Marco Mauri

The brain as a target for adrenocortical steroids: Cognitive implications

It is well established that a reciprocal control exists between the brain and glucocorticoid hormones. The brain regulates adrenocortical function via hypothalamic corticotrophin releasing hormone-41 (CRH-41), glucocorticoids act at specific receptors in the hippocampus, thus promoting negative feedback mechanisms. Because the hippocampus is a major site for memory processes, a role for excessive/long-lasting plasma glucocorticoid levels has been suggested in conditions of mental impairment. Major depression, Cushings disease, and dementia of the Alzheimer type are disorders which share hyperactivity of the hypothalamo-pituitary-adrenal axis, as well as symptoms of cognitive decline. Although the mechanisms leading to hypercortisolemia appear to be different in each case, the neuropsychological features of these three disorders accord with the hypothesis of glucocorticoid-associated brain damage. It therefore is important to find pharmacological strategies that will avert or reduce these potential consequences on brain function.

Memory impairment in Cushing's disease

In the present study the cognitive performance of 25 patients with Cushings disease (CD) was extensively evaluated in comparison with normal control subjects, matched one by one. The results indicate a selective impairment of memory functions: the number of patients showing a significantly impaired mnesic performance increases with age. Moreover, the neuropsychological impairment tends to recover in those cases who underwent further controls after surgical treatment. The neuropsychological data are discussed in the light of recent evidence in the literature concerning the effects of adrenal steroids on the brain.

Memory Functioning at Menopause: Impact of Age in Ovariectomized Women

Estrogens are known to act selectively on some components of memory, exerting beneficial effects on cognitive performances. However, there are few data on the long-term effect of the lack of estrogen in postmenopausal women. Therefore, we investigated attentive and verbal memory performances in physiological and surgical menopause, drawing attention to the impact of age at menopause, and we compared a well-known aging and estrogen-dependent index, the entity of bone mass loss to memory functioning. No significant differences were found in the mean scores of attentive and psychomotor performances between physiological and surgical menopause, whereas a lower number of recalled words (recency effect = PS2) was found in surgical menopause (p < 0.001) in comparison to physiological menopause. In addition, both the age at the time of ovariectomy (r = 0.47; p = 0.014) and the years since surgery (r = –0.64; p = 0.000) correlated to short-term verbal memory performance (PS2) with better scores when surgery occurred later in women’s lives. Surgical menopause is able to affect short-term verbal memory more than physiological menopause and seems to represent a critical negative event within the female brain, in particular when it occurs prematurely.

Cognitive and neuroradiological findings in congenital adrenal hyperplasia

Nineteen patients with congenital adrenal hyperplasia (CAH) aged over 16 years were given a neuropsychological evaluation; no significant differences with individually matched normal controls were detected. CAH subjects, however, revealed slightly higher IQs with respect to the expected distribution. No significant learning disabilities could be detected. Fifteen patients underwent nuclear magnetic resonance (NMR); 4 subjects showed small areas of increased signal intensity in the white matter, without prevalence of side; this finding did not correlate with clinical and cognitive characteristics. The results are discussed in the light of possible hormonal influences.

Intentional and automatic measures of specific-category effect in the semantic impairment of patients with Alzheimer's disease

The breakdown of semantic knowledge relative to living and non-living categories was studied in patients with Alzheimers disease (AD). The same living and non-living items were used in a semantic battery and in a semantic priming paradigm exploring automatic access to the semantic system. Although AD patients showed a semantic deficit on the intentional semantic battery, they demonstrated normal semantic facilitation on the priming task. In the AD group as a whole, the semantic impairment did not preferentially affect the living category either in the intentional or automatic condition. Instead, a prevalent deficit for the living category was found in three AD patients (14% of the group) on the intentional semantic tasks, but not on the automatic one. These findings support the view that the category effect may not be a generalised phenomenon in AD but may be restricted to a limited number of patients. The intentional/automatic dissociation of the semantic breakdown demonstrated by AD patients is discussed in relation to different theories regarding the organisation of semantic memory.

Cognitive abnormalities and disease progression in a selected population of asymptomatic HIV-positive subjects.

A selected population of 41 homosexual/bisexual asymptomatic HIV-positive subjects were administered neurophysiological tests to assess language, memory, attention, logic faculties and visuo-motor functions. HIV-positive subjects differed from individually matched control subjects only in certain measures of verbal memory. Longitudinal evaluation performed after 1.5 years, however, did not indicate any further development of this mild amnesic deficit. Despite the small number studied in our sample, there seems to be a trend for older subjects to be at greater risk of developing AIDS and cognitive abnormalities than younger subjects, while differences in immunological status play a significant role in disease progression.

Dopaminergic Receptors on CD4+ T Naive and Memory Lymphocytes Correlate with Motor Impairment in Patients with Parkinson’s Disease

Parkinson’s disease (PD) is characterized by loss of dopaminergic neurons in substantia nigra pars compacta, α-synuclein (α-syn)-rich intraneuronal inclusions (Lewy bodies), and microglial activation. Emerging evidence suggests that CD4+ T lymphocytes contribute to neuroinflammation in PD. Since the mainstay of PD treatment is dopaminergic substitution therapy and dopamine is an established transmitter connecting nervous and immune systems, we examined CD4+ T naive and memory lymphocytes in PD patients and in healthy subjects (HS), with specific regard to dopaminergic receptor (DR) expression. In addition, the in vitro effects of α-syn were assessed on CD4+ T naive and memory cells. Results showed extensive association between DR expression in T lymphocytes and motor dysfunction, as assessed by UPDRS Part III score. In total and CD4+ T naive cells expression of D1-like DR decrease, while in T memory cells D2-like DR increase with increasing score. In vitro, α-syn increased CD4+ T memory cells, possibly to a different extent in PD patients and in HS, and affected DR expression with cell subset-specific patterns. The present results support the involvement of peripheral adaptive immunity in PD, and may contribute to develop novel immunotherapies for PD, as well as to better use of current dopaminergic antiparkinson drugs.

Amisulpride in the treatment of behavioural disturbances among patients with moderate to severe Alzheimer's disease.

Objective –  The aim of this article was to evaluate the effects of amisulpride on the behavioural and psychiatric symptoms of patients with Alzheimers disease (AD).

Three-year neuropsychological follow-up in a selected group of HIV-infected homosexual/bisexual men

ObjectiveTo evaluate changes in cognition in a selected group of asymptomatic homosexual/bisexual men over a 3-year period. Patients and methodsSixty HIV-infected (Centers for Disease Control stage II) subjects and 60 controls (individually matched for age and years in education) were administered neuropsychological tests evaluating attention, language, memory, logic and visuo-motor abilities. None of the patients had a history of alcohol or drug abuse, and all received the baseline cognitive evaluation within 18–24 months of seroconversion. ResultsThe HIV-infected subjects differed from controls in only one of the six memory tests (P< 0.01). Follow-up evaluation after 18 and 36 months (available for 51 and 36 subjects, respectively) demonstrated a significant deterioration in visuo-motor ability (P< 0.01) only in subjects who had progressed to AIDS, without signs or symptoms of central nervous system involvement. ConclusionsThe data suggest that cognitive alterations in asymptomatic stages of HIV infection are in most subjects minor and do not develop. Percentage rates of CD4 lymphocyte decline appear to be significantly related to deterioration in visuo-motor abilities.

Hepatotoxicity after high-dose methylprednisolone for demyelinating disease.

Liver toxicity, although not mentioned among the possible adverse effects of corticosteroids, has been occasionally reported in literature. We observed 2 cases of hepatotoxicity after a high-dose methylprednisolone treatment of a demyelinating disease and evaluated the potential relationship in the light of available evidence. The first patient developed a histologically documented acute hepatitis and recovered after 3 weeks. In the second patient, a mild augmentation of liver enzymes occurred, followed by normalization in a few days. The causal relationship between hepatotoxicity and methylprednisolone treatment was deemed probable in both cases. Careful review of the literature suggests that corticosteroid-induced liver damage may be more frequent than commonly believed.