14 Vascular risk factors for depression and apathy Research into biological aging processes promoted a further differentiation of late-life depression syndromes, and provided information about the biomarkers with which they can be distinguished 18 (see Table1). The depression-executive dysfunction subtype of late-life depression is the only subtype that has been related to vascular risk and vascular disease and a higher risk of dementia 19. In clinical practice and compared to depressed older adults without executive deficits, those with the depression-executive dysfunction syndrome more often present with reduced fluency, impaired visual naming, paranoia, loss of interest in activities, and psychomotor retardation but with a milder vegetative syndrome 20. Moreover, treatment response is lower and the rate of recurrence is higher. Still, comprising antidepressants, ECT and/or psychotherapy, in essence treatment regimens for this subtype do not differ from those prescribed for a general depressive disorder 5. Moreover, since a distinct clinical syndrome and a causal relationship between CSVD and depression could not be established, the name ‘vascular depression’ was abandoned by most researchers and clinicians 21 22. Table 1. Biomarkers and behavior associated with late-life depression subtypes Aging process Biomarkers Typical Phenotype Cerebral small vessel disease (CSVD) Systolic blood pressure Pulse wave velocity Vessel calcification White matter hyperintensities (WMH) Fractional anisotropy in fronto-striatal tracts Depressive-executive dysfunction Inflammation and dopamine depletion Interleukin-6 (IL-6) Tumor necrosis factor alpha (TNF-alpha) C-reactive protein Dopamine D1/D2 receptor density Dopamine transporter (DAT) activity Response to stimulation Inflammation, slowness Oxidative stress and mitochondrial aging F2 isoprostanes VO2 max Enzymatic activity IH MRS lactate IH MRS N-acetyl aspartate 31P MRS phosphocreatine Frailty, fatigue Adapted from: [18] Rutherford BR, Taylor WD, Brown PJ, Sneed JR, Roose SP. Biological Aging and the Future of Geriatric Psychiatry. J Gerontol A Biol Sci Med Sci 2017; 72:343–52. https://doi.org/10.1093/GERONA/GLW241. Although the association between WMH (as biomarkers for CSVD) and depression was confirmed in a meta-analysis 16, WMH are particularly related to those items of depression scales that gauge motivational problems such as loss of interest and psychomotor
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