Education as Proxy for Cognitive Reserve in a Large Elderly Memory Clinic: 'Window of Benefit'.

BACKGROUND: The role of cognitive reserve (CR) to explain individual differences in cognitive functioning is unclear in memory clinic patients. OBJECTIVE: To examine the cross-sectional effect of CR on cognition in relation to levels of neurodegeneration in a large elderly single-center memory clinic population. METHODS: We included patients with subjective cognitive impairment (SCI, n = 481), mild cognitive impairment (MCI, n = 628) or Alzheimer's disease (AD, n = 1,099). Education was used as proxy for CR and visually rated medial temporal lobe atrophy (MTA) on CT was used as parameter of neurodegeneration. Relations between CR, cognition, and MTA were analyzed with multiple linear regression adjusted for age, sex, and cerebral atrophy. In addition, we examined if education affects the relation between MTA and cognition using an interaction variable. RESULTS: Education was significantly related to all measures of cognition including subtests with an explained variance of education as a determinant of cognition of 11%. More highly educated patients had more advanced levels of MTA at the same level of cognition. All these results were stronger or only present in demented compared to non-demented patients but appeared no longer significant in those with lowest overall cognition. The interaction effect was significant indicating that with more advanced MTA, less cognitive decline was shown in higher educated patients. CONCLUSION: Education is a very strong determinant of cognition in an elderly memory clinic population. The positive effect of education was stronger in demented than in non-demented patients but disappeared in those with the lowest cognitive scores indicating a "window of CR benefit".

Cerebral White Matter Lesions have Low Impact on Cognitive Function in a Large Elderly Memory Clinic Population.

BACKGROUND: Evidence suggests that cerebral white matter lesions (WML) play a role in cognitive decline. OBJECTIVE: To assess the impact of cerebral WML on cognitive function relative to absence or presence of medial temporal atrophy (MTA) in a large single-center memory clinic population. METHODS: Patients included had subjective cognitive impairment (SCI, n = 333), mild cognitive impairment (MCI, n = 492) and Alzheimer's disease (AD, n = 832). The relationships between visually rated WML (Fazekas scale, 0-3) on brain Computed Tomography and CAMCOG memory and non-memory function were investigated with regression analysis adjusted for age, gender and education in combined patient groups. We assessed possible interaction versus addition effects of these relationships with visually rated MTA (Scheltens scale). RESULTS: The highly statistical significant relationship between WML and memory function was no longer significant when MTA was taken into account. However, the strong significant relationship between WML and non-memory function remained significant after adjustment for MTA, but the explained variance attributed to WML was only 1.3%. There was no interaction between WML and MTA on CAMCOG test scores. In addition, shown by a 2×2 factorial model by presence versus absence of WML and MTA, WML affected non-memory function only in the presence of MTA. CONCLUSION: Our data suggest that presence of WML is associated with lower non-memory cognitive function but this effect is conditional on the presence of pre-existing MTA. The very small explained variance suggests little impact of WML to the clinical profile of a memory clinic patient.

Practical use of visual medial temporal lobe atrophy cut-off scores in Alzheimer's disease: Validation in a large memory clinic population.

OBJECTIVE: To provide age-specific medial temporal lobe atrophy (MTA) cut-off scores for routine clinical practice as marker for Alzheimer's disease (AD). METHODS: Patients with AD (n = 832, mean age 81.8 years) were compared with patients with subjective cognitive impairment (n = 333, mean age 71.8 years) in a large single-centre memory clinic. Mean of right and left MTA scores was determined with visual rating (Scheltens scale) using CT (0, no atrophy to 4, severe atrophy). Relationships between age and MTA scores were analysed with regression analysis. For various MTA cut-off scores, decade-specific sensitivity and specificity and area under the curve (AUC) values, computed with receiver operator characteristic curves, were determined. RESULTS: MTA strongly increased with age in both groups to a similar degree. Optimal MTA cut-off values for the age ranges <65, 65-74, 75-84 and ≥85 were: ≥1.0, ≥1.5, ≥ 2.0 and ≥2.0. Corresponding values of sensitivity and specificity were 83.3% and 86.4%; 73.7% and 84.6%; 73.7% and 76.2%; and 84.0% and 62.5%. CONCLUSION: From this large unique memory clinic cohort we suggest decade-specific MTA cut-off scores for clinical use. After age 85 years, however, the practical usefulness of the MTA cut-off is limited. KEY POINTS: • We suggest decade-specific MTA cut-off scores for AD. • MTA cut-off after the age of 85 years has limited use. • CT is feasible and accurate for visual MTA rating.

Low Prevalence of Mixed Dementia in a Cohort of 2,000 Elderly Patients in a Memory Clinic Setting.

BACKGROUND: It is generally assumed that with increasing age, pathology in clinically diagnosed Alzheimer's disease (AD) becomes more mixed, i.e., co-existence of amyloid plaques and cerebrovascular pathology. OBJECTIVE: To test the hypothesis of increasing prevalence of mixed dementia in late-onset clinically diagnosed Alzheimer's disease (AD) in a single-center memory clinic population. METHODS: Patients included had diagnoses of AD (n = 832), subjective cognitive impairment (SCI, n = 333), mild cognitive impairment (MCI, n = 492), vascular dementia (VaD, n = 57), other dementia (n = 53), or other diagnosis (n = 233). Prevalence of severe white matter lesions (WML) was defined as a score of 2 or higher on the Fazekas-scale on brain computed tomography to classify AD patients as having mixed dementia. We examined the effect of age on WML using multiple linear regression analysis, and AD patients were compared to SCI to determine the effect of disease on WML. RESULTS: Prevalence of severe WML was 33.6% in AD patients (mixed dementia), 11.4% in SCI, 22.7% in MCI, 75.4% in VaD, 3.8% in other dementia, and 15.5% in other diagnosis. With increasing age there was a significant and similar increase of WML scores in SCI, MCI, AD, other dementia, and other diagnosis, indicating no effect modification by AD. The difference between AD patients and SCI averaged 0.16 on the WML score and difference in percentage severe WML between AD and SCI patients was 15% across all ages. CONCLUSION: We found a low prevalence of mixed dementia. Furthermore, severe WML in AD was largely explained by age rather than effect of disease.

Short- and long-term neurocognitive functioning after electroconvulsive therapy in depressed elderly: a prospective naturalistic study.

BACKGROUND: It is generally assumed that the elderly patients are more vulnerable to cognitive side effects after electroconvulsive therapy (ECT) than younger depressed patients. The current study aims to evaluate the nature and extent of changes across multiple domains of neurocognitive functioning in a group of elderly depressed patients after ECT. METHODS: In this prospective naturalistic study, we included 42 depressed patients aged ≥55 years. Global cognitive function, memory, and executive function were assessed before ECT treatment and within one week (short-term post-ECT) and six months after ECT (long-term post-ECT). Associations between cognitive functioning and electrode placement, total number of treatment sessions, age, and the severity of depression at the time of cognitive measurement were studied. RESULTS: Our data offered no evidence of decline for any of the neurocognitive tests after ECT, given its power to detect the difference. Post-ECT improvement of neurocognitive functioning was statistically significant for the Mini-Mental State Examination, Visual Association Test, 10 Words Verbal Learning Test, and Expanded Mental Control Test. Effect sizes were medium to large. After six months, compared with post-ECT performance, statistically significant improvement was found only for the Trail Making Test-A and the Letter Fluency Test with small to medium effect sizes. CONCLUSIONS: In our severely depressed elderly patients, neurocognitive performance improved or did not change after ECT. Patients with poor cognitive function were not able to participate in neuropsychological assessment before ECT started. Consequently these results may not apply to patients with more severe cognitive impairment prior to the start of ECT.

The effects of ECT on cognitive functioning in the elderly: a review.

BACKGROUND: Electroconvulsive therapy (ECT) as a single course or in maintenance form (M-ECT) is an effective treatment in depressed elderly. However, ECT may have adverse effects on cognition. OBJECTIVE: To review all studies from 1980-2006 on ECT and cognition in the elderly with a minimum age of 55 years or a mean age of 55 years, and with valid measurements of cognition before and after ECT. RESULTS: Nine out of the 15 eligible studies were focused exclusively on the elderly. Three studies reported verbal learning- and recall problems post ECT, while three studies found positive effects of ECT on memory, speed of processing and concentration. Global cognitive functioning in patients with cognitive impairment improved in all studies. At follow up, most studies reported improvement of cognitive functions. Learning verbal information and executive functioning were impaired in M-ECT patients whereas global cognition remained stable after M-ECT over a year. CONCLUSIONS: To date research of ECT on cognitive functioning in the elderly is very limited. Small sample size, lack of controls, use of a single screening instrument and a short follow up period may explain the conflicting results. Given the clinical importance, more extensive research on cognition in elderly treated with ECT is urgently needed.