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

Abstract

BackgroundThe 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.MethodsFifty-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.ResultsForty-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.ConclusionIn 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.

Dual-Task Performance and Neurodegeneration: Correlations Between Timed Up-and-Go Dual-Task Test Outcomes and Alzheimer’s Disease Cerebrospinal Fluid Biomarkers

“…Contraindications for performing lumbar puncture were anticoagulant treatment or signs of increased intracranial pressure. Since the AD biomarker profile becomes less informative in older individuals [47], lumbar puncture is generally not performed in patients of advanced age. Moreover, in individuals who are severely overweight, lumbar puncture is not carried out because of technical difficulties.…”

Improved Differential Diagnosis of Alzheimer’s Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers

“…The control subjects were recruited by advertising in the local newspaper and were considered cognitively unimpaired, based on their history and a Mini-Mental State Examination (MMSE) test. Approximately half of the controls consisted of 87–89-year-old men from the ULSAM cohort, individuals who have been followed since the early 1970 s [13].…”

CSF biomarkers in patients with epilepsy in Alzheimer’s disease: a nation-wide study

“…This may be due to increased prevalence of subclinical Alzheimer’s disease pathology in older age groups, making Alzheimer’s disease biomarker results overall less informative in the elderly. 25 , 26 …”