Diagnostic Performance of Automated MRI Volumetry by icobrain dm for Alzheimer's Disease in a Clinical Setting: A REMEMBER Study.

BACKGROUND: Magnetic resonance imaging (MRI) has become important in the diagnostic work-up of neurodegenerative diseases. icobrain dm, a CE-labeled and FDA-cleared automated brain volumetry software, has shown potential in differentiating cognitively healthy controls (HC) from Alzheimer's disease (AD) dementia (ADD) patients in selected research cohorts. OBJECTIVE: This study examines the diagnostic value of icobrain dm for AD in routine clinical practice, including a comparison to the widely used FreeSurfer software, and investigates if combined brain volumes contribute to establish an AD diagnosis. METHODS: The study population included HC (n = 90), subjective cognitive decline (SCD, n = 93), mild cognitive impairment (MCI, n = 357), and ADD (n = 280) patients. Through automated volumetric analyses of global, cortical, and subcortical brain structures on clinical brain MRI T1w (n = 820) images from a retrospective, multi-center study (REMEMBER), icobrain dm's (v.4.4.0) ability to differentiate disease stages via ROC analysis was compared to FreeSurfer (v.6.0). Stepwise backward regression models were constructed to investigate if combined brain volumes can differentiate between AD stages. RESULTS: icobrain dm outperformed FreeSurfer in processing time (15-30 min versus 9-32 h), robustness (0 versus 67 failures), and diagnostic performance for whole brain, hippocampal volumes, and lateral ventricles between HC and ADD patients. Stepwise backward regression showed improved diagnostic accuracy for pairwise group differentiations, with highest performance obtained for distinguishing HC from ADD (AUC = 0.914; Specificity 83.0%; Sensitivity 86.3%). CONCLUSION: Automated volumetry has a diagnostic value for ADD diagnosis in routine clinical practice. Our findings indicate that combined brain volumes improve diagnostic accuracy, using real-world imaging data from a clinical setting.

Practices and opinions about disclosure of the diagnosis of Alzheimer's disease to patients with MCI or dementia: a survey among Belgian medical experts in the field of dementia.

Previous surveys revealed that only a minority of clinicians routinely disclosed the diagnosis of Alzheimer's disease (AD) to their patients. Many health professionals fear that the disclosure could be harmful to the patient. Recent advances in the development of biomarkers and new diagnostic criteria allow for an earlier diagnosis of AD at the mild cognitive impairment (MCI) stage. The Belgian Dementia Council, a group of Belgian experts in the field of dementia, performed a survey among its 44 members about their opinions and practices regarding disclosure of the diagnosis of AD, including MCI due to AD, and its consequences. Twenty-six respondents declared that they often or always disclose the diagnosis of AD to patients with dementia and to patients with MCI when AD CSF biomarkers are abnormal. The majority observed that the disclosure of AD is rarely or never harmful to the patients. Their patients and their caregivers rarely or never demonstrated animosity towards the clinicians following disclosure of the diagnosis of AD. These results should reassure clinicians about the safety of AD diagnosis disclosure in most cases whether the patient is at the MCI or the dementia stage.

Dementia, End of Life, and Euthanasia: A Survey Among Dementia Specialists Organized by the Belgian Dementia Council.

BACKGROUND: Palliative care and Advance Care Planning (ACP) are increasingly recommended for an optimal management of late-stage dementia. In Belgium, euthanasia has been decriminalized in 2002 for patients who are "mentally competent" (interpreted as non-demented). It has been suggested that advance directives for euthanasia (ADE) should be made possible for dementia patients. OBJECTIVE: This study presents the results of an internet survey among Belgian dementia specialists. METHODS: In 2013, the Belgian Dementia Council (BeDeCo) organized a debate on end of life decisions in dementia. Participants were medical doctors who are specialists in the dementia field. After the debate, an anonymous internet survey was organized. The participation rate was 55%. The sample was representative of the BeDeCo members. RESULTS: The results showed consensus in favor of palliative care and ACP, although ACP is not systematically addressed in practice. Few patients with dementia have requested euthanasia, but for those who did the participants had agreed to implement it for some patients. A majority of participants (94%) believe that most patients and their families are poorly informed about euthanasia. Although most participants (77%) said they approved the Law on euthanasia, 65% said they were against an extension of the Law to allow ADE for dementia. CONCLUSION: Palliative care and ACP are clearly accepted by professionals, although a gap between recommendation and practice remain. Euthanasia is a much more debated issue, even if a majority of professionals are, in principle, in favor of the current Law and seem to disapprove with a Law change allowing ADE for dementia. A better education for both health professionals and the lay public will be a key element in the future.

Factors Associated with the Caregivers' Desire to Institutionalize Persons with Dementia: A Cross-Sectional Study.

BACKGROUND/AIMS: Dementia is one of the main reasons for institutionalization among the elderly. Few studies have explored factors associated with the caregivers' (CG) desire to institutionalize (DTI) a person with dementia (PWD). The objective of this study is to identify modifiable and non-modifiable psychosocial and sociodemographic factors associated with a caregiver's DTI. METHODS: Cross-sectional data of 355 informal CG of community-dwelling PWD were analyzed. Several characteristics were identified in CG and PWD to be included in a multivariable regression model based on the purposeful selection method. RESULTS: Positively modifiable associated factors were: higher CG burden, being affected by behavioral problems, and respite care use. Positively associated non-modifiable factors were: CG older age, being professionally active, and CG higher educational level. Cohabitation and change of professional situation were negatively associated. CONCLUSION: Although no causality can be assumed, several practical recommendations can be suggested. First of all, these results reconfirm the importance of multicomponent strategies, especially support aimed at decreasing burden and in learning coping strategies. Also, CG might benefit from information about support options, such as respite care services. Finally, special attention should be given to older and working CG. In the latter, flexible and adaptive working conditions might alleviate burden and therefore reduce the DTI of the PWD.

Vulnerability of caregivers of people with a neurodegenerative disease: a synthesis.

The aging of the population and the increasing of the neurodegenerative pathologies encourage the current policies in health to further promote the home maintenance for dependent elderly people. Therefore, informal caregivers provide a substantial assistance to the medical team by monitoring home care. These volunteer caregivers who play an essential role in the survival of our health system however may expose to dangers of systematic assistance. In order to better understand the plural risks which caregivers are likely to face, this paper proposes a critical analysis of the consequences of caregiving on health and quality of life and summarizes factors that contribute to vulnerability - protection of caregivers. It seems caregivers will present very heterogeneous reactions in the way they are considering the care situation. Facing to many difficulties encountered, caregivers are dealing with their skills and adopt personal coping strategies. There is thus a wide range of fragility profiles and needs among caregivers. Better taking into account the multiple components of aid relationships paves the way toward possible new care perspectives by recognizing the specific needs of each caregiver with respect for its uniqueness. In this way only, we can effectively contribute to challenge one of the important and actual social issue: the prevention of global exhaustion of caregivers of people with neurodegenerative disease.

A Retrospective Belgian Multi-Center MRI Biomarker Study in Alzheimer's Disease (REMEMBER).

BACKGROUND: Magnetic resonance imaging (MRI) acquisition/processing techniques assess brain volumes to explore neurodegeneration in Alzheimer's disease (AD). OBJECTIVE: We examined the clinical utility of MSmetrix and investigated if automated MRI volumes could discriminate between groups covering the AD continuum and could be used as a predictor for clinical progression. METHODS: The Belgian Dementia Council initiated a retrospective, multi-center study and analyzed whole brain (WB), grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), cortical GM (CGM) volumes, and WM hyperintensities (WMH) using MSmetrix in the AD continuum. Baseline (n = 887) and follow-up (FU, n = 95) T1-weighted brain MRIs and time-linked neuropsychological data were available. RESULTS: The cohort consisted of cognitively healthy controls (HC, n = 93), subjective cognitive decline (n = 102), mild cognitive impairment (MCI, n = 379), and AD dementia (n = 313). Baseline WB and GM volumes could accurately discriminate between clinical diagnostic groups and were significantly decreased with increasing cognitive impairment. MCI patients had a significantly larger change in WB, GM, and CGM volumes based on two MRIs (n = 95) compared to HC (FU>24months, p = 0.020). Linear regression models showed that baseline atrophy of WB, GM, CGM, and increased CSF volumes predicted cognitive impairment. CONCLUSION: WB and GM volumes extracted by MSmetrix could be used to define the clinical spectrum of AD accurately and along with CGM, they are able to predict cognitive impairment based on (decline in) MMSE scores. Therefore, MSmetrix can support clinicians in their diagnostic decisions, is able to detect clinical disease progression, and is of help to stratify populations for clinical trials.

Alzheimer's disease and driving: review of the literature and consensus guideline from Belgian dementia experts and the Belgian road safety institute endorsed by the Belgian Medical Association.

Alzheimer's disease (AD) is a highly prevalent condition and its prevalence is expected to further increase due to the aging of the general population. It is obvious that the diagnosis of AD has implications for driving. Finally, driving discussions are also emotionally charged because driving is associated with independence and personal identity. However, it is not clear how to implement this in clinical practice and the Belgian law on driving is rather vague in its referral to neurodegenerative brain diseases in general nor does it provide clear-cut instructions for dementia or AD compared to for example driving for patients with epilepsy and as such does not prove to be very helpful. The present article reviews what is known from both literature and existing guidelines and proposes a consensus recommendation tailored to the Belgian situation agreed by both AD experts and the Belgian Road Safety Institute endorsed by the Belgian Medical Association. It is concluded that the decision about driving fitness should be considered as a dynamic process where the driving fitness is assessed and discussed early after diagnosis and closely monitored by the treating physician. The diagnosis of AD on itself definitely does not imply the immediate and full revocation of a driving license nor does it implicate a necessary referral for a formal on-road driving assessment. There is no evidence to recommend a reduced exposure or a mandatory co-pilot. A MMSE-based framework to trichotomise AD patients as safe, indeterminate or unsafe is presented. The final decision on driving fitness can only be made after careful history taking and clinical examination, neuropsychological, functional and behavioral evaluation and, only for selected cases, a formal assessment of driving performance.

POLG2 deficiency causes adult-onset syndromic sensory neuropathy, ataxia and parkinsonism.

OBJECTIVE: Mitochondrial dysfunction plays a key role in the pathophysiology of neurodegenerative disorders such as ataxia and Parkinson's disease. We describe an extended Belgian pedigree where seven individuals presented with adult-onset cerebellar ataxia, axonal peripheral ataxic neuropathy, and tremor, in variable combination with parkinsonism, seizures, cognitive decline, and ophthalmoplegia. We sought to identify the underlying molecular etiology and characterize the mitochondrial pathophysiology of this neurological syndrome. METHODS: Clinical, neurophysiological, and neuroradiological evaluations were conducted. Patient muscle and cultured fibroblasts underwent extensive analyses to assess mitochondrial function. Genetic studies including genome-wide sequencing were conducted. RESULTS: Hallmarks of mitochondrial dysfunction were present in patients' tissues including ultrastructural anomalies of mitochondria, mosaic cytochrome c oxidase deficiency, and multiple mtDNA deletions. We identified a splice acceptor variant in POLG2, c.970-1G>C, segregating with disease in this family and associated with a concomitant decrease in levels of POLG2 protein in patient cells. INTERPRETATION: This work extends the clinical spectrum of POLG2 deficiency to include an overwhelming, adult-onset neurological syndrome that includes cerebellar syndrome, peripheral neuropathy, tremor, and parkinsonism. We therefore suggest to include POLG2 sequencing in the evaluation of ataxia and sensory neuropathy in adults, especially when it is accompanied by tremor or parkinsonism with white matter disease. The demonstration that deletions of mtDNA resulting from autosomal-dominant POLG2 variant lead to a monogenic neurodegenerative multicomponent syndrome provides further evidence for a major role of mitochondrial dysfunction in the pathomechanism of nonsyndromic forms of the component neurodegenerative disorders.

Clinical utility and applicability of biomarker-based diagnostic criteria for Alzheimer's disease: a BeDeCo survey.

We conducted a survey regarding the medical care of patients with dementia in expert settings in Belgium. Open, unrestricted and motivated answers were centralized, blindly interpreted and structured into categories. The report of the results was then submitted to the participants in subsequent plenary meetings and through email. Fourteen experts responded to the questionnaire, confirming that recent propositions to modify Alzheimer's disease (AD) diagnostic criteria and options have stirred up debate among well-informed and dedicated experts in the field. The opinions were not unanimous and illustrate how difficult it is to find a standardized method of diagnosing this disease. The responses to the survey suggest that application of a step-by-step pragmatic method is used in practice. Only when the combination of clinical findings and classical structural neuro-imaging is insufficient for a diagnosis or suggests an atypical presentation, additional biomarkers are considered. Interestingly, few differences, if any, were observed between the use of biomarkers in MCI and in AD. In conclusion, the Belgian experts consulted in this survey were generally in agreement with the new diagnostic criteria for AD, although some concern was expressed about them being too "amyloidocentric". Although the clinical examination, including a full neuropsychological evaluation, is still considered as the basis for diagnosis, most experts also stated that they use biomarkers to help with diagnosis.

Symptoms of depression and anxiety after the disclosure of the diagnosis of Alzheimer disease.

BACKGROUND AND PURPOSE: Many people fear that the disclosure of the diagnosis of Alzheimer disease (AD) to patients will prompt depressive symptoms or catastrophic reactions. We aimed to prospectively evaluate the modification of anxiety and depressive symptoms 3 months after the disclosure of the diagnosis of AD. METHODS: A total of 100 consecutive newly diagnosed patients with AD (mild or moderate stage) and their caregivers were included. The evolution of symptoms of depression and anxiety was assessed with the Zung Self-Rating Depression Scale (Zung SDS) and the depression item of the Neuropsychiatric Inventory (NPI-d) and the anxiety item of the Neuropsychiatric Inventory (NPI-a). After 3 months, the caregivers were asked their opinions on the global effect of the disclosure using a Likert-type scale. RESULTS: At 3 months, there was no significant change in the mean NPI-d (P = .87) and Zung SDS (P = .18) and a significant reduction in the NPI-a (P = .05). The NPI-d worsened in 22% of patients, improved in 22%, and remained unchanged in 56%. The NPI-a worsened in 12% of patients, improved in 33%, and remained unchanged in 54%. The caregivers rated the global effect of the disclosure as negative in 8%, neutral in 71%, and positive in 21% of patients. None of the patients or their proxies reported suicide attempts or catastrophic reactions. CONCLUSIONS: The disclosure of AD is safe in most cases and may improve anxiety. Symptoms of depression and anxiety worsen only in a minority of patients. The fear of depression or catastrophic reaction should not prevent clinicians to disclose the diagnosis of AD.

Validity of the five-word test for the evaluation of verbal episodic memory and dementia in a memory clinic setting.

BACKGROUND: The five-word test (FWT) uses semantic clues to optimize the encoding and retrieval of 5 items. Our objective was to assess the validity of the FWT as a measure of episodic memory when compared with the Free and Cued Selective Reminding Test (FCSRT), and its ability to distinguish participants with any dementia and especially Alzheimer disease (AD) from those with only subjective complaints. METHODS: Two hundred participants with Mini-Mental State Examination (MMSE) >15 were prospectively evaluated. The sum of the immediate and delayed free recalls of the FWT is called the free recall score (FRS). The sum of the immediate free, immediate cued, delayed free, and delayed cued recalls is called the total recall score (TRS). A total weighted score (TWS) is calculated using this formula: (free recalls × 2) + cued recalls. RESULTS: The correlation between FRS and the free recall scores of the FCSRT and between TRS and the total recall scores of the FCSRT was significant (r (s) ranges from .74-.84, P < .001). Area under the receiver--operating characteristic (ROC) curves of the MMSE, FRS, TRS, and TWS were not statistically different. A TWS at a cutoff value ≤15 could discriminate any dementia from subjective complaints with a sensitivity of 75% and a specificity of 95.9% or AD from subjective complaints with a sensitivity of 90.2% and a specificity of 95.9%. CONCLUSION: The FWT is a valid test of verbal episodic memory. It is useful to discriminate dementia especially AD from isolated subjective complaints.

Dissociation between numerosity and duration processing in aging and early Parkinson's disease.

Numerosity and duration processing have been shown to be underlain by a single representational mechanism, namely an accumulator, and to rely on a common cerebral network located principally in areas around the right intraparietal sulcus. However, recent neuropsychological findings reveal a dissociation between numerosity and duration processing, which suggests the existence of partially distinct mechanisms. In this study, we tested the idea of partially common and distinct mechanisms by investigating, for the first time, both numerical and temporal processing abilities in non-demented Parkinson's disease (PD) patients known to suffer from duration impairment and in healthy elderly adults known to have impaired performance in duration tasks. The aim was to assess whether this impaired duration processing would extend to numerosity processing. The participants had to compare either the numerosity of flashed dot sequences or the duration of single dot displays. The results demonstrate an effect of aging on duration comparison, healthy elderly participants making significantly more errors than healthy young participants. Importantly, the performance of PD patients on the duration task was worse than that of the healthy young and elderly groups, whereas no difference was found for numerosity comparison. This dissociation supports the idea that partly independent systems underlie the processing of numerosity and duration.