Mediterranean diet in predementia and dementia syndromes.

There is a critical need to potentially individualize new strategies able to prevent and to slow down the progression of predementia and dementia syndromes. Only recently higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline although the Mediterranean diet (MeDi) combines several foods, micro- and macronutrients already separately proposed as potential protective factors against dementia and predementia syndromes. In fact, elevated saturated fatty acids could have negative effects on age-related cognitive decline and mild cognitive impairment (MCI). Furthermore, at present, epidemiological evidence suggested a possible association among fish consumption, monounsaturated fatty acids and polyunsaturated fatty acids (PUFA) (particularly, n-3 PUFA) and reduced risk of cognitive decline and dementia. Light to moderate alcohol use may be associated with a reduced risk of incident dementia and Alzheimer's disease (AD), while for vascular dementia, cognitive decline, and predementia syndromes the current evidence is only suggestive of a protective effect. Finally, the limited epidemiological evidence available on fruit and vegetable consumption and cognition generally supported a protective role of these macronutrients against cognitive decline, dementia, and AD. Moreover, recent prospective studies provided evidence that higher adherence to a Mediterranean-type diet could be associated with slower cognitive decline, reduced risk of progression from MCI to AD, reduced risk of AD, and decreased all-causes mortality in AD patients. These findings suggested that adherence to the MeDi may affect not only the risk for AD, but also for predementia syndromes and their progression to overt dementia. Nonetheless, at present, no definitive dietary recommendations are possible. However, high levels of consumption of fats from fish, vegetable oils, non-starchy vegetables, low glycemic fruits, and diet low in foods with added sugars and with moderate wine intake should be encouraged. In fact, this dietary advice is in accordance with recommendations for lowering the risk of cardiovascular disease, obesity, diabetes, and hypertension and might open new ways for the prevention and management of cognitive decline and dementia.

Effect of a CYP2D6 polymorphism on the efficacy of donepezil in patients with Alzheimer disease.

OBJECTIVE: To evaluate the influence of the single nucleotide polymorphism rs1080985 in the cytochrome P450 2D6 (CYP2D6) gene on the efficacy of donepezil in patients with mild to moderate Alzheimer disease (AD). METHODS: This was a multicenter, prospective cohort study of 127 white patients with AD according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association Work Group criteria. Patients were treated with donepezil 5-10 mg/daily for 6 months. Cognitive and functional statuses were evaluated at baseline and at 6-month follow-up. Response to therapy was defined according to the National Institute for Health and Clinical Excellence criteria. Compliance and drug-related adverse events were also evaluated. The analyses identifying the CYP2D6 and APOE polymorphisms were performed in blinded fashion. RESULTS: At 6-month follow-up, 69 of 115 patients (60%) were responders and 46 patients (40%) were nonresponders to donepezil treatment. A significantly higher frequency of patients with the G allele of rs1080985 was found in nonresponders than in responders (58.7% vs 34.8%, p = 0.013). Logistic regression analysis adjusted for age, sex, Mini-Mental State Examination score at baseline, and APOE demonstrated that patients with the G allele had a significantly higher risk of poor response to donepezil treatment (odds ratio 3.431, 95% confidence interval 1.490-7.901). CONCLUSIONS: The single nucleotide polymorphism rs1080985 in the CYP2D6 gene may influence the clinical efficacy of donepezil in patients with mild to moderate Alzheimer disease (AD). The analysis of CYP2D6 genotypes may be useful in identifying subgroups of patients with AD who have different clinical responses to donepezil.

Influence of cognitive impairment and comorbidity on disability in hospitalized elderly patients.

BACKGROUND: The effects of cognitive impairment and comorbidity on the prevalence of disability in elderly patients who are hospitalized in acute wards are not well defined. OBJECTIVES: To evaluate the role of comorbidity and cognitive impairment on the prevalence of disability in a cohort of hospitalized older patients. PATIENTS AND METHODS: This study included 179 patients aged 65 years and over admitted to the Geriatric Unit of the Casa Sollievo della Sofferenza Hospital, in Italy. Cognitive status was evaluated by means of the Mini Mental State Examination (MMSE) and Clinical Dementia Rating Scale (CDR); the functional status was evaluated according to the Activity of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) indices. Comorbidity was identified using the Cumulative Illness Rating Scale (CIRS index). RESULTS: Of the 179 patients enrolled 73 patients were diagnosed with dementia [Alzheimers' Disease (AD) = 49 patients, Vascular Dementia (VD) = 24 patients], 35 patients with Mild Cognitive Impairment (MCI) and 71 patients had no cognitive impairment. The severity of disability was significantly higher in patients with dementia (ADL = 3.1 +/- 2.1, IADL = 1.5 +/- 2.0) than patients with MCI (ADL = 5.1 +/- 1.4, IADL = 5.2 +/- 2.2) (p < 0.0001) and patients without cognitive impairment (ADL = 5.5 +/- 0.9, IADL = 6.4 +/- 1.9) (p < 0.0001). No significant differences in CIRS index were observed between patients with dementia and MCI and no cognitive impairment patients (Dementia = 2.4 +/- 1.4 vs MCI = 2.9 +/- 1.4 vs No cognitive impairment = 2.7 +/- 1.2; p = 0.1). Moreover, a significant correlation between cognitive impairment and functional status (MMSE/ADL: r = 0.45, p = 0.0001, MMSE/IADL: r = 0.54, p = 0.0001) but not between comorbidity and functional status (CIRS/ADL: r = 0.0007, CIRS/IADL: r = 0.040) was observed. Separating patients with dementia by diagnosis of AD or VD, no significant differences in MMSE (AD = 12.2 +/- 6.7 vs VD = 13.2 +/- 6.5, p = 0.6), CDR (AD = 2.2 +/- 0.8 vs VD = 2.1 +/- 0.7, p = 0.6), ADL (AD = 3.1 +/- 2.1 vs VD = 3.0 +/- 2.1, p = 0.8), IADL (AD = 1.3 +/- 1.9 vs VD = 2.0 +/- 2.2, p = 0.1) or CIRS (AD = 2.2 +/- 1.5 vs VD = 2.8 +/- 1.3, p = 0.06) scores were observed. CONCLUSIONS: Cognitive impairment and not comorbidity, was significantly associated with disability in hospitalized older patients.

Proton-pump inhibitors reduce the risk of uncomplicated peptic ulcer in elderly either acute or chronic users of aspirin/non-steroidal anti-inflammatory drugs.

BACKGROUND: Although administration of gastroprotective drugs may reduce the risk of peptic ulcers associated with the chronic use of non-steroidal anti-inflammatory drugs or aspirin, no consensus exists as to whether this co-therapy is effective for short-term prevention, particularly in old age. AIM: To evaluate the risk of peptic ulcer associated with acute and chronic non-steroidal anti-inflammatory drugs or aspirin therapy in elderly subjects, and the influence of antisecretory treatment on this risk. METHODS: The study included 676 elderly non-steroidal anti-inflammatory drugs or aspirin users and 2435 non-users who consecutively underwent upper gastrointestinal endoscopy. The use of non-steroidal anti-inflammatory drugs and/or aspirin as well as antisecretory drugs (H2-blockers and proton-pump inhibitors) was evaluated by a structured interview. Diagnosis of gastric and duodenal ulcer as well as Helicobacter pylori infection were carried out by endoscopy and histological examination of the gastric mucosa. RESULTS: About 47.3% of patients were acute and 52.7% chronic users of non-steroidal anti-inflammatory drugs or aspirin. The risk of peptic ulcer, adjusted for age, gender, H. pylori infection and antisecretory drug use was higher in acute (gastric ulcer: odds ratio, OR = 4.47, 95% CI: 3.19-6.26 and duodenal ulcer: OR = 2.39, 95% CI: 1.73-3.31) than chronic users (gastric ulcer: OR = 2.80, 95% CI: 1.97-3.99 and duodenal ulcer: OR = 1.68, 95% CI: 1.22-2.33). Proton-pump inhibitor treatment was associated with a reduced risk of peptic ulcer in both acute (OR = 0.70, 95% CI: 0.24-2.04) and chronic (OR = 0.32, 95% CI: 0.15-0.67) non-steroidal anti-inflammatory drugs/aspirin users. Conversely, concomitant treatment with H2-blockers was associated with a significantly higher risk of peptic ulcer both in acute (OR = 10.9, 95% CI: 3.87-30.9) and chronic (OR = 6.26, 95% CI: 2.56-15.3) non-steroidal anti-inflammatory drugs/aspirin users than non-users. Proton-pump inhibitor treatment resulted in an absolute risk reduction of peptic ulcer by 36.6% in acute and 34.6% in chronic non-steroidal anti-inflammatory drugs/aspirin users; indeed, the number needed to treat to avoid one peptic ulcer in elderly non-steroidal anti-inflammatory drugs/aspirin users was three both in acute and chronic users. CONCLUSIONS: These findings suggest that proton-pump inhibitor co-treatment is advisable in symptomatic elderly patients who need to be treated with non-steroidal anti-inflammatory drugs and/or aspirin for a short period of time.