The effect of subsyndromal symptoms of depression and white matter lesions on disability for individuals with mild cognitive impairment.

OBJECTIVE: To assess the effect of subsyndromal symptoms of depression (SSD) on ratings of disability for individuals with mild cognitive impairment (MCI). METHODS: Data from 405 MCI participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were analyzed. Participants were evaluated at baseline and at 6-month intervals over 2 years. Severity of depressive symptoms was rated utilizing the Geriatric Depression Scale. Disability was assessed utilizing the Functional Assessment Questionnaire (FAQ). Other clinical variables included white matter lesion (WML) and intracranial brain (ICV) volumes derived from magnetic resonance imaging, ratings of overall cognitive function (Alzheimer's Disease Assessment Scale, ADAS), and apolipoprotein E (ApoE) status. Demographic variables included age, education, and gender. RESULTS: SSD individuals had a lower volume of WML and higher frequency of ApoE ε4 alleles than nondepressed participants but the two groups did not differ with respect to other clinical or demographic variables. At baseline, SSD individuals were 1.77 times more likely to have poorer FAQ scores than individuals with no symptoms of depression after controlling for the effect of cognitive functioning, ICV, WML, and ApoE status. The presence of SSD at baseline was not associated with a poorer course of disability outcomes, cognitive functioning, or conversion to dementia over 24 months. CONCLUSIONS: SSD demonstrated a significant impact on disability for MCI individuals, who are also at high risk for functional limitations related to neurodegenerative disease. Therefore, the treatment of SSD may represent a significant avenue to reduce the burden of disability in this vulnerable patient population.

Impact of apolipoprotein E4-cerebrospinal fluid ß-amyloid interaction on hippocampal volume loss over 1 year in mild cognitive impairment.

BACKGROUND: The majority of studies relating amyloid pathology with brain volumes have been cross-sectional. Apolipoprotein ɛ4 (APOE ɛ4), a genetic risk factor for Alzheimer's disease, is also known to be associated with hippocampal volume loss. No studies have considered the effects of amyloid pathology and APOE ɛ4 together on longitudinal volume loss. METHODS: We evaluated whether an abnormal level of cerebrospinal fluid beta-amyloid (CSF Aß) and APOE ɛ4 carrier status were independently associated with greater hippocampal volume loss over 1 year. We then assessed whether APOE ɛ4 status and CSF Aß acted synergistically, testing the significance of an interaction term in the regression analysis. We included 297 participants: 77 cognitively normal, 144 with mild cognitive impairment (MCI), and 76 with Alzheimer's disease. RESULTS: An abnormal CSF Aß level was found to be associated with greater hippocampal volume loss over 1 year in each group. APOE ɛ4 was associated with hippocampal volume loss only in the cognitively normal and MCI groups. APOE ɛ4 carriers with abnormal CSF Aß in the MCI group acted synergistically to produce disproportionately greater volume loss than noncarriers. CONCLUSION: Baseline CSF Aß predicts progression of hippocampal volume loss. APOE ɛ4 carrier status amplifies the degree of neurodegeneration in MCI. Understanding the effect of interactions between genetic risk and amyloid pathology will be important in clinical trials and our understanding of the disease process.