Reduced Hippocampal Glutamate and Posterior Cingulate N-Acetyl Aspartate in Mild Cognitive Impairment and Alzheimer's Disease Is Associated with Episodic Memory Performance and White Matter Integrity in the Cingulum: A Pilot Study.

Identification of biological changes underlying the early symptoms of Alzheimer's disease (AD) will help to identify and stage individuals prior to symptom onset. The limbic system, which supports episodic memory and is impaired early in AD, is a primary target. In this study, brain metabolism and microstructure evaluated by high field (7 Tesla) proton magnetic resonance spectroscopy (1H-MRS) and diffusion tensor imaging (DTI) were evaluated in the limbic system of eight individuals with mild cognitive impairment (MCI), nine with AD, and sixteen normal elderly controls (NEC). Left hippocampal glutamate and posterior cingulate N-acetyl aspartate concentrations were reduced in MCI and AD compared to NEC. Differences in DTI metrics indicated volume and white matter loss along the cingulum in AD compared to NEC. Metabolic and microstructural changes were associated with episodic memory performance assessed using Craft Story 21 Recall and Benson Complex Figure Copy. The current study suggests that metabolite concentrations measured using 1H-MRS may provide insight into the underlying metabolic and microstructural processes of episodic memory impairment.

Treatment of asymptomatic UTI in older delirious medical in-patients: A prospective cohort study.

BACKGROUND: Despite clinical practice guidelines, asymptomatic bacteriuria (ASB) in older people is frequently treated. A common reason for treating ASB is a change in mental status. OBJECTIVE: To determine how often asymptomatic UTI is treated in older medically ill delirious individuals and its association with functional recovery. METHODS: Consecutive older medical in-patients were screened for delirium, and followed in hospital. Treatment for asymptomatic UTI was defined as documented treatment for a possible urinary tract infection with antibiotics, without concurrent infectious or urinary symptoms. The primary outcome was functional recovery at discharge or 3 months post-discharge. Poor functional recovery was defined by any one of death, new permanent long-term institutionalization or decreased ability to perform activities of daily living. RESULTS: The study sample comprised 343 delirious in-patients, of which 237 (69%) had poor functional recovery. Ninety two (27%) delirious in-patients were treated for asymptomatic UTI. Treatment for asymptomatic UTI was associated with poor functional recovery compared to other delirious in-patients (RR 1.30, 95% CI: 1.14-1.48 overall). Similar results were seen when the analysis was restricted to only bacteriuric delirious individuals. Seven (7.5%) individuals treated for asymptomatic UTI developed Clostridium difficile infection compared to eight (3.2%) in the remainder of the delirious cohort (OR 2.45, 95% CI: 0.86-6.96). CONCLUSIONS: These results suggest that treatment of asymptomatic UTI in older medical in-patients with delirium is common, and of questionable benefit. Further research is needed to establish guidelines to minimize over-treatment of UTI in older delirious in-patients.

Poor functional recovery after delirium is associated with other geriatric syndromes and additional illnesses.

BACKGROUND: Delirious individuals are at increased risk for functional decline, institutionalization and death. Delirium is also associated with other geriatric syndromes, behavioral care issues, and new illnesses. The objectives of this study were to determine how often certain geriatric syndromes, care issues, and additional diagnoses occur in delirious individuals, and to see whether they correlate with worse functional recovery. METHODS: Consecutive delirious older medical in-patients (n = 343) were followed for the occurrence of geriatric syndromes (falls, pressure ulcers, poor oral intake, and aspiration), care issues (refusing treatments or care, need for sitters, security services, physical restraints, and new neuroleptic medications) and additional diagnoses occurring after the third day of admission. Poor functional recovery was defined by any one of death, permanent institutionalization or increased dependence for activities of daily living (ADLs) at discharge or three months after discharge from hospital, elicited through chart review or a follow-up telephone interview. RESULTS: Poor functional recovery was seen in 237 (69%) delirious patients. Geriatric syndromes and additional illnesses were common and associated with poor functional recovery (falls in 21%, adjusted OR 2.27; possible aspiration in 26%, adjusted OR 3.06; poor oral intake in 49%, adjusted OR = 2.31; additional illnesses in 38%, adjusted OR 3.54). Care issues were also common (range 9%-54%) but not associated with poor recovery. CONCLUSIONS: Geriatric syndromes, behavioral care issues and additional illnesses are common in delirium. Future studies should assess whether monitoring for and intervening against geriatric syndromes and additional illnesses may improve functional outcomes after delirium.

Prognosis of delirium in hospitalized elderly: worse than we thought.

BACKGROUND: Despite treatment of the associated condition, delirious persons do not always recover for unknown reasons. We sought to determine early prognostic indicators of poor recovery following an episode of delirium in older medical in-patients. METHODS: Between October 2009 and July 2011, consecutively admitted older (≥70 years old) medical in-patients at the London Health Sciences Centre (Ontario) were screened for delirium. Delirious patients were followed. The primary outcome was poor recovery, in delirious patients, defined by death, long-term institutionalization, or functional decline (decreased activities of daily living), at discharge or 3 months after discharge, elicited from the medical chart or post-discharge caregiver telephone interviews. RESULTS: One thousand two hundred thirty-five in-patients (mean age 82.6 years, 42% men) were screened, delirium occurred in 355 (29%). Follow-up data was known on 342 (96%), and 237 (69%) had poor recovery: 55 died (54 in hospital and one after discharge), 136 were permanently institutionalized (86 directly from hospital and 50 after discharge), and 46 had functional decline (at a median of 103 days after discharge). Poor recovery was associated in the derivation sample with advanced age, lower baseline function, hypoxia, higher delirium severity scores, and acute renal failure; this was predictive of poor recovery in the validation sample (receiver operating characteristic area 0.68, 95% confidence interval: 0.57-0.79); however, even individuals with "low" risk had high (50%) poor recovery rates. INTERPRETATION: Poor recovery after delirium is common and associated with certain characteristics. However, even "lower risk" delirious individuals do poorly. More research is needed to understand prognostic factors in delirium.

A randomized, double-blind, placebo controlled crossover trial of nimodipine in older persons with detrusor instability and urge incontinence.

PURPOSE: We evaluated the efficacy of nimodipine, a dihydropyridine calcium channel blocker that relaxes vascular and nonvascular smooth muscle, for geriatric urge incontinence. MATERIALS AND METHODS: A randomized, double-blind, placebo controlled crossover trial of 30 mg. nimodipine twice daily for 3 weeks in older persons with detrusor instability and chronic urge incontinence was done. A total of 86 participants with a mean age of 73.4 years were randomized. The primary outcome was the number of incontinent episodes, as measured by the self completion of a 5-day voiding record. Secondary outcomes included the impact of urinary incontinence on quality of life measured with a modified incontinence impact questionnaire (mIIQ) and symptoms, as measured by the American Urological Association (AUA) symptom score. RESULTS: A total of 76 (88.4%) participants completed the study. There was no significant difference in the number of incontinent episodes with nimodipine versus placebo, which included a difference of 0.03 incontinent episodes during a 5-day period (p =0.98, 95% confidence interval -2.7 to 2.8). Scores on the mIIQ and the AUA symptom score were not significantly different with nimodipine versus placebo (p = 0.07 and 0.22, respectively). Regardless of initial treatment, participants had improvement with time, that is a period effect, of incontinent episodes (p <0.0001), mIIQ scores (p = 0.0002) and AUA symptom score values (p <0.0001). CONCLUSIONS: Treatment of geriatric urge incontinence with 30 mg. nimodipine twice daily did not result in a significant improvement of incontinent episodes, mIIQ scores or AUA symptom scores.