Amyloid-associated depression: a prodromal depression of Alzheimer disease?

Department of Psychiatry, Tufts-New England Medical Center, Campus Box 1007, 750 Washington St, Boston, MA 02111, USA.
Archives of general psychiatry (Impact Factor: 12.26). 05/2008; 65(5):542-50. DOI: 10.1001/archpsyc.65.5.542
Source: PubMed

ABSTRACT A high ratio of plasma amyloid-beta peptide 40 (Abeta(40)) to Abeta(42), determined by both high Abeta(40) and low Abeta(42) levels, increases the risk of Alzheimer disease. In a previous study, we reported that depression is also associated with low plasma Abeta(42) levels in the elderly population.
To characterize plasma Abeta(40):Abeta(42) ratio and cognitive function in elderly individuals with and without depression.
Cross-sectional study.
Homecare agencies.
A total of 995 homebound elderly individuals of whom 348 were defined as depressed by a Center for Epidemiological Studies Depression score of 16 or greater.
Cognitive domains of memory, language, executive, and visuospatial functions according to levels of plasma Abeta(40) and Abeta(42) peptides.
Subjects with depression had lower plasma Abeta(42) levels (median, 14.1 vs 19.2 pg/mL; P = .006) and a higher plasma Abeta(40):Abeta(42) ratio (median, 8.9 vs 6.4; P < .001) than did those without depression in the absence of cardiovascular disease and antidepressant use. The interaction between depression and plasma Abeta(40):Abeta(42) ratio was associated with lower memory score (beta = -1.9, SE = 0.7, P = .006) after adjusting for potentially confounders. Relative to those without depression, "amyloid-associated depression," defined by presence of depression and a high plasma Abeta(40):Abeta(42) ratio, was associated with greater impairment in memory, visuospatial ability, and executive function; in contrast, nonamyloid depression was not associated with memory impairment but with other cognitive disabilities.
Amyloid-associated depression may define a subtype of depression representing a prodromal manifestation of Alzheimer disease.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Amyloid beta (Aβ) levels have been associated with an increased risk of Alzheimer's disease (AD). As depression is common before the onset of AD, serum Aβ levels could be associated with depressive symptoms. The aim of this study was to investigate whether serum Aβ levels are associated with depressive symptoms and/or cognitive function in community-dwelling elderly individuals.
    Neuropsychiatric Disease and Treatment 01/2014; 10:1621-7. · 2.00 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Late-life depression even in subsyndromal stages is strongly associated with Alzheimer's disease (AD). Furthermore, brain amyloidosis is an early biomarker in subjects who subsequently suffer from AD and can be sensitively detected by amyloid PET. Therefore, we aimed to compare amyloid load and glucose metabolism in subsyndromally depressed subjects with mild cognitive impairment (MCI). [(18)F]AV45 PET, [(18)F]FDG PET and MRI were performed in 371 MCI subjects from the Alzheimer's Disease Neuroimaging Initiative Subjects were judged β-amyloid-positive (Aβ+; 206 patients) or β-amyloid-negative (Aβ-; 165 patients) according to [(18)F]AV45 PET. Depressive symptoms were assessed by the Neuropsychiatric Inventory Questionnaire depression item 4. Subjects with depressive symptoms (65 Aβ+, 41 Aβ-) were compared with their nondepressed counterparts. Conversion rates to AD were analysed (mean follow-up time 21.5 ± 9.1 months) with regard to coexisting depressive symptoms and brain amyloid load. Aβ+ depressed subjects showed large clusters with a higher amyloid load in the frontotemporal and insular cortices (p < 0.001) with coincident hypermetabolism (p < 0.001) in the frontal cortices than nondepressed subjects. Faster progression to AD was observed in subjects with depressive symptoms (p < 0.005) and in Aβ+ subjects (p < 0.001). Coincident depressive symptoms additionally shortened the conversion time in all Aβ+ subjects (p < 0.005) and to a greater extent in those with a high amyloid load (p < 0.001). Our results clearly indicate that Aβ+ MCI subjects with depressive symptoms have an elevated amyloid load together with relative hypermetabolism of connected brain areas compared with cognitively matched nondepressed individuals. MCI subjects with high amyloid load and coexistent depressive symptoms are at high risk of faster conversion to AD.
    European journal of nuclear medicine and molecular imaging 01/2015; · 5.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Affective disorders are associated with an increased occurrence of cognitive deficits and have been linked to cognitive impairment and Alzheimer׳s disease. The putative molecular mechanisms involved in these associations are however not clear. The aim of this systematic review was to explore clinically founded evidence for amyloid-β peptides in cerebrospinal fluid and blood as putative biomarkers for affective disorders.
    Journal of Affective Disorders 07/2014; 168C:167-183. · 3.71 Impact Factor


Available from