AD, by an automated quantitative tool combining brain perfusion single-photon emission computed tomography (SPECT) images and memory tests scores in order to be applied in clinical practice. PATIENTS AND METHODS: In this prospective, longitudinal, multi-centric study, a baseline (99m)Tc-ECD perfusion SPECT was performed in 83 patients with memory complaint and mild cognitive impairment (MCI). After a 3-year follow-up, 11 patients progressed to Alzheimer's disease (MCI-AD group), and 72 patients remained stable (MCI-S group), including 1 patient who developed mild vascular cognitive impairment. After comparison between the MCI-S and MCI-AD groups with a voxel-based approach, region masks were extracted from the statistically significant clusters and used alone or in combination with Free and Cued Selective Reminding Test (FCSRT) scores for the subject's categorization using linear discriminant analysis. Results were validated using the leave-one-out cross-validation method. RESULTS: Right parietal and hippocampal perfusion was significantly (p<0.05, corrected) decreased in the MCI-AD group as compared to the MCI-S group. The patients' classification in the MCI group using the mean activity in right and left parietal cortex and hippocampus yielded a sensitivity, specificity, and accuracy of 82%, 90%, and 89%, respectively. Combination of SPECT results and FCSRT free recall scores increased specificity to 93%. CONCLUSION: The combination of an automated quantitative tool for brain perfusion SPECT images and memory test scores was able to distinguish, in a group of amnestic MCI, patients at an early stage of AD from patients with stable MCI.

[Relationships between weight loss and circulating cytokines in patients with Alzheimer's disease]. / Amaigrissement et cytokines circulantes chez des patients souffrant d'une maladie d'Alzheimer.

106 consecutive patients with Alzheimer's disease living in the community were examined in a memory clinic from a neurological department. They were screened for weight loss over the last 2 years. Age, duration of the disease, behavioral disorders, mini mental status examination, body mass index were recorded. Tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), interleukin 6 (IL-6) and interleukin 2 (IL-2) blood levels were measured. Weight loss was reported in 42.5% of the patients. TNFalpha levels were significantly higher in these patients (18.8 versus 15.8 pg/mL; p=0.04) than in patients without weight loss. Weight loss was also associated with a lower MMSE score (16.9 versus 19.3; p=0.03), current pacing (20% versus 1.6%; p=0.002), and hallucinations (20.0% versus 3.3%; p=0.008). The levels of the other cytokines did not differ between the patients with and without weight loss. Our findings suggest an association between high levels of circulating TNFalpha and unexplained weight loss in Alzheimer's disease.

Neuropsychological performance in mild cognitive impairment with and without apathy.

OBJECTIVE: To investigate the neuropsychological characteristics of patients diagnosed with mild cognitive impairment (MCI) with and without apathy. METHODS: A cohort of 245 MCI patients (mean age = 72 +/- 5.5 years; mean MMSE = 27.5 +/- 1.3) was divided into two subgroups according to their Apathy Inventory score and underwent an extensive neuropsychological battery. RESULTS: There were 94 (38.4%) patients with and 151 (61.6%) patients without apathy. At baseline the apathetic subgroup had a significantly lower total score on the free and cued selective reminding test (FCSR). Furthermore, the apathetic subgroup showed a significant deterioration in FCSR total recall score between baseline and the 1-year assessment. In conclusion, the presence of apathy in MCI patients is not associated with frontal task performance but with a higher degree of memory impairment.

Hallucinations in Parkinson's disease: a follow-up study.

To study prevalence of hallucinations in patients with Parkinson's disease (PD) during a 1-year period, and identify factors predictive of the onset of hallucinations in patients who were hallucination-free at baseline, 141 unselected outpatients with PD were evaluated prospectively for a set of demographic, clinical, and therapeutic variables and the presence of hallucinations during the previous 3 months. Patient groups were compared with nonparametric tests, and logistic regression was applied to significant data. Follow-up data were available for 127 patients. The hallucination prevalence rates (%) at the first and second evaluation were, respectively, 41.7 and 49.6 for hallucinations of all types (NS), 29.1 and 40.2 for minor hallucinations (i.e., presence or passage hallucinations, and illusions) (P = 0.02), 22.8 and 21.2 for formed visual hallucinations (NS), and 8.7 and 8.7 for auditory hallucinations (NS). Hallucinations rarely started or ceased during the study. The most labile forms were minor hallucinations, which developed in 20% of patients and ceased in 9%. During follow-up, 15% of patients started to hallucinate. Three factors, all present at the first evaluation, independently predicted the onset of hallucinations in patients previously free of hallucinations at baseline (odds ratio; 95% confidence interval): severe sleep disturbances (14.3; 2.5-80.9), ocular disorders (9.1; 1.6-52.0), and a high axial motor score (5.7; 1.2-27.4). Hallucinations have a chronic course in most parkinsonian patients. Factors predicting the onset of hallucinations point to a role of extranigral brainstem involvement and a nonspecific, facilitating role of ocular disorders.

[Hippocampal sclerosis and dementia]. / Sclérose hippocampique et démences.

Hippocampal sclerosis (HS) is characterized by a severe loss of neurons and gliosis in the CA 1 sector of hippocampus. HS was found in several post mortem series of demented patients either in association with specific pathologies, such as Alzheimer disease (AD) or isolated. The symptomatology and etiology of HS remain unclear, but, in the cases of pure HS, the usual clinical diagnosis was AD. It is suggested that HS could explain unusual association of an amnestic syndrome with fronto-temporal dementia or dementia with Lewy bodies. Moreover, it could also be responsible of amnestic disorders similar to those found in AD, but remaining isolated during many years. Epilepsy or anoxia, the main causes of HS, are rarely found in the history of demented people with HS. Therefore, HS might be due to a degenerative process close to dementias lacking histologic features. Diagnosis of HS can be made during life using MRI, specially high resolution MRI or fast-spin echo relaxation time.