Olfactory and gustatory functioning and food preferences of patients with Alzheimer's disease and mild cognitive impairment compared to controls: the NUDAD project.

Our aim is to compare olfactory and gustatory function and food preferences of patients with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD) with controls. We included 22 patients with MCI, 30 patients with AD and 40 controls and assessed olfactory threshold, odor discrimination and odor identification (Sniffin' Sticks), gustatory functioning (Taste Strips), and food preferences (Macronutrient and Taste Preference Ranking Task). Linear regression analyses were used to study associations of five cognitive domains or AD biomarkers with olfactory functioning. Groups did not differ in olfactory threshold, gustatory function and food preferences. Patients with MCI and AD scored lower on odor discrimination and identification than controls. Poorer memory, but no other cognitive domain, was associated with poorer odor discrimination and odor identification, but not with odor threshold. No associations with AD biomarkers were found. In conclusion, patients with MCI and AD have poorer odor discrimination and identification ability than controls, but similar detection thresholds. This is likely a consequence of poorer memory rather than directly caused by AD pathology.

Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort.

OBJECTIVE: To determine how amyloid ß 42 (Aß42), total tau (t-tau), and phosphorylated tau (p-tau) levels in CSF behave in a large cohort of patients with different types of dementia. METHODS: Baseline CSF was collected from 512 patients with Alzheimer disease (AD) and 272 patients with other types of dementia (OD), 135 patients with a psychiatric disorder (PSY), and 275 patients with subjective memory complaints (SMC). Aß42, t-tau, and p-tau (at amino acid 181) were measured in CSF by ELISA. Autopsy was obtained in a subgroup of 17 patients. RESULTS: A correct classification of patients with AD (92%) and patients with OD (66%) was accomplished when CSF Aß42 and p-tau were combined. Patients with progressive supranuclear palsy had normal CSF biomarker values in 90%. Patients with Creutzfeldt-Jakob disease demonstrated an extremely high CSF t-tau at a relatively normal CSF p-tau. CSF AD biomarker profile was seen in 47% of patients with dementia with Lewy bodies (DLB), 38% in corticobasal degeneration (CBD), and almost 30% in frontotemporal lobar degeneration (FTLD) and vascular dementia (VaD). PSY and SMC patients had normal CSF biomarkers in 91% and 88%. Older patients are more likely to have a CSF AD profile. Concordance between clinical and neuropathologic diagnosis was 85%. CSF markers reflected neuropathology in 94%. CONCLUSION: CSF Aß42, t-tau, and p-tau are useful in differential dementia diagnosis. However, in DLB, FTLD, VaD, and CBD, a substantial group exhibit a CSF AD biomarker profile, which requires more autopsy confirmation in the future.

CSF biomarkers predict rate of cognitive decline in Alzheimer disease.

OBJECTIVE: CSF biomarkers amyloid beta 1-42 (Abeta(42)), total tau (tau), and tau phosphorylated at threonine 181 (p-tau-181) are useful diagnostic markers for Alzheimer disease (AD). Less is known about these biomarkers as predictors for further cognitive decline in patients with AD. We hypothesized that high tau, especially in combination with relatively low p-tau-181, is a marker of rapid decline, since it has been associated with fast neuronal degeneration. METHODS: A total of 151 patients with AD of whom we had baseline CSF were included from our memory clinic. All patients had at least 2 Mini-Mental State Examination (MMSE) scores, obtained no less than 1 year apart. Linear mixed models were used to assess associations between CSF biomarkers and the rate of cognitive decline as measured with the MMSE. CSF biomarkers were used in quintiles, random intercept and random slope with time were assumed, and the analyses were corrected for sex and age. RESULTS: The patients with AD (45% women, age 66 +/- 9 years, baseline MMSE 22 +/- 4) had a follow-up period of 2.0 (1.0-5.0) years. Linear mixed models revealed no relations between any CSF biomarker and baseline MMSE. However, CSF biomarkers did predict cognitive decline over time. A low p-tau-181/tau ratio was the strongest predictor with a dose-dependent effect (lowest vs highest quintile: 2.9 vs 1.3 MMSE points annual decline, p for trend <0.001). In addition, low Abeta(42), high tau, and high tau/Abeta(42)-ratio were associated with rapid cognitive decline (p < 0.05). CONCLUSION: At the time of diagnosis, a combination of high CSF tau without proportionally elevated p-tau-181 is associated with a faster rate of cognitive decline.

Patients with Alzheimer disease with multiple microbleeds: relation with cerebrospinal fluid biomarkers and cognition.

BACKGROUND AND PURPOSE: Microbleeds (MBs) are commonly observed in Alzheimer disease. A minority of patients has multiple MBs. We aimed to investigate associations of multiple MBs in Alzheimer disease with clinical and MRI characteristics and cerebrospinal fluid biomarkers. METHODS: Patients with Alzheimer disease with multiple (>or=8) MBs on T2*-weighted MRI were matched for age, sex, and field strength with patients with Alzheimer disease without MBs on a 1:2 basis. We included 21 patients with multiple MBs (73+/-7 years, 33% female) and 42 patients without MBs (72+/-7 years, 38% female). Mini-Mental State Examination was used to assess dementia severity. Cognitive functions were assessed using neuropsychological tests. Medial temporal lobe atrophy (0 to 4), global cortical atrophy (0 to 3), and white matter hyperintensities (0 to 30) were assessed using visual rating scales. In a subset, apolipoprotein E genotype and cerebrospinal fluid amyloid beta 1-42, total tau and tau phosphorylated at threonine 181 were determined. RESULTS: Patients with multiple MBs performed worse on Mini-Mental State Examination (multiple MB: 17+/-7; no MB: 22+/-4, P<0.05) despite similar disease duration. Atrophy was not related to presence of MBs, but patients with multiple MBs had more white matter hyperintensities (multiple MB: 8.8+/-4.8; no MB: 3.2+/-3.6, P<0.05). Adjusted for age, sex, white matter hyperintensities, and medial temporal lobe atrophy, the multiple MB group additionally performed worse on Visual Association Test object naming and animal fluency. Patients with multiple MBs had lower cerebrospinal fluid amyloid beta 1-42 levels (307+/-61) than patients without MBs (505+/-201, P<0.05). Adjusted for the same covariates, total tau, and tau phosphorylated at threonine 181 were higher in the multiple MB group. CONCLUSIONS: Microbleeds are associated with the clinical manifestation and biochemical hallmarks of Alzheimer disease, suggesting possible involvement of MBs in the pathogenesis of Alzheimer disease.