%0 Journal Article %J J Alzheimers Dis %D 2017 %T Inflammation, Amyloid, and Atrophy in The Aging Brain: Relationships with Longitudinal Changes in Cognition. %A Sala-Llonch, Roser %A Idland, Ane-Victoria %A Borza, Tom %A Watne, Leiv Otto %A Wyller, Torgeir Bruun %A Brækhus, Anne %A Zetterberg, Henrik %A Blennow, Kaj %A Walhovd, Kristine Beate %A Fjell, Anders Martin %X

Amyloid deposition occurs in aging, even in individuals free from cognitive symptoms, and is often interpreted as preclinical Alzheimer's disease (AD) pathophysiology. YKL-40 is a marker of neuroinflammation, being increased in AD, and hypothesized to interact with amyloid-β (Aβ) in causing cognitive decline early in the cascade of AD pathophysiology. Whether and how Aβ and YKL-40 affect brain and cognitive changes in cognitively healthy older adults is still unknown. We studied 89 participants (mean age: 73.1 years) with cerebrospinal fluid samples at baseline, and both MRI and cognitive assessments from two time-points separated by two years. We tested how baseline levels of Aβ42 and YKL-40 correlated with changes in cortical thickness and cognition. Thickness change correlated with Aβ42 only in Aβ42+ participants (<600 pg/mL, n = 27) in the left motor and premotor cortices. Aβ42 was unrelated to cognitive change. Increased YKL-40 was associated with less preservation of scores on the animal naming test in the total sample (r = -0.28, p = 0.012) and less preservation of a score reflecting global cognitive function for Aβ42+ participants (r = -0.58, p = 0.004). Our results suggest a role for inflammation in brain atrophy and cognitive changes in cognitively normal older adults, which partly depended on Aβ accumulation.

%B J Alzheimers Dis %V 58 %P 829-840 %8 2017 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/28505968?dopt=Abstract %R 10.3233/JAD-161146 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Preclinical Amyloid-β and Axonal Degeneration Pathology in Delirium. %A Idland, Ane-Victoria %A Wyller, Torgeir Bruun %A Støen, Randi %A Eri, Lars Magne %A Frihagen, Frede %A Ræder, Johan %A Chaudhry, Farrukh Abbas %A Hansson, Oskar %A Zetterberg, Henrik %A Blennow, Kaj %A Bogdanovic, Nenad %A Brækhus, Anne %A Watne, Leiv Otto %X

BACKGROUND: The clinical relevance of brain β-amyloidosis in older adults without dementia is not established. As delirium and dementia are strongly related, studies on patients with delirium may give pathophysiological clues.

OBJECTIVE: To determine whether the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau) are associated with delirium in hip fracture patients with and without dementia.

METHODS: CSF was collected in conjunction to spinal anesthesia in 129 patients. Delirium was assessed using the Confusion Assessment Method once daily in all patients, both pre- and postoperatively. The diagnosis of dementia at admission was based upon clinical consensus. CSF levels of Aβ42, T-tau, and P-tau were analyzed.

RESULTS: In patients without dementia, we found lower CSF Aβ42 levels (median, 310 ng/L versus 489 ng/L, p = 0.006), higher T-tau levels (median, 505 ng/L versus 351 ng/L, p = 0.02), but no change in P-tau in patients who developed delirium (n = 16) compared to those who remained lucid (n = 49). Delirious patients also had lower ratios of Aβ42 to T-tau (p < 0.001) and P-tau (p = 0.001) relative to those without delirium. CSF Aβ42 and T-tau remained significantly associated with delirium status in adjusted analyses. In patients with dementia, CSF biomarker levels did not differ between those with (n = 54) and without delirium (n = 10).

CONCLUSION: The reduction in CSF Aβ42, indicating β-amyloidosis, and increase in T-tau, indicating neurodegeneration, in hip fracture patients without dementia developing delirium indicates that preclinical AD brain pathology is clinically relevant and possibly plays a role in delirium pathophysiology.

%B J Alzheimers Dis %V 55 %P 371-379 %8 2017 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/27662296?dopt=Abstract %R 10.3233/JAD-160461