Neuropsychiatric Symptoms as Predictor of Poor Clinical Outcome in Patients With Vascular Cognitive Impairment.

OBJECTIVE: Examine the association between neuropsychiatric symptoms (NPS) and clinical outcome in memory clinic patients with vascular brain injury. DESIGN/SETTING: TRACE-VCI prospective memory clinic cohort with follow-up (2.1 ± 0.5 years). PARTICIPANTS: Five hundred and seventy-five memory clinic patients with vascular brain injury on MRI (i.e. possible Vascular Cognitive Impairment [VCI]). Severity of cognitive impairment ranged from no objective cognitive impairment to mild cognitive impairment (MCI) and dementia. MEASUREMENTS: We used Neuropsychiatric Inventory (total score and score on hyperactive, psychotic, affective, and apathetic behavior domains) to measure NPS. We assessed the association between NPS and institutionalization, mortality and cognitive deterioration (increase ≥0.5 on Clinical Dementia Rating scale) with Cox proportional hazards models and logistic regression analyses. RESULTS: NPS were present in 89% of all patients, most commonly in the hyperactive and apathetic behavior domain. Across the whole cohort, affective behavior was associated with institutionalization (HR: 1.98 [1.01-3.87]), mainly driven by the dementia subgroup (HR: 2.06 [1.00-4.21]). Apathetic behavior was associated with mortality and cognitive deterioration (HR: 2.07 [1.10-3.90],OR: 1.67 [1.12-2.49], respectively), mainly driven by the MCI subgroup (HR: 4.93 [1.07-22.86],OR: 3.25 [1.46-7.24], respectively). Conversely, hyperactive behavior was related to lower mortality (HR: 0.54 [0.29-0.98]), again particularly driven by the MCI subgroup (HR:0.17 [0.04-0.75]). Psychotic behavior was associated with cognitive deterioration in patients with no objective cognitive impairment (OR: 3.10 [1.09-8.80]) and with institutionalization in MCI (HR: 12.45 [1.28-121.14]). CONCLUSION: NPS are common and have prognostic value in memory clinic patients with possible VCI. This prognostic value depends on the severity of cognitive impairment.

Occurrence of Impaired Physical Performance in Memory Clinic Patients With Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD) occurs often in memory clinic patients. Apart from cognitive deficits, these patients can express physical decline, which predicts adverse health outcomes. In this study, we investigated the cooccurrence of clinically relevant impairments in physical performance and CSVD in memory clinic patients. We included 131 patients with vascular brain injury, mild cognitive impairment or Alzheimer disease with available 3T MRI and physical performance scores. CSVD was visually rated according to 3 subtypes and as a total burden score, composed of the presence of white matter hyperintensities (WMH), lacunar infarcts (LI), and cerebral microbleeds (MB). Physical performance was assessed with the Short Physical Performance Battery (SPPB), covering gait speed, balance, and chair stand performance. CSVD markers and impaired physical performance both occurred often. High total CSVD burdens cooccurred with impaired chair stand performances [odds ratio (OR) 2.67; 95% confidence interval (CI) (1.12-6.34)]. WMH cooccurred with impaired SPPB scores (OR, 3.76; 95% CI, 1.68-8.44), impaired gait speeds (OR, 4.11; 95% CI, 1.81-9.31) and impaired chair stand performances (OR, 5.62; 95% CI, 2.29-13.80). In memory clinic patients, high burdens of CSVD, particularly WMH, often cooccur with impairments in physical performance. The presence of WMH should alert clinicians to the presence of these, clinically relevant, physical impairments.

Prediction of poor clinical outcome in vascular cognitive impairment: TRACE-VCI study.

INTRODUCTION: Prognostication in memory clinic patients with vascular brain injury (eg possible vascular cognitive impairment [VCI]) is often uncertain. We created a risk score to predict poor clinical outcome. METHODS: Using data from two longitudinal cohorts of memory clinic patients with vascular brain injury without advanced dementia, we created (n = 707) and validated (n = 235) the risk score. Poor clinical outcome was defined as substantial cognitive decline (change of Clinical Dementia Rating ≥1 or institutionalization) or major vascular events or death. Twenty-four candidate predictors were evaluated using Cox proportional hazard models. RESULTS: Age, clinical syndrome diagnosis, Disability Assessment for Dementia, Neuropsychiatric Inventory, and medial temporal lobe atrophy most strongly predicted poor outcome and constituted the risk score (C-statistic 0.71; validation cohort 0.78). Of note, none of the vascular predictors were retained in this model. The 2-year risk of poor outcome was 6.5% for the lowest (0-5) and 55.4% for the highest sum scores (10-13). DISCUSSION: This is the first, validated, prediction score for 2-year clinical outcome of patients with possible VCI.

Physical Performance in Memory Clinic Patients: The Potential Role of the White Matter Network.

BACKGROUND/OBJECTIVES: Memory clinic patients commonly also have declined physical performance. This may be attributable to white matter injury, due to vascular damage or neurodegeneration. Quantifying white matter injury is made possible by new magnetic resonance imaging (MRI) techniques, including diffusion-weighted imaging (DWI) of network connectivity. We investigated whether physical performance in memory clinic patients is related to white matter network connectivity. DESIGN: Observational cross-sectional study. SETTING: Memory clinic. PARTICIPANTS: Patients referred to a memory clinic with vascular brain injury on MRI (n = 90; average age = 72 years; 60% male; 34% with diagnosis Alzheimer disease). MEASUREMENTS: We reconstructed structural brain networks from DWI with fiber tractography and used graph theory to calculate global efficiency, fractional anisotropy (FA), and mean diffusivity (MD) of the white matter, and nodal strength (mean FA or MD of all white matter tracts connected to a node). Assessment of physical performance included gait speed, chair stand time, and Short Physical Performance Battery (SPPB) score. RESULTS: Lower global efficiency, lower FA, and higher MD correlated with poorer gait speed, SPPB scores, and chair stand times (R range = 0.23-0.42). Global efficiency and FA explained 5% to 16% of the variance in gait speed, chair stand times, and SPPB scores, independent of age and sex. Moreover, global efficiency and FA explained an additional 4% to 5% of variance on top of lacunar infarcts and white matter hyperintensities. Regional analyses showed that, in particular, the connectivity strength of prefrontal, occipital, striatal, and thalamic nodes correlated with gait speed. CONCLUSION: Poorer physical performance is related to disrupted white matter network connectivity in memory clinic patients with vascular brain injury. The associations of these network abnormalities are partially independent of visible vascular injury. J Am Geriatr Soc 67:1880-1887, 2019.

Association of Amyloid Positron Emission Tomography With Changes in Diagnosis and Patient Treatment in an Unselected Memory Clinic Cohort: The ABIDE Project.

Importance: Previous studies have evaluated the diagnostic effect of amyloid positron emission tomography (PET) in selected research cohorts. However, these research populations do not reflect daily practice, thus hampering clinical implementation of amyloid imaging. Objective: To evaluate the association of amyloid PET with changes in diagnosis, diagnostic confidence, treatment, and patients' experiences in an unselected memory clinic cohort. Design, Setting, and Participants: Amyloid PET using fluoride-18 florbetaben was offered to 866 patients who visited the tertiary memory clinic at the VU University Medical Center between January 2015 and December 2016 as part of their routine diagnostic dementia workup. Of these patients, 476 (55%) were included, 32 (4%) were excluded, and 358 (41%) did not participate. To enrich this sample, 31 patients with mild cognitive impairment from the University Medical Center Utrecht memory clinic were included. For each patient, neurologists determined a preamyloid and postamyloid PET diagnosis that existed of both a clinical syndrome (dementia, mild cognitive impairment, or subjective cognitive decline) and a suspected etiology (Alzheimer disease [AD] or non-AD), with a confidence level ranging from 0% to 100%. In addition, the neurologist determined patient treatment in terms of ancillary investigations, medication, and care. Each patient received a clinical follow-up 1 year after being scanned. Main Outcomes and Measures: Primary outcome measures were post-PET changes in diagnosis, diagnostic confidence, and patient treatment. Results: Of the 507 patients (mean [SD] age, 65 (8) years; 201 women [39%]; mean [SD] Mini-Mental State Examination score, 25 [4]), 164 (32%) had AD dementia, 70 (14%) non-AD dementia, 114 (23%) mild cognitive impairment, and 159 (31%) subjective cognitive decline. Amyloid PET results were positive for 242 patients (48%). The suspected etiology changed for 125 patients (25%) after undergoing amyloid PET, more often due to a negative (82 of 265 [31%]) than a positive (43 of 242 [18%]) PET result (P < .01). Post-PET changes in suspected etiology occurred more frequently in patients older (>65 years) than younger (<65 years) than the typical age at onset of 65 years (74 of 257 [29%] vs 51 of 250 [20%]; P < .05). Mean diagnostic confidence (SD) increased from 80 (13) to 89 (13%) (P < .001). In 123 patients (24%), there was a change in patient treatment post-PET, mostly related to additional investigations and therapy. Conclusions and Relevance: This prospective diagnostic study provides a bridge between validating amyloid PET in a research setting and implementing this diagnostic tool in daily clinical practice. Both amyloid-positive and amyloid-negative results had substantial associations with changes in diagnosis and treatment, both in patients with and without dementia.

Differences between left- and right-sided neglect revisited: A large cohort study across multiple domains.

Unilateral spatial neglect (USN) is a syndrome that can occur after right- and left-hemisphere damage. It is generally accepted that left-sided USN is more severe than right-sided USN. Evidence for such a difference in other domains is lacking. Primary aims were to compare frequency, severity, region specificity, cognition, physical functioning, and physical independence between left and right USN. Secondary aims were to compare lesion characteristics. A total of 335 stroke patients admitted for inpatient rehabilitation were included. The severity of the lateralized attentional deficit was measured with a shape cancellation and line bisection test (in peripersonal and extrapersonal space) and the Catherine Bergego scale. The Mini-Mental State Examination, Stichting Afasie Nederland score, search organization (i.e., best R and intersections rate), Motricity Index, balance, mobility, and self-care were assessed. Measures were statistically compared between left, right, and no USN patients. Lesion overlay plots were compared with lesion subtraction analyses. RESULTS: Left USN (15.82%) was more frequent than right USN (9.25%). Demographic and stroke characteristics were comparable between groups. The lateralized attentional deficit was most severe in left USN. USN in both peripersonal and extrapersonal space was more frequently left-sided in nature. Search efficiency was lower in left USN. Balance was poorer in right USN. No differences between left and right USN were found for cognitive ability, communication, motor strength, mobility, and self-care. Most patients with left USN had right-hemispheric lesions, whereas patients with right USN could have lesions in either the left or the right hemisphere. To conclude, left and right USN are both common after stroke. Although the lateralized attention deficit is worse in left than in right USN, consequences at the level of physical functioning and physical independence are largely comparable. From a clinical perspective, it is important to systematically screen for USN, both after right- and after left-hemisphere damage.