Multimer Detection System-Oligomerized Amyloid Beta (MDS-OAß): A Plasma-Based Biomarker Differentiates Alzheimer's Disease from Other Etiologies of Dementia.

With emerging amyloid therapies, documentation of the patient's amyloid status to confirm the etiology of a clinical diagnosis is warranted prior to instituting amyloid-based therapy. The Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß) is a noninvasive blood-based biomarker utilized to measure Aß oligomerization tendency. We determined the difference in MDS-OAß ratio across the groups: (a) no cognitive impairment or subjective cognitive impairment (NCI/SCI), (b) Alzheimer's disease (AD), (c) non-AD, and (d) mixed Alzheimer's disease-Vascular dementia (AD-VaD). MDS-OAß level was not significantly different between AD and mixed AD-VaD, but both groups were significantly different from the NCI/SCI and from the non-AD group. An MDS-OAß level of >1 could potentially indicate clinical variants of AD or mixed pathology (AD-VaD).

Age Moderates Associations of Hypertension, White Matter Hyperintensities, and Cognition.

BACKGROUND: Hypertension and white matter hyperintensities (WMH) are mutually associated risk factors for cognitive impairment. However, age may modify the associations between hypertension and WMH, and their links to cognitive impairment. OBJECTIVE: We evaluated the interaction between age and hypertension on WMH, and the age-stratified associations of hypertension and WMH with cognition. METHODS: Key measures include systolic blood pressure (SBP), WMH (modified Fazekas visual ratings of cranial MRI), and the Montreal Cognitive Assessment (MoCA). Participants (N = 488) with prodromal and mild dementia were age-stratified (≤49, 50-59, 60-69,≥70), and considered hypertensive if their SBP≥140 mmHg. The interaction between age strata and hypertension on WMH, and age-stratified associations of hypertension and WMH with cognition, were evaluated using multiple linear regression analyses. Analyses controlled for other risk factors for WMH and cognitive impairment. RESULTS: Age moderated the association between SBP and WMH. Hypertension was associated with higher WMH only in those aged 60-69, and WMH trends across age bands differed between those with and without hypertension. Finally, WMH and SBP≥140 were independently associated with lower MoCA scores within the 50-59 age band, while WMH alone was associated with poorer MoCA scores in the≥70 age band. CONCLUSION: In adults with prodromal or mild dementia, hypertension was associated with WMH specifically in the 60-69 age strata. Associations between hypertension and WMH with poorer cognition also differed across age bands. Future studies will be needed to investigate whether blood pressure management to slow cognitive decline by targeting WMH may be age dependent.

The role of cerebral microbleeds in the incidence of post-stroke dementia.

Microbleeds are a marker of cerebrovascular disease however its role in incident post-stroke dementia (PSD) remains unclear. We investigated whether microbleeds are associated with incident PSD, domain-specific cognitive impairment and cognitive decline over a 2-year follow-up; and whether microbleeds interact with acute stroke-related infarcts to synergistically affect cognitive outcomes. In a cohort of patients with first-episode mild ischemic stroke and no pre-stroke dementia, we found patients with 3 or more mixed microbleeds (presence of both lobar and deep) were 4 times more at risk of developing PSD compared to patients with no microbleeds. Patients with strictly lobar microbleeds were 10 times more at risk of developing memory impairment while patients with possible CAA-related microbleeds were 8 times more at risk of developing memory impairment compared to patients with no microbleeds. Microbleeds did not predict cognitive decline at the 2-year follow-up. Acute stroke infarcts were not related to any cognitive outcomes. Microbleeds did not interact with stroke infracts to synergistically affect cognitive outcomes. Our findings suggest that the combined effect of possible CAA and hypertension-related microbleeds play a large and direct role in incident PSD. Management of vasculopathy and amyloid deposition may positively impact cognitive outcomes after stroke.

Autosomal Dominant Frontotemporal Lobar Degeneration in a Filipino Family with Progranulin Mutation.

BACKGROUND: Compared to Western populations, familial frontotemporal lobar degeneration (FTLD) is rare among Asians. Progranulin (GRN) gene mutation, which is a major cause of FTLD, is likewise rare. We present a family with FTLD from the Philippines with an autosomal dominant pattern of inheritance and GRN mutation and briefly review reports of GRN mutations in Asia. CASE PRESENTATION: The proband is 66 years old with progressive nonfluent aphasia (PNFA)-corticobasal syndrome . We assessed 3 generations of her pedigree and found 11 affected relatives with heterogenous phenotypes, usually behavioral variant frontotemporal dementia (FTD) and PNFA. Neuroimaging showed atrophy and hypometabolism consistent with FTD syndromes. White matter hyperintensities were seen in affected members even in the absence of vascular risk factors. A GRN mutation R110X was found in 6 members, 3 with symptoms and 3 were asymptomatic. Plasma GRN was low (<112 ng/mL) in all mutation carriers. No mutations were found in microtubule-associated protein tau, APP, PSEN1, and PSEN2 genes, and all were APOE3. CONCLUSION: This is the first Filipino family with autosomal dominant FTD documented with GRN mutation. Identifying families and cohorts would contribute to therapeutic developments in an area with FTD-GRN.