PET network abnormalities and cognitive decline in patients with mild cognitive impairment.

Temporoparietal and posterior cingulate metabolism deficits characterize patients with Alzheimer's disease (AD). A H(2)(15)O resting PET scan covariance pattern, derived by using multivariate techniques, was previously shown to discriminate 17 mild AD patients from 16 healthy controls. This AD covariance pattern revealed hypoperfusion in bilateral inferior parietal lobule and cingulate; and left middle frontal, inferior frontal, precentral, and supramarginal gyri. The AD pattern also revealed hyperperfusion in bilateral insula, lingual gyri, and cuneus; left fusiform and superior occipital gyri; and right parahippocampal gyrus and pulvinar. In an independent sample of 23 outpatients with mild cognitive impairment (MCI) followed at 6-month intervals, the AD pattern score was evaluated as a predictor of cognitive decline. In this MCI sample, an H2(15)O resting PET scan was carried out at baseline. Mean duration of follow-up was 48.8 (SD 15.5) months, during which time six of 23 MCI patients converted to AD. In generalized estimating equations (GEE) analyses, controlling for age, sex, education, and baseline neuropsychological scores, increased AD pattern score was associated with greater decline in each neuropsychological test score over time (Mini Mental State Exam, Selective Reminding Test delayed recall, Animal Naming, WAIS-R digit symbol; Ps<0.01-0.001). In summary, a resting PET covariance pattern previously reported to discriminate AD patients from control subjects was applied prospectively to an independent sample of MCI patients and found to predict cognitive decline. Independent replication in larger samples is needed before clinical application can be considered.     

Seizure Elicitation Blocked by Pretreatment with Lidocaine

A patient is reported in whom pretreatment with intravenous lidocaine resulted in failure to elicit a seizure even at stimulus intensity markedly greater than that used successfully at prior and subsequent treatments. Together with one other report, this experience suggests that lidocaine may prevent a seizure by raising the seizure threshold. An alternative explanation is proposed for the classic findings of Ottosson that lidocaine-modified seizures are reduced in therapeutic efficacy.     

Relative response of endogenous and non-endogenous symptoms to electroconvulsive therapy

A sample of patients with endogenous depression (RDC), who had only a partial response to electroconvulsive therapy (ECT), was identified from a larger group of patients participating in a study of the affective and cognitive effects of low-dose titrated ECT. Using symptom scores on the Hamilton Rating Scale for Depression, subscales were constructed to reflect Klein's formulation of endogenomorphic depression, the RDC for endogenous subtype, and the DSM-III criteria for melancholia. Regardless of the subscale used, no evidence was obtained that endogenous symptoms were more responsive to ECT than non-endogenous symptoms.     

A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities

BACKGROUND: Controversy persists about the use of right unilateral (RUL) and bilateral (BL) electroconvulsive therapy (ECT). While RUL ECT results in less severe short-term and long-term cognitive effects, there is concern that it is less efficacious than BL ECT. METHODS: In a double-blind study, 80 depressed patients were randomized to RULECT, with electrical dosages 50%, 150%, or 500% above the seizure threshold, or BL ECT, with an electrical dosage 150% above the threshold. Depression severity and cognitive functioning were assessed before, during, immediately after, and 2 months after ECT. Compared with baseline, responders had at least a 60% reduction in symptom scores 1 week after ECT, and were monitored for relapse for 1 year. RESULTS: High-dosage RUL and BL ECT were equivalent in response rate (65%) and approximately twice as effective as low-dosage (35%) or moderate-dosage (30%) unilateral ECT. During the week after the randomized phase, BL ECT resulted in greater impairment than any dosage of unilateral ECT in several measures of anterograde and retrograde memory. Two months after ECT, retrograde amnestic deficits were greatest among patients treated with BL ECT. Thirty-three (53%) of the 62 patients who responded to ECT relapsed, without treatment group differences. The relapse rate was greater in patients who had not responded to adequate pharmacotherapy prior to ECT and who had more severe depressive symptoms after ECT. CONCLUSION: Right unilateral ECT at high dosage is as effective as a robust form of BL ECT, but produces less severe and persistent cognitive effects.     

The effects of electroconvulsive therapy on memory of autobiographical and public events

BACKGROUND: Retrograde amnesia is the most persistent cognitive adverse effect of electroconvulsive therapy (ECT); however, it is not known whether ECT has differential effects on autobiographical vs impersonal memories. This study examined the short- and long-term effects of differing forms of ECT on memory of personal and impersonal (public) events. METHODS: Fifty-five patients with major depression were randomly assigned to right unilateral (RUL) or bilateral (BL) ECT, each at either low or high electrical dosage. The Personal and Impersonal Memory Test was administered by blinded raters at baseline, during the week after ECT, and at the 2-month follow-up. Normal controls were tested at matched intervals. RESULTS: Shortly after ECT, patients recalled fewer events and event details than controls, with the deficits most marked for impersonal compared with personal events. Bilateral ECT caused more marked amnesia for events and details than RUL ECT, and especially for impersonal memories. These effects were independent of electrical dosage and clinical outcome. At the 2-month follow-up, patients had reduced retrograde amnesia, but continued to show deficits in recalling the occurrence of impersonal events and the details of recent impersonal events. CONCLUSIONS: The amnestic effects of ECT are greatest and most persistent for knowledge about the world (impersonal memory,) compared with knowledge about the self (personal memory), for recent compared with distinctly remote events, and for less salient events. Bilateral ECT produces more profound amnestic effects than RUL ECT, particularly for memory of impersonal events.     

The efficacy of ECT in mixed affective states

ECT is efficacious in the treatment of both the depressed and manic phases of bipolar disorder. While ECT is believed to be equally efficacious in the treatment of mixed affective states, to our knowledge there are no empirical studies on this issue. A chart review study was conducted to compare treatment response and clinical course in three groups of patients who received ECT in a general hospital service: bipolar depressed (n = 38), bipolar manic (n = 5), and bipolar mixed (n = 10), diagnosed by DSM-IV criteria. All three groups showed robust response rates, but the number of days of hospitalization was significantly longer in the mixed group (mean 30, SD 19.0 days) compared with the depressed group (mean 19.0, SD 10.9 days, t = 2.4, p < 0.03). There was a trend for the number of ECT treatments to be greater in the mixed compared with the depressed group. These findings indicate that patients with mixed affective states do respond well to a course of ECT, but the longer hospital stays and greater number of ECT treatments suggest that they may be more difficult to treat with ECT than patients with pure bipolar depression or bipolar mania.