In Brief Neuropsychological Assessment, Amnestic Mild Cognitive Impairment (MCI) Is associated with Cerebrospinal Fluid Biomarkers for Cognitive Decline in Contrast to the Prevailing NIA-AA MCI Criterion.

BACKGROUND: In the care of persons with cognitive problems, it is important to use a valid mild cognitive impairment (MCI) criterion that discriminates well between normal and pathological aging. OBJECTIVE: To find the brief neuropsychological screening criterion that best correlates with cerebrospinal fluid (CSF) biomarkers for cognitive decline and dementia in persons seeking help for cognitive problems. METHODS: 452 consecutively recruited patients (age 40-80 years) from memory-clinics in the Norwegian national multicentre longitudinal study Dementia Disease Initiation were included. CSF data as well as full data from brief neuropsychological screening were available for all patients. RESULTS: Amnestic MCI, including at least one memory test below T-score 40, outperformed the conventional US National Institute on Aging-Alzheimer's Association (NIA-AA) MCI criterion. Only amnestic MCI was significantly associated with biomarker pattern of NIA-AA stage 2 (low CSF Aß42 concentrations and elevated tau) in multivariate regression analysis. CONCLUSIONS: The finding that amnestic MCI based on brief neuropsychological assessment is significantly associated with CSF biomarkers for cognitive decline and Alzheimer's disease is in accordance with longitudinal studies that find memory impairment; both in itself and especially in combination with other cognitive deficit to constitute a risk factor for subsequent cognitive decline and dementia. The prevalence of pathological biomarkers for Alzheimer's disease is common in the elderly and the clinical significance of present findings depend on longitudinal validation.

Detecting At-Risk Alzheimer's Disease Cases.

While APOEɛ4 is the major genetic risk factor for Alzheimer's disease (AD), amyloid dysmetabolism is an initial or early event predicting clinical disease and is an important focus for secondary intervention trials. To improve identification of cases with increased AD risk, we evaluated recruitment procedures using pathological CSF concentrations of Aß42 (pAß) and APOEɛ4 as risk markers in a multi-center study in Norway. In total, 490 subjects aged 40-80 y were included after response to advertisements and media coverage or memory clinics referrals. Controls (n = 164) were classified as normal controls without first-degree relatives with dementia (NC), normal controls with first-degree relatives with dementia (NCFD), or controls scoring below norms on cognitive screening. Patients (n = 301) were classified as subjective cognitive decline or mild cognitive impairment. Subjects underwent a clinical and cognitive examination and MRI according to standardized protocols. Core biomarkers in CSF from 411 and APOE genotype from 445 subjects were obtained. Cases (both self-referrals (n = 180) and memory clinics referrals (n = 87)) had increased fractions of pAß and APOEɛ4 frequency compared to NC. Also, NCFD had higher APOEɛ4 frequencies without increased fraction of pAß compared to NC, and cases recruited from memory clinics had higher fractions of pAß and APOEɛ4 frequency than self-referred. This study shows that memory clinic referrals are pAß enriched, whereas self-referred and NCFD cases more frequently are pAß negative but at risk (APOEɛ4 positive), suitable for primary intervention.

Convergent Results from Neuropsychology and from Neuroimaging in Patients with Mild Cognitive Impairment.

BACKGROUND/AIMS: To investigate the correspondence between neuropsychological single measures and variation in fludeoxyglucose positron emission tomography (FDG PET) glucose metabolism and magnetic resonance imaging (MRI) cortical thickness in mild cognitive impairment (MCI) patients. METHODS: Forty-two elderly controls and 73 MCI subjects underwent FDG PET and MRI scanning. Backward regression analyses with PET and MRI regions were used as dependent variables, while Rey Auditory Verbal Memory Test (RAVLT) recall, Trail Making Test B (TMT B), and a composite test score (RAVLT learning and immediate recall, TMT A, COWAT, and letter-number sequencing) were used as predictor variables. RESULTS: The composite score predicted variation in cortical metabolism; supplementary analyses showed that TMT B was significantly correlated with PET metabolism as well. RAVLT and TMT B were significant predictors of variation in MRI cortical thickness. CONCLUSION: Our results indicate that RAVLT and TMT B are sensitive to variation in Alzheimer disease neuroimaging markers.

Neuropsychological Profiles in Mild Cognitive Impairment due to Alzheimer's and Parkinson's Diseases.

BACKGROUND: Neuropsychological comparisons between patients with mild cognitive impairment due to Parkinson's disease (MCI-PD) and Alzheimer's disease (MCI-AD) is mostly based on indirect comparison of patients with these disorders and normal controls (NC). OBJECTIVE: The focus of this study was to make a direct comparison between patients with these diseases. METHODS: The study compared 13 patients with MCI-PD and 19 patients with MCI-AD with similar age, education and gender. The participants were recruited and assessed at the same university clinic with equal methods. RESULTS: The main finding was that on group level, MCI-AD scored significantly poorer on learning and memory tests than MCI-PD, whereas MCI-PD were impaired on 1 of 3 measures of executive functioning. CONCLUSION: MCI-AD performed poorer learning and memory tests, whereas MCI-PD only scored below the employed cut-off on one single executive test. In general, MCI-PD was noticeably less cognitively impaired than MCI-AD.

Hippocampal Subfield Atrophy in Multi-Domain but Not Amnestic Mild Cognitive Impairment.

BACKGROUND/AIMS: To investigate differences in hippocampal (HP) subfields and the adjoining perirhinal and entorhinal cortices (PRC and ERC) between amnestic mild cognitive impairment (aMCI) and multi-domain amnestic MCI (mdMCI) patients, and controls. METHODS: Nineteen patients characterized as aMCI were compared with 24 mdMCI patients and 31 controls by means of an automatic HP segmentation procedure. RESULTS: We found significant atrophy of the PRC and ERC in aMCI relative to controls, whereas a more pronounced pattern of atrophy in most subfields, including total HP volume, was found in the mdMCI group. The mdMCI group also had a significant cornu ammonis sector 4 region with dentate gyrus, subiculum and total HP atrophy relative to aMCI. CONCLUSION: The aMCI group showed atrophy in the PRC and ERC, whereas significantly more affection of the HP subfields was evident in mdMCI. The mdMCI group may thus represent clinical progression relative to aMCI coupled with HP subfield affection.