Long-Term Cognitive Impairments and Attentional Deficits in Patients with Cushing's Disease and Cortisol-Producing Adrenal Adenoma in Remission
Context: Cognitive function is impaired in patients with active Cushing's syndrome (CS). Objective: The aim was to study cognitive function in patients with CS in long-term remission. Design: We conducted a cross-sectional, case-controlled, single center study. Patients: Fifty-five patients previously treated for Cushing's disease (n = 43) and cortisol-producing adrenal adenoma (n = 12) and 55 controls matched for age, gender, and educational level participated in the study. Methods: Working memory, attention, information-processing speed, verbal fluency, and reading speed were studied using standardized neuropsychological testing and alerting, orienting, and executive control using the Attentional Network Test. Fatigue impact scale and the comprehensive psychopathological rating scale were used to evaluate fatigue and affective disorder. Results: Median (interquartile range) duration of remission was 13 (5-19) yr and the mean ± sd age at follow-up was 54 ± 14 yr. Compared to controls, patients had a higher score on the fatigue impact scale, indicating greater burdens of fatigue, and a higher score on the comprehensive psychopathological rating scale subscales for depression and anxiety. In a multivariate analysis, attention, spatial orienting, alerting, working memory, verbal fluency, and reading speed were all diminished in comparison to controls, independent of scores for affective disorder and fatigue. No overall difference in outcome was seen between patients in long-term remission for Cushing's disease and cortisol-producing adrenal adenoma. Conclusion: Patients with CS in remission have impaired cognitive function that cannot be explained by the coexistence of affective disorder or chronic fatigue. The pattern of cognitive and attentional deficits suggests a more global involvement of the brain function than has previously been suggested.
Available from: Joe Herbert
- "cortisol in humans) can either damage the brain directly (Uno et al., 1994; Sapolsky et al., 1990) or potentiate the action of other damaging agents, including b-amyloid (Magarinos et al., 1996, 1998; Sapolsky, 1996; Goodman et al., 1996; Tombaugh et al., 1992), whereas blockade of GCs is protective. For example, the hypercortisolism of Cushing's disease decreases hippocampal and frontal lobe volume (Starkman, 2013; Starkman et al., 1992) and results in long-term reductions in white matter and impaired cognitive function long after remission (van der Werff et al., 2014; Ragnarsson et al., 2012). A reduction in hippocampal volume is has been repeatedly reported in MDD, but considerable variation exists in the literature. "
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ABSTRACT: Depression (MDD) is prodromal to, and a component of, Alzheimer’s disease (AD): it may also be a trigger for incipient AD. MDD is not a unitary disorder, so there may be particular subtypes of early life MDD that pose independent high risks for later AD, though the identification of these subtypes is problematical. There may either be a common pathological event underlying both MDD and AD, or MDD may sensitize the brain to a second event (‘hit’) that precipitates AD. MDD may also accelerate brain ageing, including altered DNA methylation, increased cortisol but decreasing DHEA and thus the risk for AD. So far, genes predicting AD (e.g. APOEε4) are not risk factors for MDD, and those implicated in MDD (e.g. SLC6A4) are not risks for AD, so a common genetic predisposition looks unlikely. There is as yet no strong indication that an epigenetic event occurs during some forms of MDD that predisposes to later AD, though the evidence is limited.
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ABSTRACT: The case of a 85 years old woman is reported. She suffered from a partially reversible episodic memory dysfunction after i.m. injections of bethamethasone for acute lumbalgia. Cognitive impairments observed in Cushing's disease are reviewed as well as the deleterious effects of glucocorticoid treatments on episodic memory. They could be prevented by memantine.
Available from: Per Mårten Johansson
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ABSTRACT: Hormones like insulin-like growth factor-I (IGF-I), thyroid hormones, and sex
steroids decrease with normal aging. It is, however, unclear whether low hormone
levels are related to age-related conditions such as Alzheimer’s disease (AD) or
whether hormone levels are associated with markers of aging like leukocyte telomere
length (LTL). The aims of this thesis were to validate cerebrospinal fluid (CSF)
biomarkers in AD and to investigate whether hormonal aberrations might contribute
to reduced cognitive function.
Consecutive patients undergoing primary evaluation of cognitive impairment (n=60)
and healthy controls (n=20) were included. The patients had AD dementia or mild
cognitive impairment (MCI) that was later diagnosed as AD dementia upon follow-
up (n=32), stable MCI (SMCI, n=13), or other dementias (n=15). The same physician
examined all subjects. Serum and CSF samples were collected and LTL was analyzed
using quantitative PCR technique.
In Paper I, the core AD biomarkers in CSF (amyloid β [Aβ]1-42, total-tau [T-tau], and
phosphorylated tau protein [P-tau]) demonstrated a very high ability to diagnose AD
compared to combined groups of controls and SMCI (area under the receiver
operating characteristic curve [AUROC]=0.97 [95% CI 0.93–1.00, P<0.0001]). The
addition of other biomarkers only marginally increased the diagnostic accuracy. In
Paper II, serum IGF-I was higher in patients with AD or other dementias compared
to healthy controls (P=0.01 and P<0.05, respectively), whereas CSF IGF-I remained
unchanged. In Paper III, AD patients showed marginally increased serum thyroid-
stimulating hormone (TSH). CSF total thyroxine (T4) level was lower both in
patients with AD and other dementias compared to controls (both P=0.001). In
Paper IV, both male and female patients showed increased serum concentrations of
estrone (E1) and estrone sulfate (E1S) compared to controls of similar gender, but
serum levels of other precursor sex steroids and cortisol were increased only in female
patients. In Paper V, SMCI patients showed reduced LTL compared to AD patients
(p=0.02) and controls (p=0.008).
In conclusion, the CSF biomarkers Aβ1-42, T-tau, and P-tau were highly accurate to
diagnose AD in a well-defined study population. There were multiple alterations in
hormonal levels in AD. There might be reduced passage of IGF-I and thyroxine
through the blood brain barrier and aberrations in sex steroids and cortisol were more
apparent in female patients. Low LTL might indicate more marked biological aging in
SMCI patients whereas low LTL does not appear to be a risk factor for conversion to
Keywords: hormones, aging, cerebrospinal, Alzheimer
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