Motor signs predict poor outcomes in Alzheimer disease.

OBJECTIVE: To examine whether the presence of motor signs has predictive value for important outcomes in Alzheimer disease (AD). METHODS: A total of 533 patients with AD at early stages (mean Folstein Mini-Mental State Examination [MMSE] 21/30 at entry) were recruited and followed semiannually for up to 13.1 years (mean 3) in five University-based AD centers in the United States and European Union. Four outcomes, assessed every 6 months, were used in Cox models: cognitive endpoint (Columbia Mini-Mental State Examination < or = 20/57 [ approximately MMSE < or = 10/30]), functional endpoint (Blessed Dementia Rating Scale > or = 10), institutionalization equivalent index, and death. Using a standardized portion of the Unified PD Rating Scale (administered every 6 months for a total of 3,149 visit-assessments, average 5.9 per patient), the presence of motor signs, as well as of individual motor sign domains, was examined as time-dependent predictor. The models controlled for cohort, recruitment center, sex, age, education, a comorbidity index, and baseline cognitive and functional performance. RESULTS: A total of 39% of the patients reached the cognitive, 41% the functional, 54% the institutionalization, and 47% the mortality endpoint. Motor signs were noted for 14% of patients at baseline and for 45% at any evaluation. Their presence was associated with increased risk for cognitive decline (RR, 1.72; 95% CI, 1.24 to 2.38), functional decline (1.80 [1.33 to 2.45]), institutionalization (1.68 [1.26 to 2.25]), and death (1.38 [1.05 to 1.82]). Tremor was associated with increased risk for reaching the cognitive and bradykinesia for reaching the functional endpoints. Postural-gait abnormalities carried increased risk for institutionalization and mortality. Faster rates of motor sign accumulation were associated with increased risk for all outcomes. CONCLUSIONS: Motor signs predict cognitive and functional decline, institutionalization, and mortality in Alzheimer disease. Different motor sign domains predict different outcomes.

Motor signs during the course of Alzheimer disease.

BACKGROUND: Motor signs (MOSIs) are common in Alzheimer disease (AD) and may be associated with rates of cognitive decline, mortality, and cost of care. OBJECTIVE: To describe the progression and identify predictors of individual MOSIs in AD. METHODS: A cohort of 474 patients with AD at early stages was followed semiannually for up to 13.1 years (mean 3.6 years) in five centers in Europe and the United States. MOSIs were rated using a standardized portion of the Unified Parkinson's Disease Rating Scale. Overall, 3,030 visits/assessments of MOSIs (average 6.4/patient) were performed. Prevalence and incidence rates were calculated, and cumulative risk graphs were plotted for individual non-drug-induced MOSI domains. Rates of change over time taking into account potential covariates were also estimated. With use of each MOSI domain as outcome in Cox models, predictors of MOSI incidence were identified. RESULTS: At least one MOSI was detected in 13% of patients at first examination and in 36% for the last evaluation. Total MOSI score increased at an annual rate of 3% of total possible score. Rates of annual change for speech/facial expression (4%), rigidity (2.45%), posture/gait (3.9%), and bradykinesia (3.75%) were of similar magnitude, and their occurrence increased from first (3 to 6%) to last (22 to 29%) evaluation. Tremor was less frequent throughout the course of the disease (4% at first and 7% at last evaluation) and worsened less (0.75% increase/year). CONCLUSIONS: Most motor signs occur frequently and progress rapidly in Alzheimer disease. Tremor is an exception in that it occurs less frequently and advances at slower rates.

Source memory and encoding strategy in normal aging.

Of the memory deficits associated with aging, elders are most impaired at attributing the source to remembered information. Additionally, aging is marked by a decrease in the use of encoding strategies that are thought to enhance the acquisition and retention of information. We examined how manipulating the encoding strategy during acquisition affected item and source memory in 32 young and 68 elderly participants. Elderly participants were dichotomized into young-old and old-old based upon the median age (74 years). Memory was assessed using Word List A from the California Verbal Learning Test (CVLT) and its alternate form. Encoding strategy was manipulated by semantic clustering. For the Blocked List, words were presented grouped into their semantic categories, whereas for the Unblocked List categories were intermixed within the list. Item and source memory judgments were made 20 minutes after the final CVLT recall trial and again one week later. Results revealed a disproportionate decline in source, compared to item memory in the two older groups. Semantic blocking enhanced item memory for the elders, but not for the young. The amount of semantic clustering performed by the elders showed a decline with age and was positively related to source performance. Results also suggest that subtle age-related changes in semantic knowledge may be related to declines in semantic clustering and memory performance.

Effects of inter-item lag on recognition memory in seizure patients preceding temporal lobe resection: evidence from event-related potentials.

The electrophysiological correlates of word recognition are well characterized. Repeated 'old' words evoke a more positive-going waveform starting at approximately 300 ms compared with first-presented, 'new' words. The old/new effect is thought to be generated, in part, by structures within the medial temporal lobe. In the present study, event-related potentials were recorded during a continuous verbal recognition memory task in unoperated patients with either left (L) or right (R) unilateral temporal lobe epilepsy (Epil) and neurologically intact controls. To manipulate the difficulty of the memory task, the lag between the initial and subsequent presentation of the repeated words was varied from one, four to 16 items. In the controls, ERPs to old words were more positive going than new words from approximately 350-650 ms. The old/new effect diminished as the inter-item lag increased. Patient old/new effects showed a later onset (450 ms) and resolution (750 ms) compared with the controls. Furthermore, the late component of the old/new effect was significantly reduced in the L Epil. Although patient behavioral performance did not differ significantly from that of the controls, neuropsychological testing revealed impaired verbal memory function in the L Epil patients. It is concluded that the reduced old/new effect in the L Epil patients provides evidence that medial temporal lobe structures contribute to the scalp-recorded old/new effect.

Event-related potentials in homosexual and heterosexual men and women: sex-dimorphic patterns in verbal asymmetries and mental rotation.

To elucidate neurobiological factors related to gender and sexual orientation, event-related brain potentials of 20 heterosexual (HT) men, 20 HT women, 20 homosexual (HM) men, and 20 HM women were examined for neurophysiological differences. Cognitive tasks which typically elicit sex differences were administered. A mental rotation (MR) task assessed spatial ability, and a divided-visual-field lexical-decision/semantic monitoring task (LD/SM) assessed verbal ability and relative degrees of language lateralization. Slow wave activity recorded during MR was greater for HT men than for HT women and gay men. N400 asymmetries recorded during the LD/SM task revealed differences between men and women, but no intrasex differences.

A neuropsychologic profile of homosexual and heterosexual men and women.

To examine the applicability of psychosexual differentiation theory to the development of sexual orientation, heterosexual (HT) women, HT men, lesbians, and gay men (20 per group) completed a lexical-decision/semantic monitoring task (LD/SM) to assess verbal ability, as well as a Water Level Task (WLT) and two Mental Rotation (MR) Tasks designed to assess spatial ability. All tests have been shown to differentiate HT men and women. Results replicated previously reported sex differences between the HT men and women. Further, gay men performed akin to HT women on the verbal task and the MR tasks, but not in the WLT. Lesbians, however, primarily performed in a sex-typical manner. The dissociation in sex-atypicality between lesbians and gay men is discussed in relation to neurobiological factors related to the development of both sex-dimorphic cognitive ability and sexual orientation.

Relation between language lateralisation and spatial ability in gay and straight women and men.

Delineating the relationship between language lateralisation and spatial ability remains an elusive goal. To explore the association of sexual orientation to the language lateralisation/spatial ability relationship, heterosexual (HT) women, HT men, lesbians, and gay men (20 per group) completed a divided-visual-field lexical-decision task to assess relative degrees of language lateralisation, as well as a Water Level Task (WLT) and two Mental Rotation (MR) Tasks designed to assess spatial ability. A significant cross-sex shift was revealed in the language lateralisation of gay men. Further, language lateralisation positively correlated with MR ability in HT men and tended to positively correlate with spatial perception in HT women. No significant associations were revealed in homosexual subjects. Different patterns of functional hemispheric asymmetry in homosexual and heterosexual individuals are discussed in relation to early neurobiological factors influencing the development of sexual orientation.