The clock drawing test is an important contribution to the Mini Mental State Examination in screening for cognitive impairment.

BACKGROUND: The clock drawing test (CDT) and the Mini Mental State Examination (MMSE) are frequently used screening instruments for cognitive impairment, however, the precise contribution of the CDT to the MMSE is largely unknown. METHODS: We studied patients with subjective cognitive impairment (SCI, n = 481), mild cognitive impairment (MCI, n = 628) and Alzheimer's disease (AD, n = 1099). Discrimination between patients was examined with multiple logistic regression, adjusted for age, sex, and education. Four groups were constructed based on a normal/abnormal MMSE (cut-off <24/30) versus normal/abnormal CDT (cut-off ≤2/3). Visually rated medial temporal lobe atrophy (MTA) on CT was used as parameter of neurodegeneration. RESULTS: The CDT significantly contributed to the MMSE in discriminating SCI from both MCI and AD patients. Our four group analyses showed that of those patients with a normal MMSE and incorrectly classified as SCI, an abnormal CDT could significantly identify 10.0% as MCI and 13.2% as AD. Among those with an abnormal MMSE, the percentage AD patients shifted from 53.1% to 82.1% due to an abnormal CDT. Presence of an abnormal CDT was significantly related to MTA increase, regardless of the MMSE score. CONCLUSION: The CDT is an important additional screening tool to the MMSE. An abnormal CDT with a normal MMSE is an indicator for cognitive impairment. An abnormal CDT in combination with an abnormal MMSE can be considered as an indicator of disease progression.

Basal ganglia calcifications: No association with cognitive function.

BACKGROUND AND PURPOSE: Basal ganglia calcifications (BGC), a form of vascular calcification, are a common brain computed tomography (CT) finding. We investigated whether BGC are associated with cognitive function and examined the association between vascular risk factors and BGC. MATERIAL AND METHODS: Patients who visited a memory clinic of a Dutch general hospital between April 2009 and April 2015 were included. The patients underwent a standard diagnostic work up including cognitive tests (Cambridge Cognitive Examination, including the Mini Mental State Examination) and brain CT. Vascular risk factors such as hypertension, diabetes mellitus, hyperlipidemia and smoking were assessed. CTs were analyzed for presence and severity (absent, mild, moderate or severe) of BGC. Multivariable logistic regression was used to identify risk factors for BGC and linear regression for the association between BGC and cognitive function. RESULTS: Of the 1992 patients, 40.3% was male. The median age was 80 years and 866 patients (43.5%) had BGC. BGC was associated with female gender (odds ratio (OR) 1.27, 95% confidence interval (CI) 1.06-1.53, p 0.011), and inversely associated with hypertension (OR 0.74, 95% CI 0.60-0.89, p 0.002) and use of antihypertensive drugs (OR 0.79, 95% CI 0.64-0.98, p 0.031). No association was found between presence and severity of BGC and cognitive function or other vascular risk factors. CONCLUSIONS: No association with cognitive function was found. Risk factors for BGC were female gender, while hypertension and antihypertensive drug use were associated with a lower risk of BGC.

Prevalence and Association of Basal Ganglia Calcifications and Depressive Symptoms in Patients With Mild Cognitive Impairment or Dementia.

AIM: The aim of this study is to investigate the association between basal ganglia calcification (BGC) and depressive symptoms within older adults with mild cognitive impairment (MCI) or dementia. METHODS: For this cross-sectional study, we included patients with MCI or dementia who visited the memory clinic between April 2009 and April 2015. All patients underwent a standard diagnostic workup, including assessment of depressive symptoms with the Geriatric Depression Scale and computed tomography imaging of the brain. Computed tomography scans were assessed for presence and severity of BGC. To analyse the association between BGC and depressive symptoms, binary logistic regression models were performed with adjustment for age, sex, cardiovascular risk factors, and cardiovascular diseases. RESULTS: In total, 1054 patients were included (median age: 81.0 y; 39% male). BGC was present in 44% of the patients, of which 20% was classified as mild, 20% as moderate, and 4% as severe. There were 223 patients (21%) who had a Geriatric Depression Scale score indicative of depressive symptoms. No association was found between the presence or severity of BGC and depressive symptoms. CONCLUSIONS: Although both BGC and depressive symptoms were common in patients with MCI or dementia, no association was demonstrated between the presence or severity of BGC and depressive symptoms.

Intracranial artery calcifications: Risk factors and association with cardiovascular disease and cognitive function.

BACKGROUND AND AIMS: we know little about clinical outcomes of arterial calcifications. This study investigates the risk factors of intracranial artery calcifications and its association with cardiovascular disease and cognitive function. METHODS: patients were recruited from a Dutch memory clinic, between April 2009 and April 2015. The intracranial internal carotid artery (iICA) and basilar artery were analysed on the presence of calcifications. Calcifications in the iICA were also assessed on severity and location in the tunica intima or tunica media. Using logistic regression, risk factors of intracranial artery calcifications were analysed, as well as the association of these calcifications with cardiovascular disease, cognitive function and type of cognitive disorder (including subjective cognitive impairment, mild cognitive impairment and dementia). Cognitive function was assessed with the Cambridge Cognitive Examination. RESULTS: 1992 patients were included (median age: 78.2 years, ±40% male). The majority of patients had calcifications in the iICA (±95%). Basilar artery calcifications were less prevalent (±8%). Risk factors for cerebral intracranial calcifications were age (p < 0.001), diabetes mellitus (medial iICA, p = 0.004), hypertension (intimal iICA, p < 0.001) and basilar artery, p = 0.019) and smoking (intimal iICA, p = 0.008). iICA calcifications were associated with stroke and intimal calcifications also with myocardial infarction. Intracranial artery calcifications were not associated with cognitive function or type of cognitive disorder. CONCLUSION: the majority of memory clinic patients had intracranial artery calcifications. Cardiovascular risk factors are differentially related to medial or intimal iICA calcifications. iICA calcifications were associated with myocardial infarction and stroke, but not with cognitive outcomes.

What patients want to know, and what we actually tell them: The ABIDE project.

BACKGROUND: We studied to what degree and at whose initiative 25 informational topics, formerly identified as important, are discussed in diagnostic consultations. METHODS: Audio recordings of clinician-patient consultations of 71 patients and 32 clinicians, collected in eight Dutch memory clinics, were independently content-coded by two coders. The coding scheme encompassed 25 informational topics. RESULTS: Approximately half (Mdn = 12) of the 25 topics were discussed per patient during the diagnostic process, with a higher frequency among individuals receiving a dementia diagnosis (Mdn = 14) compared to others (Mdn = 11). Individual topics ranged from being discussed with 2/71 (3%) to 70/71 (99%) of patients. Patients and/or care partners rarely initiated topic discussion (10%). When they did, they often enquired about one of the least frequently addressed topics. CONCLUSION: Most patients received information on approximately half of the important informational topics. Providing the topic list to patients and care partners beforehand could allow consultation preparation and stimulate participation.

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".

Communicating uncertainties when disclosing diagnostic test results for (Alzheimer's) dementia in the memory clinic: The ABIDE project.

BACKGROUND: The development of novel diagnostics enables increasingly earlier diagnosis of Alzheimer's disease (AD). Timely diagnosis may benefit patients by reducing their uncertainty regarding the cause of symptoms, yet does not always provide patients with the desired certainty. OBJECTIVE: To examine, using both quantitative and qualitative methods, uncertainty communicated by memory clinic clinicians in post-diagnostic testing consultations with patients and their caregivers. METHODS: First, we identified all uncertainty expressions of 22 clinicians in audiotaped post-diagnostic testing consultations with 78 patients. Second, we statistically explored relationships between patient/clinician characteristics and uncertainty expressions. Third, the transcribed uncertainty expressions were qualitatively analysed, determining the topic to which they pertained, their source and initiator/elicitor (clinicians/patients/caregivers). RESULTS: Within 57/78 (73%) consultations, clinicians expressed in total 115 uncertainties, of which 37% elicited by the patient or caregiver. No apparent relationships were found between patient/clinician characteristics and whether or not, and how often clinicians expressed uncertainty. Uncertainty expressions pertained to ten different topics, most frequently patient's diagnosis and symptom progression. Expressed uncertainty was mostly related to the unpredictability of the future and limits to available knowledge. DISCUSSION AND CONCLUSIONS: The majority of clinicians openly discussed the limits of scientific knowledge and diagnostic testing with patients and caregivers in the dementia context. Noticeably, clinicians did not discuss uncertainty in about one quarter of consultations. More evidence is needed on the beneficial and/or harmful effects on patients of discussing uncertainty with them. This knowledge can be used to support clinicians to optimally convey uncertainty and facilitate patients' uncertainty management.

Diagnostic performance of Elecsys immunoassays for cerebrospinal fluid Alzheimer's disease biomarkers in a nonacademic, multicenter memory clinic cohort: The ABIDE project.

INTRODUCTION: We compared the automated Elecsys and manual Innotest immunoassays for cerebrospinal fluid (CSF) Alzheimer's disease biomarkers in a multicenter diagnostic setting. METHODS: We collected CSF samples from 137 participants in eight local memory clinics. Amyloid ß(1-42) (Aß42), total tau (t-tau), and phosphorylated tau (p-tau) were centrally analyzed with Innotest and Elecsys assays. Concordances between methods were assessed. RESULTS: Biomarker results strongly correlated between assays with Spearman's ρ 0.94 for Aß42, 0.98 for t-tau, and 0.98 for p-tau. Using Gaussian mixture modeling, cohort-specific cut-points were estimated at 1092 pg/mL for Aß42, 235 pg/mL for t-tau, and 24 pg/mL for p-tau. We found an excellent concordance of biomarker abnormality between assays of 97% for Aß42 and 96% for both t-tau and p-tau. DISCUSSION: The high concordances between Elecsys and Innotest in this nonacademic, multicenter cohort support the use of Elecsys for CSF Alzheimer's disease diagnostics and allow conversion of results between methods.

Hippocampal Calcifications: Risk Factors and Association with Cognitive Function.

Purpose To identify risk factors for hippocampal calcifications and to investigate the association between hippocampal calcifications and cognitive function. Materials and Methods For this retrospective study, consecutive patients visiting a memory clinic at a Dutch general hospital between April 2009 and April 2015 were identified. All individuals underwent a standard diagnostic work-up including cognitive tests and brain CT. The following vascular risk factors were assessed: hypertension, diabetes mellitus, hyperlipidemia, and smoking. Cognitive screening consisted of the Cambridge Cognitive Examination, which includes the Mini-Mental State Examination. CT scans were analyzed for the presence and severity (absent, mild, moderate, severe) of hippocampal calcifications. One measure per patient, only the most severe score, was used. Logistic regression was used to identify risk factors for hippocampal calcifications, and linear regression was used for the association between hippocampal calcifications (patient level) and cognitive function. Results A total of 1991 patients (mean age, 78 years; range, 45-96 years) were included. The mean age of women was 79 years (range, 47-96 years), and the mean age of men was 77 years (range, 45-95 years). Of the 1991 patients, 380 (19.1%) had hippocampal calcifications. Older age (odds ratio [OR] per year, 1.05; 95% confidence interval [CI]: 1.03, 1.06), diabetes mellitus (OR, 1.50; 95% CI: 1.12, 2.00), and smoking (OR, 1.49; 95% CI: 1.05, 2.10) were associated with the presence of hippocampal calcifications. No associations were found between presence and severity of hippocampal calcifications and cognitive function. Conclusion Older age, diabetes mellitus, and smoking were associated with an increased risk of hippocampal calcifications. A greater degree of hippocampal calcifications was not associated with lower cognitive function in patients with memory complaints.

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.

Patients' and caregivers' views on conversations and shared decision making in diagnostic testing for Alzheimer's disease: The ABIDE project.

INTRODUCTION: This study aims to assess patients' and caregivers' views on and experiences with (1) decisions about diagnostic testing for Alzheimer's disease (AD) and (2) receiving test results. METHODS: We conducted separate focus groups with patients from three hospitals who underwent diagnostic testing for AD (N = 11) and their caregivers (N = 11). Audio recordings were transcribed verbatim and analyzed using MaxQDA. RESULTS: Patients and caregivers preferred and perceived active involvement in decision making, but the decision to initiate diagnostic testing seems to be made before the clinician-patient encounter. Patients and caregivers indicate that decisions are driven by a strong need to explain the patient's symptoms. They missed information on why different diagnostic tests were used, what the results of these tests were, and to what extent these results were (ab)normal. DISCUSSION: The decision-making process around diagnostic testing for AD and the information provision before and after diagnostic testing could be improved.

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.