Skip to main content
Top
Published in: BMC Geriatrics 1/2017

Open Access 01-12-2017 | Research Article

Cognitive function in very old men does not correlate to biomarkers of Alzheimer’s disease

Authors: V. Velickaite, V. Giedraitis, K. Ström, I. Alafuzoff, H. Zetterberg, L. Lannfelt, L. Kilander, E-M. Larsson, M. Ingelsson

Published in: BMC Geriatrics | Issue 1/2017

Login to get access

Abstract

Background

The Alzheimer’s disease (AD) brain displays atrophy with amyloid-β (Aβ) and tau deposition, whereas decreased Aβ42 and increased tau are measured in cerebrospinal fluid (CSF). The aim of this study was to relate cognitive performance to the degree of brain atrophy, CSF biomarker levels and neuropathology in a cohort of aged men.

Methods

Fifty-eight 86–92-year-old men from the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort underwent cognitive testing, brain computed tomography and lumbar puncture. Atrophy was graded with established scales. Concentrations of CSF Aβ42, t-tau and p-tau were measured by ELISA. Thirteen brains were examined post mortem.

Results

Forty-six of the individuals were considered non-demented, whereas twelve were diagnosed with dementia, either at baseline (n = 4) or during follow-up (n = 8). When comparing subjects with and without dementia, there were no differences in the degree of atrophy, although the mini mental state examination (MMSE) scoring correlated weakly with the degree of medial temporal atrophy (MTA) (p = 0.04). Moreover, the CSF biomarker levels did not differ significantly between healthy (n = 27) and demented (n = 8) subjects (median values 715 vs 472 pg/ml for Aβ42, 414 vs 427 pg/ml for t-tau and 63 vs 60 pg/ml for p-tau). Similarly, there were no differences in the biomarker levels between individuals with mild (n = 24) and severe (n = 11) MTA (median values 643 vs 715 pg/ml for Aβ42, 441 vs 401 pg/ml for t-tau and 64 vs 53 pg/ml for p-tau). Finally, the neuropathological changes did not correlate with any of the other measures.

Conclusion

In this cohort of aged men only a weak correlation could be seen between cognitive performance and MTA, whereas the various neuroradiological, biochemical and neuropathological measures did not correlate with each other. Thus, AD biomarkers seem to be less informative in subjects of an advanced age.
Literature
1.
go back to reference Winblad B, Amouyel P, Andrieu S, Ballard C, Brayne C, Brodaty H, Cedazo-Minguez A, Dubois B, Edvardsson D, Feldman H, et al. Defeating Alzheimer's disease and other dementias: a priority for European science and society. Lancet Neurol. 2016;15:455–532. doi:10.1016/S1474-4422(16)00062-4.CrossRefPubMed Winblad B, Amouyel P, Andrieu S, Ballard C, Brayne C, Brodaty H, Cedazo-Minguez A, Dubois B, Edvardsson D, Feldman H, et al. Defeating Alzheimer's disease and other dementias: a priority for European science and society. Lancet Neurol. 2016;15:455–532. doi:10.​1016/​S1474-4422(16)00062-4.CrossRefPubMed
3.
6.
8.
go back to reference Serrano-Pozo A, Qian J, Monsell SE, Blacker D, Gomez-Isla T, Betensky RA, Growdon JH, Johnson KA, Frosch MP, Sperling RA, et al. Mild to moderate Alzheimer dementia with insufficient neuropathological changes. Ann Neurol. 2014;75:597–601. doi:10.1002/ana.24125.CrossRefPubMedPubMedCentral Serrano-Pozo A, Qian J, Monsell SE, Blacker D, Gomez-Isla T, Betensky RA, Growdon JH, Johnson KA, Frosch MP, Sperling RA, et al. Mild to moderate Alzheimer dementia with insufficient neuropathological changes. Ann Neurol. 2014;75:597–601. doi:10.​1002/​ana.​24125.CrossRefPubMedPubMedCentral
13.
go back to reference Tang Y, Whitman GT, Lopez I, Baloh RW. Brain volume changes on longitudinal magnetic resonance imaging in normal older people. J Neuroimaging. 2001;11:393–400.CrossRefPubMed Tang Y, Whitman GT, Lopez I, Baloh RW. Brain volume changes on longitudinal magnetic resonance imaging in normal older people. J Neuroimaging. 2001;11:393–400.CrossRefPubMed
14.
go back to reference Zhang Y, Qiu C, Lindberg O, Bronge L, Aspelin P, Backman L, Fratiglioni L, Wahlund LO. Acceleration of hippocampal atrophy in a non-demented elderly population: the SNAC-K study. Int Psychogeriatr. 2010;22:14–25. doi:10.1017/S1041610209991396.CrossRefPubMed Zhang Y, Qiu C, Lindberg O, Bronge L, Aspelin P, Backman L, Fratiglioni L, Wahlund LO. Acceleration of hippocampal atrophy in a non-demented elderly population: the SNAC-K study. Int Psychogeriatr. 2010;22:14–25. doi:10.​1017/​S104161020999139​6.CrossRefPubMed
15.
go back to reference Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006;5:228–34.CrossRefPubMed Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer's disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006;5:228–34.CrossRefPubMed
17.
go back to reference Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, Blennow K, Soares H, Simon A, Lewczuk P, et al. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol. 2009;65:403–13. doi:10.1002/ana.21610.CrossRefPubMedPubMedCentral Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, Blennow K, Soares H, Simon A, Lewczuk P, et al. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol. 2009;65:403–13. doi:10.​1002/​ana.​21610.CrossRefPubMedPubMedCentral
19.
go back to reference Skillback T, Farahmand BY, Rosen C, Mattsson N, Nagga K, Kilander L, Religa D, Wimo A, Winblad B, Schott JM, et al. Cerebrospinal fluid tau and amyloid-beta1-42 in patients with dementia. Brain. 2015;138:2716–31. doi:10.1093/brain/awv181.CrossRefPubMed Skillback T, Farahmand BY, Rosen C, Mattsson N, Nagga K, Kilander L, Religa D, Wimo A, Winblad B, Schott JM, et al. Cerebrospinal fluid tau and amyloid-beta1-42 in patients with dementia. Brain. 2015;138:2716–31. doi:10.​1093/​brain/​awv181.CrossRefPubMed
20.
go back to reference Ewers M, Mattsson N, Minthon L, Molinuevo JL, Antonell A, Popp J, Jessen F, Herukka SK, Soininen H, Maetzler W, et al. CSF biomarkers for the differential diagnosis of Alzheimer's disease: a large-scale international multicenter study. Alzheimers Dement. 2015;11:1306–15. doi:10.1016/j.jalz.2014.12.006.CrossRefPubMed Ewers M, Mattsson N, Minthon L, Molinuevo JL, Antonell A, Popp J, Jessen F, Herukka SK, Soininen H, Maetzler W, et al. CSF biomarkers for the differential diagnosis of Alzheimer's disease: a large-scale international multicenter study. Alzheimers Dement. 2015;11:1306–15. doi:10.​1016/​j.​jalz.​2014.​12.​006.CrossRefPubMed
21.
go back to reference Franzon K, Zethelius B, Cederholm T, Kilander L. Modifiable midlife risk factors, independent aging, and survival in older men: report on long-term follow-up of the Uppsala longitudinal study of adult men cohort. J Am Geriatr Soc. 2015;63:877–85. doi:10.1111/jgs.13352.CrossRefPubMed Franzon K, Zethelius B, Cederholm T, Kilander L. Modifiable midlife risk factors, independent aging, and survival in older men: report on long-term follow-up of the Uppsala longitudinal study of adult men cohort. J Am Geriatr Soc. 2015;63:877–85. doi:10.​1111/​jgs.​13352.CrossRefPubMed
22.
go back to reference Ronnemaa E, Zethelius B, Lannfelt L, Kilander L. Vascular risk factors and dementia: 40-year follow-up of a population-based cohort. Dement Geriatr Cogn Disord. 2011;31:460–6. doi:10.1159/000330020.CrossRefPubMed Ronnemaa E, Zethelius B, Lannfelt L, Kilander L. Vascular risk factors and dementia: 40-year follow-up of a population-based cohort. Dement Geriatr Cogn Disord. 2011;31:460–6. doi:10.​1159/​000330020.CrossRefPubMed
23.
go back to reference Syvanen AC, Sajantila A, Lukka M. Identification of individuals by analysis of biallelic DNA markers, using PCR and solid-phase minisequencing. Am J Hum Genet. 1993;52:46–59.PubMedPubMedCentral Syvanen AC, Sajantila A, Lukka M. Identification of individuals by analysis of biallelic DNA markers, using PCR and solid-phase minisequencing. Am J Hum Genet. 1993;52:46–59.PubMedPubMedCentral
24.
go back to reference Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.CrossRefPubMed Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.CrossRefPubMed
25.
go back to reference Solomon PR, Hirschoff A, Kelly B, Relin M, Brush M, DeVeaux RD, Pendlebury WW. A 7 minute neurocognitive screening battery highly sensitive to Alzheimer's disease. Arch Neurol. 1998;55:349–55.CrossRefPubMed Solomon PR, Hirschoff A, Kelly B, Relin M, Brush M, DeVeaux RD, Pendlebury WW. A 7 minute neurocognitive screening battery highly sensitive to Alzheimer's disease. Arch Neurol. 1998;55:349–55.CrossRefPubMed
26.
go back to reference Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P, Kuiper M, Steinling M, Wolters EC, Valk J. Atrophy of medial temporal lobes on MRI in "probable" Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry. 1992;55:967–72.CrossRefPubMedPubMedCentral Scheltens P, Leys D, Barkhof F, Huglo D, Weinstein HC, Vermersch P, Kuiper M, Steinling M, Wolters EC, Valk J. Atrophy of medial temporal lobes on MRI in "probable" Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry. 1992;55:967–72.CrossRefPubMedPubMedCentral
28.
go back to reference Pasquier F, Leys D, Weerts JG, Mounier-Vehier F, Barkhof F, Scheltens P. Inter- and intraobserver reproducibility of cerebral atrophy assessment on MRI scans with hemispheric infarcts. Eur Neurol. 1996;36:268–72.CrossRefPubMed Pasquier F, Leys D, Weerts JG, Mounier-Vehier F, Barkhof F, Scheltens P. Inter- and intraobserver reproducibility of cerebral atrophy assessment on MRI scans with hemispheric infarcts. Eur Neurol. 1996;36:268–72.CrossRefPubMed
29.
go back to reference Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjogren M, Wallin A, Ader H, Leys D, Pantoni L, et al. A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke. 2001;32:1318–22.CrossRefPubMed Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjogren M, Wallin A, Ader H, Leys D, Pantoni L, et al. A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke. 2001;32:1318–22.CrossRefPubMed
32.
33.
go back to reference Thal DR, Ghebremedhin E, Rub U, Yamaguchi H, Del Tredici K, Braak H. Two types of sporadic cerebral amyloid angiopathy. J Neuropathol Exp Neurol. 2002;61:282–93.CrossRefPubMed Thal DR, Ghebremedhin E, Rub U, Yamaguchi H, Del Tredici K, Braak H. Two types of sporadic cerebral amyloid angiopathy. J Neuropathol Exp Neurol. 2002;61:282–93.CrossRefPubMed
34.
go back to reference Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol. 2012;123:1–11. doi:10.1007/s00401-011-0910-3.CrossRefPubMed Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol. 2012;123:1–11. doi:10.​1007/​s00401-011-0910-3.CrossRefPubMed
35.
36.
37.
40.
go back to reference Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013;12:357–67. doi:10.1016/S1474-4422(13)70044-9.CrossRefPubMed Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, Szoeke C, Macaulay SL, Martins R, Maruff P, et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol. 2013;12:357–67. doi:10.​1016/​S1474-4422(13)70044-9.CrossRefPubMed
41.
Metadata
Title
Cognitive function in very old men does not correlate to biomarkers of Alzheimer’s disease
Authors
V. Velickaite
V. Giedraitis
K. Ström
I. Alafuzoff
H. Zetterberg
L. Lannfelt
L. Kilander
E-M. Larsson
M. Ingelsson
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Geriatrics / Issue 1/2017
Electronic ISSN: 1471-2318
DOI
https://doi.org/10.1186/s12877-017-0601-6

Other articles of this Issue 1/2017

BMC Geriatrics 1/2017 Go to the issue