Jared R. Tinklenberg

Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins

A molecular test for Alzheimers disease could lead to better treatment and therapies. We found 18 signaling proteins in blood plasma that can be used to classify blinded samples from Alzheimers and control subjects with close to 90% accuracy and to identify patients who had mild cognitive impairment that progressed to Alzheimers disease 2–6 years later. Biological analysis of the 18 proteins points to systemic dysregulation of hematopoiesis, immune responses, apoptosis and neuronal support in presymptomatic Alzheimers disease.

Estrogen Replacement Therapy and Memory in Older Women

OBJECTIVE: To study the relationship between estrogen hormone replacement therapy and recall of proper names and words in cognitively intact older women.

Effects of phosphatidylserine in age-associated memory impairment.

We treated 149 patients meeting criteria for age‐associated memory impairment (AAMI) for 12 weeks with a formulation of phosphatidylserine (100 mg BC‐PS tid) or placebo. Patients treated with the drug improved relative to those treated with placebo on performance tests related to learning and memory tasks of daily life. Analysis of clinical subgroups suggested that persons within the sample who performed at a relatively low level prior to treatment were most likely to respond to BC‐PS. Within this subgroup, there was improvement on both computerized and standard neuropsychological performance tests, and also on clinical global ratings of improvement. The results suggest that the compound may be a promising candidate for treating memory loss in later life. NEUROLOGY 1991;41:644‐649

Effects of perceptual and cognitive difficulty on P3 and RT in young and old adults

Ten healthy old and 10 healthy young subjects each received a series of trials in a memory retrieval task similar to that devised by Sternberg (1967). On each trial the subject saw a memory set of 2 or 4 digits (set size) followed by a probe. The task was to indicate whether the probe was a positive or negative instance (response type) of the memory set for that trial. On half the trials, the probe digits were degraded by a mask of random dots (stimulus quality). For both young and old subjects, RT was later to probes following the larger set size, later to degraded probes, and later to negative probes. For the young subjects only, P3 latency was delayed by the same variables affecting RT although to a lesser degree. P3 latency in the elderly responded quite differently: it was unaffected by set size or response type. However, P3 was somewhat delayed by the degraded probes suggesting that the failure to reflect set size or ceiling effect in the elderly. The correlation between single-trial P3 latency and RT in the elderly is lower than in the young. The data are discussed in terms of age-related differences in the meaning of P3 latency.

Donepezil and flight simulator performance: Effects on retention of complex skills

Abstract—We report a randomized, double-blind, parallel group, placebo-controlled study to test the effects of the acetylcholinesterase inhibitor, donepezil (5 mg/d for 30 days), on aircraft pilot performance in 18 licensed pilots with mean age of 52 years. After 30 days of treatment, the donepezil group showed greater ability to retain the capacity to perform a set of complex simulator tasks than the placebo group, p < 0.05. Donepezil appears to have beneficial effects on retention of training on complex aviation tasks in nondemented older adults.

Marihuana and Temporal Disintegration

High oral doses of marihuana extract, calibrated for content of 1 (—)-Δ1-tetrahydrocannabinol, significantly impaired the serial coordination of cognitive operations during a task that required sequential adjustments in reaching a goal. This disintegration of sequential thought is related to impaired immediate memory.

Convergent behavioral and neuropsychological evidence for a distinction between identification and production forms of repetition priming

Four experiments examined a distinction between kinds of repetition priming which involve either the identification of the form or meaning of a stimulus or the production of a response on the basis of a cue. Patients with Alzheimers disease had intact priming on picture-naming and category-exemplar identification tasks and impaired priming on word-stem completion and category-exemplar production tasks. Division of study-phase attention in healthy participants reduced priming on word-stem completion and category-exemplar production tasks but not on picture-naming and category-exemplar identification tasks. The parallel dissociations in normal and abnormal memory cannot be explained by implicit-explicit or perceptual-conceptual distinctions but are explained by an identification-production distinction. There may be separable cognitive and neural bases for implicit modulation of identification and production forms of knowledge.

Combined assessment of tau and neuronal thread protein in Alzheimer’s disease CSF

Objective: Comparative study of CSF levels of tau and AD7C-neuronal thread protein (NTP) in patients with AD and control subjects. Background: AD is characterized by neurofibrillary tangles composed of the abnormally hyperphosphorylated microtubule-associated protein tau. AD7C-NTP is a proposed AD marker expressed at early stages of neurofibrillary degeneration. Methods: Enzyme-linked immunosorbent assays specific for tau and AD7C-NTP. CSF samples were obtained from 35 demented patients (25 with antemortem clinical diagnosis of probable AD, 5 with neuropathologic diagnosis of definite AD, 5 with Lewy body pathology), 29 nondemented patients with PD, and 16 elderly healthy control subjects. Receiver operating characteristics (ROC) and multivariate discriminant analysis for AD versus controls. Correlational analysis of CSF tau and AD7C-NTP and of each marker with Mini-Mental State Examination (MMSE) scores was performed. Results: Levels of both tau and AD7C-NTP were significantly elevated in the AD patients compared with control subjects. ROC analysis showed that CSF tau distinguished between patients with AD and nondemented control subjects with 63% sensitivity and 89% specificity, AD7C-NTP with 70% sensitivity and 87% specificity. Combined evaluation of both markers with discriminant analysis raised the specificity to 93% at a 63% sensitivity level. Both markers positively correlated with each other within the AD group, but not among control subjects. CSF levels of AD7C-NTP, but not of tau, showed a small but significant inverse correlation ( r = −0.43) with MMSE scores of AD patients. Conclusions: CSF levels of tau and AD7C-NTP may be useful biomarkers for AD.

Correlates of memory decline : a 4-year longitudinal study of older adults with memory complaints

Change in memory performance and its correspondence to change in speed of performance and self-reported memory functioning were investigated longitudinally in 30 older adults with memory complaints. Subjects were assessed by self-report questionnaires and cognitive tests 3 times, at near 2-year intervals. A significant decline in word-recall scores was found, which was accompanied at the group level by significant self-reported decline in everyday memory functioning and nonsignificant decline in Wechsler Adult Intelligence Scale Digit Symbol scores (alpha = .05). The oldest subjects showed the most substantial declines in memory performance. At the individual level, however, memory change did not significantly correlate with either change in self-reports or change in Digit Symbol scores. Although these results do not support a cognitive slowing model of decline at the intraindividual level, they do have implications for intervention of age-related memory decline.

Validation of a 26-point Telephone version of the Mini-Mental State Examination

The objective of this study was to assess the convergent validity of a 26-point Telephone Mini-Mental State Examination (MMSE) in a longitudinal cohort of 46 Alzheimer’s disease (AD) patients. Paired in-person and telephone MMSE observations were collected within 35 days of each other. The setting was the Stanford/VA Alzheimer’s Center in Palo Alto, California, and patients’ residences. The 30-point Folstein MMSE was administered in-person, and a 26-point telephone version of the MMSE, adapted from the Adult Lifestyles and Function Interview (ALFI)-MMSE. Total scores for the in-person and telephone MMSE versions correlated strongly (Pearson’s r = .88, P < .001). Hearing impairment and education level did not significantly affect telephone-based performance. The Telephone MMSE can be used to validly estimate in-person MMSE scores of patients with AD. Use of this practical measure can enhance reassessment if returning to the clinic is difficult or if a change in the patient’s medical condition merits a check of mental status by telephone.