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The association between frontal lobe perfusion and depressive symptoms in later life

  • Robert Briggs (a1), Daniel Carey (a2), Paul Claffey (a3), Triona McNicholas (a4), Louise Newman (a5), Hugh Nolan (a5), Sean P. Kennelly (a6) and Rose Anne Kenny (a7)...



Deficits in frontal lobe perfusion have been demonstrated in late-life depression; however, studies to date have generally involved small numbers, used neuroimaging rather than bedside testing and have not controlled for important covariates.


We aimed to examine the association between depressive symptoms and frontal lobe perfusion during standing, in a large cohort of community-dwelling older people.


Participants aged ≥50 years underwent continuous measurement of orthostatic blood pressure by finometry, and frontal lobe perfusion by near-infrared spectroscopy. Depressive symptoms were assessed by the eight-item Centre for Epidemiological Studies Depression Scale. Real-time frontal lobe cerebral oxygenation was measured by the Portalite System, detecting changes in frontal lobe perfusion and reporting a tissue saturation index score.


Almost 8% (209 out of 2616) had clinically significant depressive symptoms. Multilevel models demonstrated a significantly lower tissue saturation index in participants with depressive symptoms at both 60 and 90 s post-stand, with coefficients of −0.43 (95% CI −0.63 to −0.22) and −0.37 (95% CI −0.57 to −0.16), respectively. Controlling for relevant covariates did not significantly attenuate these associations. After addition of systolic blood pressure this association was no longer significant, suggesting lower blood pressure may modify this relationship.


This study demonstrates that lower frontal lobe perfusion, related to lower values of baseline systolic blood pressure, is associated with clinically significant depressive symptoms in a cohort of community-dwelling older people. Given the recognised longitudinal association between lower blood pressure and depression in older people, this may represent a potential therapeutic target for prevention of incident depression.

Declaration of interest



Corresponding author

Correspondence: Robert Briggs, The Irish Longitudinal Study on Ageing (TILDA), Mercer's Institute for Successful Ageing, St James's Hospital, James's Street, Dublin 8, Ireland. Email:


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1Taylor, WD, Aizenstein, HJ, Alexopoulos, GS. The vascular depression hypothesis: mechanisms linking vascular disease with depression. Mol Psychiatry 2013; 18(9): 963–74.
2Alexopoulos, GS. Frontostriatal and limbic dysfunction in late-life depression. Am J Geriatr Psychiatry 2002; 10(6): 687–95.
3Almeida, OP, Burton, EJ, Ferrier, N, McKeith, IG, O'Brien, JT. Depression with late onset is associated with right frontal lobe atrophy. Psychol Med 2003; 33(4): 675–81.
4Dotson, VM, Davatzikos, C, Kraut, MA, Resnick, SM. Depressive symptoms and brain volumes in older adults: a longitudinal magnetic resonance imaging study. J Psychiatry Neurosci 2009; 34(5): 367–75.
5MacFall, JR, Payne, ME, Provenzale, JE, Krishnan, KR. Medial orbital frontal lesions in late-onset depression. Biol Psychiatry 2001; 49(9): 803–6.
6Herrmann, LL, Le Masurier, M, Ebmeier, KP. White matter hyperintensities in late life depression: a systematic review. J Neurol Neurosurg Psychiatry 2008; 79(6): 619–24.
7Nobuhara, K, Okugawa, G, Sugimoto, T, Minami, T, Tamagaki, C, Takase, K, et al. Frontal white matter anisotropy and symptom severity of late-life depression: a magnetic resonance diffusion tensor imaging study. J Neurol Neurosurg Psychiatry 2006; 77(1): 120–2.
8Kumar, A, Thomas, A, Lavretsky, H, Yue, K, Huda, A, Curran, J, et al. Frontal white matter biochemical abnormalities in late-life major depression detected with proton magnetic resonance spectroscopy. Am J Psychiatry 2002; 159(4): 630–6.
9Lai, T, Payne, ME, Byrum, CE, Steffens, DC, Krishnan, KR. Reduction of orbital frontal cortex volume in geriatric depression. Biol Psychiatry 2000; 48(10): 971–5.
10Hoffmann, M. The human frontal lobes and frontal network systems: an evolutionary, clinical, and treatment perspective. ISRN Neurol 2013; 2013: 892459.10.1155/2013/892459
11Briggs, R, Kenny, RA, Kennelly, SP. Does baseline hypotension predict incident depression in a cohort of community-dwelling older people? Data from The Irish Longitudinal Study on Ageing (TILDA). Age Ageing 2017; 46(4): 648–53.
12Briggs, R, Carey, D, Kennelly, SP, Kenny, RA. Longitudinal association between orthostatic hypotension at 30 seconds post standing and late life depression. Hypertension 2018; 71(5): 946–54.10.1161/HYPERTENSIONAHA.117.10542
13Navarro, V, Gastó, C, Lomeña, F, Mateos, JJ, Marcos, T. Frontal cerebral perfusion dysfunction in elderly late-onset major depression assessed by 99MTC-HMPAO SPECT. NeuroImage 2001; 14(1 Pt 1): 202–5.10.1006/nimg.2001.0787
14Lesser, IM, Mena, I, Boone, KB, Miller, BL, Mehringer, CM, Wohl, M. Reduction of cerebral blood flow in older depressed patients. Arch Gen Psychiatry 1994; 51(9): 677–86.
15Alosco, ML, Spitznagel, MBB, Cohen, R, Raz, N, Sweet, LH, Josephson, R, et al. Reduced cerebral perfusion predicts greater depressive symptoms and cognitive dysfunction at a 1-year follow-up in patients with heart failure. Int J Geriatr Psychiatry 2014; 29(4): 428–36.
16Strangman, G, Boas, DA, Sutton, JP. Non-invasive neuroimaging using near-infrared light. Biol Psychiatry 2002; 52(7): 679–93.
17Taussky, P, O'Neal, B, Daugherty, WP, Luke, S, Thorpe, D, Pooley, RA, et al. Validation of frontal near-infrared spectroscopy as noninvasive bedside monitoring for regional cerebral blood flow in brain-injured patients. Neurosurg Focus 2012; 32(2): E2.
18Whelan, BJ, Savva, GM. Design and methodology of the Irish Longitudinal Study on Ageing. J Am Geriatr Soc 2013; 61(Suppl 2): S2658.10.1111/jgs.12199
19Nieuwhof, F, Reelick, MF, Maidan, I, Mirelman, A, Hausdorff, JM, Olde Rikkert, MGM, et al. Measuring prefrontal cortical activity during dual task walking in patients with Parkinson's disease: feasibility of using a new portable fNIRS device. Pilot Feasibility Stud 2016; 2: 59.10.1186/s40814-016-0099-2
20Bale, G, Elwell, CE, Tachtsidis, I. From Jöbsis to the present day: a review of clinical near-infrared spectroscopy measurements of cerebral cytochrome-c-oxidase. J Biomed Opt 2016; 21(9): 091307.10.1117/1.JBO.21.9.091307
21Colier, WN, Binkhorst, RA, Hopman, MT, Oeseburg, B. Cerebral and circulatory haemodynamics before vasovagal syncope induced by orthostatic stress. Clin Physiol 1997; 17(1): 8394.
22Jones, S, Chiesa, ST, Chaturvedi, N, Hughes, AD. Recent developments in near-infrared spectroscopy (NIRS) for the assessment of local skeletal muscle microvascular function and capacity to utilise oxygen. Artery Res 2016; 16: 2533.
23Finucane, C, O'Connell, MD, Fan, CWW, Savva, GM, Soraghan, CJ, Nolan, H, et al. Age-related normative changes in phasic orthostatic blood pressure in a large population study: findings from The Irish Longitudinal Study on Ageing (TILDA). Circulation 2014; 130(20): 1780–9.
24Freeman, R, Wieling, W, Axelrod, FB, Benditt, DG, Benarroch, E, Biaggioni, I, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 2011; 21(2): 6972.
25Briggs, R, Carey, D, O'Halloran, A, Kenny, RA, Kennelly, SP. Validation of the 8-item Centre for Epidemiological Studies Depression Scale in a cohort of community-dwelling older people: data from The Irish Longitudinal Study on Ageing (TILDA). Eur Geriatr Med 2018; 9: 121126.
26O'Halloran AM, K, King-Kallimanis BL, RA. The latent factors of depression from the short forms of the CES-D are consistent, reliable and valid in community-living older adults. Eur Geriatr Med 2014; 5(2): 97102.10.1016/j.eurger.2013.12.004
27Bachus, E, Holm, H, Hamrefors, V, Melander, O, Sutton, R, Magnusson, M, et al. Monitoring of cerebral oximetry during head-up tilt test in adults with history of syncope and orthostatic intolerance. Europace 2018; 20(9): 1535–42.
28Rosenbaum, D, Hagen, K, Deppermann, S, Kroczek, AM, Haeussinger, FB, Heinzel, S, et al. State-dependent altered connectivity in late-life depression: a functional near-infrared spectroscopy study. Neurobiolf Aging 2016; 39: 5768.10.1016/j.neurobiolaging.2015.11.022
29Ma, X-Y, Wang, Y-J, Xu, B, Feng, K, Sun, GX, Zhang, XQ, et al. Near-infrared spectroscopy reveals abnormal hemodynamics in the left dorsolateral prefrontal cortex of menopausal depression patients. Dis Markers 2017; 2017: 1695930.
30Abi Zeid Daou, M, Boyd, BD, Donahue, MJ, Albert, K, Taylor, WD. Frontocingulate cerebral blood flow and cerebrovascular reactivity associated with antidepressant response in late-life depression. J Affect Disord 2017; 215: 103–10.
31Navarro, V, Gastó, C, Lomeña, F, Torres, X, Mateos, JJ, Portella, MJ, et al. Prognostic value of frontal functional neuroimaging in late-onset severe major depression. Br J Psychiatry 2004; 184(4): 306–11.
32Brickman, AM, Zahra, A, Muraskin, J, Steffener, J, Holland, CM, Habeck, C, et al. Reduction in cerebral blood flow in areas appearing as white matter hyperintensities on magnetic resonance imaging. Psychiatry Res 2009; 172(2): 117–20.
33Briggs, R, Kennelly, SP, Kenny, RAA. Does baseline depression increase the risk of unexplained and accidental falls in a cohort of community-dwelling older people? Data from The Irish Longitudinal Study on Ageing (TILDA). Int J Geriatr Psychiatry 2018; 33(2): e20511.
34Mozolic, JL, Hayasaka, S, Laurienti, PJ. A cognitive training intervention increases resting cerebral blood flow in healthy older adults. Front Hum Neurosci 2010; 4: 16.
35Penninx, BW, Rejeski, WJ, Pandya, J, Miller, ME, Di Bari, M, Applegate, WB, et al. Exercise and depressive symptoms: a comparison of aerobic and resistance exercise effects on emotional and physical function in older persons with high and low depressive symptomatology. J Gerontol B Psychol Sci Soc Sci 2002; 57(2): P124–32.


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The association between frontal lobe perfusion and depressive symptoms in later life

  • Robert Briggs (a1), Daniel Carey (a2), Paul Claffey (a3), Triona McNicholas (a4), Louise Newman (a5), Hugh Nolan (a5), Sean P. Kennelly (a6) and Rose Anne Kenny (a7)...
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