Therapeutics targeting frontotemporal dementia (FTD) are entering clinical trials. There are challenges to conducting these studies, including the relative rarity of the disease. Remote assessment tools could increase access to clinical research and pave the way for decentralized clinical trials. We developed the ALLFTD Mobile App, a smartphone application that includes assessments of cognition, speech/language, and motor functioning. The objectives were to determine the feasibility and acceptability of collecting remote smartphone data in a multicenter FTD research study and evaluate the reliability and validity of the smartphone cognitive and motor measures.

A diagnostically mixed sample of 207 participants with FTD or from familial FTD kindreds (CDR®+NACC-FTLD=0 [n=91]; CDR®+NACC-FTLD=0.5 [n=39]; CDR®+NACC-FTLD>1 [n=39]; unknown [n=38]) were asked to remotely complete a battery of tests on their smartphones three times over two weeks. Measures included five executive functioning (EF) tests, an adaptive memory test, and participant experience surveys. A subset completed smartphone tests of balance at home (n=31) and a finger tapping test (FTT) in the clinic (n=11). We analyzed adherence (percentage of available measures that were completed) and user experience. We evaluated Spearman-Brown split-half reliability (100 iterations) using the first available assessment for each participant. We assessed test-retest reliability across all available assessments by estimating intraclass correlation coefficients (ICC). To investigate construct validity, we fit regression models testing the association of the smartphone measures with gold-standard neuropsychological outcomes (UDS3-EF composite [Staffaroni et al., 2021], CVLT3-Brief Form [CVLT3-BF] Immediate Recall, mechanical FTT), measures of disease severity (CDR®+NACC-FTLD Box Score & Progressive Supranuclear Palsy Rating Scale [PSPRS]), and regional gray matter volumes (cognitive tests only).

Participants completed 70% of tasks. Most reported that the instructions were understandable (93%), considered the time commitment acceptable (97%), and were willing to complete additional assessments (98%). Split-half reliability was excellent for the executive functioning (r’s=0.93-0.99) and good for the memory test (r=0.78). Test-retest reliabilities ranged from acceptable to excellent for cognitive tasks (ICC: 0.70-0.96) and were excellent for the balance (ICC=0.97) and good for FTT (ICC=0.89). Smartphone EF measures were strongly associated with the UDS3-EF composite (ß's=0.6-0.8, all p<.001), and the memory test was strongly correlated with total immediate recall on the CVLT3-BF (ß=0.7, p<.001). Smartphone FTT was associated with mechanical FTT (ß=0.9, p=.02), and greater acceleration on the balance test was associated with more motor features (ß=0.6, p=0.02). Worse performance on all cognitive tests was associated with greater disease severity (ß's=0.5-0.7, all p<.001). Poorer performance on the smartphone EF tasks was associated with smaller frontoparietal/subcortical volume (ß's=0.4-0.6, all p<.015) and worse memory scores with smaller hippocampal volume (ß=0.5, p<.001).

These results suggest remote digital data collection of cognitive and motor functioning in FTD research is feasible and acceptable. These findings also support the reliability and validity of unsupervised ALLFTD Mobile App cognitive tests and provide preliminary support for the motor measures, although further study in larger samples is required.

Abnormalities in social and emotional behavior are the major diagnostic criteria for behavioral variant frontotemporal dementia (bvFTD). Investigators have attributed their behavioral disturbances to disease in mesial prefrontal and related networks, such as the salience network. This study examined the main neural correlates of informant-reported socioemotional dysfunction among patients with bvFTD compared to those with early-onset (before age 65) Alzheimer's Disease (EOAD).

Participants included 13 patients with bvFTD and their caregivers and 18 patients with EOAD and their caregivers. The caregivers consisted of a spouse, family member, or other informant who resided with the patient. They completed the informant-based Socioemotional Dysfunction Scale (SDS), a 40-item scale which rates common disturbances in social and emotional behavior on a five-point Likert scale (1-5). The patients underwent magnetic resonance imaging (MRI) with tensor-based morphometry (TBM) analysis of the 3D T1-weighted MRI scans. Computations of mean Jacobian values within select regions of interest (ROIs) in frontal and temporal lobes generated numerical summaries of regional volumes, and voxel-wise regressions created 3D statistical maps of the association between tissue volume and SDS total scores. Statistical analyses included independent samples t-tests group differences in ROIs and SDS scores, Pearson correlations between SDS scores and brain volumes, and multiple regression of ROIs with SDS scores and group as predictor variables.

Compared to the EOAD group, the bvFTD group had significantly higher SDS scores (p < .001; d = 2.24), smaller frontal lobe volumes (specifically dorsolateral-prefrontal cortex, p = .003; d = 1.24), and larger temporal lobe volumes (specifically hippocampus, p = .014; d = 0.979). Within the bvFTD group, higher SDS scores were associated with a smaller right anterior temporal lobe (ATL; p = .005; r = -.729), especially the lateral ATLs (p = .002; r = -.776), and a smaller bilateral orbitofrontal cortex (OFC; p = .016; r = -.650). In contrast, within the EOAD group, higher SDS scores were associated with a smaller right parietal cortex (p = .030; r = .542). In the entire sample (both bvFTD and EOAD), higher SDS scores was associated with a smaller lateral ATL volumes (p = .019; r = -.431). Regression analyses confirmed that SDS score predicted lateral ATL volume (p = .041; b = -.262) after controlling for diagnosis (p < .001; b = -.692).

These findings are consistent with greater socioemotional dysfunction, smaller frontal, and larger mesial temporal regions in bvFTD, when compared to EOAD. The findings, however, suggest that positively disturbed socioemotional behavior in bvFTD, as reported by caregivers, results from involvement of the right temporal lobe and the lateral temporal region, with further contribution from disease in OFC. The association of SDS scores and ATL volume across diagnostic groups suggests that this region is instrumental in socioemotional functioning and that the SDS may have diagnostic value in distinguishing the "right-temporal variant" of bvFTD.

Cognitive tests on which performance is unrelated to brain pathology are considered “hold” tests and are often used to estimate cognitive abilities prior to injury or disease. Amongst the most commonly used “hold” tests are measures of irregular word reading, such as the Test of Premorbid Functioning (TOPF). Measures of irregular word reading assess ability to accurately pronounce phonetic irregularities based on prior experience and word knowledge, and tend to be insensitive to most forms of brain pathology (Lezak, 2012). However, research examining whether a relationship exists between neurodegenerative diseases and decline in irregular word reading is limited. The few studies completed have demonstrated a decline in irregular word reading in neurodegenerative disease in general (Berg, Durant, Banks, & Miller, 2016) and Alzheimer’s dementia specifically (McFarlane, Welch, & Rodgers, 2006). However, no known research has been published examining whether irregular word reading and TOPF scores differ depending on cognitive classifications commensurate with DSM-V diagnoses (i.e., mild or major neurocognitive disorder, etc.), or presumed neurological etiology.

Patients were enrolled from the University of Colorado Hospital Neuropsychology Clinic. This study was a retrospective review of consecutive referrals over the age of 65 to the University of Colorado Hospital Neuropsychology Clinic from 2019 to present. The TOPF was administered along with a full neuropsychological battery and patients were clinically classified by severity of cognitive impairment (e.g., Normal, Mild Neurocognitive Disorder, Major Neurocognitive Disorder) and presumed neurologic etiology (e.g., Alzheimer’s disease (AD), Parkinson’s disease (PD), vascular cognitive impairment (VCI), and mixed dementia (AD and VCI). TOPF Raw scores were used for all analyses. Correlation analysis was conducted to determine significant relationships between various demographic variables and TOPF performance. ANCOVA analyses were conducted to examine differences on TOPF performance by diagnostic classification and differences on TOPF performance by presumed neurologic etiology.

Correlation determined a significant relationship between TOPF performance and education (r = .51, p < .001), but not age (p = .092) or gender (p = .680). ANCOVA revealed a significant effect of TOPF performance on diagnostic group classification after controlling for education, F(2, 504)= 26.45, p < .001. Post hoc analysis revealed that those diagnosed with Major Neurocognitive Disorder performed the worst on the TOPF (M=39.801 ± .958), followed by those diagnosed with Mild Neurocognitive Disorder (M= 45.371 ± .767), while those diagnosed as cognitively normal performed the best (M= 49.826 ± .993). Additional ANCOVA analysis revealed a significant effect of TOPF performance on presumed neurologic etiology after controlling for education, F(3,148)=6.07, p = .001. Post hoc analyses revealed that participants with suspected AD (M= 40.728 ± 1.613) and those with suspected VCI (M= 32.804 ± 3.480) performed worse on the TOPF compared to those with suspected PD (M=46.964 ± 1.506), (p=.042 and p = .004, respectively).

Results suggest that TOPF performance in older individuals is sensitive to cognitive impairment. Furthermore, these results suggest that this sensitivity may be further influenced by presumed neurologic etiology. These findings are consistent with prior studies which demonstrated a decline in irregular word reading in individuals with neurodegenerative diseases.

Former professional American football players have a high relative risk for neurodegenerative diseases like chronic traumatic encephalopathy (CTE). Interpreting low cognitive test scores in this population occasionally is complicated by performance on validity testing. Neuroimaging biomarkers may help inform whether a neurodegenerative disease is present in these situations. We report three cases of retired professional American football players who completed comprehensive neuropsychological testing, but “failed” performance validity tests, and underwent multimodal neuroimaging (structural MRI, Aß-PET, and tau-PET).

Three cases were identified from the Focused Neuroimaging for the Neurodegenerative Disease Chronic Traumatic Encephalopathy (FIND-CTE) study, an ongoing multimodal imaging study of retired National Football League players with complaints of progressive cognitive decline conducted at Boston University and the UCSF Memory and Aging Center. Participants were relatively young (age range 55-65), had 16 or more years of education, and two identified as Black/African American. Raw neuropsychological test scores were converted to demographically-adjusted z-scores. Testing included standalone (Test of Memory Malingering; TOMM) and embedded (reliable digit span, RDS) performance validity measures. Validity cutoffs were TOMM Trial 2 < 45 and RDS < 7. Structural MRIs were interpreted by trained neurologists. Aß-PET with Florbetapir was used to quantify cortical Aß deposition as global Centiloids (0 = mean cortical signal for a young, cognitively normal, Aß negative individual in their 20s, 100 = mean cortical signal for a patient with mild-to-moderate Alzheimer’s disease dementia). Tau-PET was performed with MK-6240 and first quantified as standardized uptake value ratio (SUVR) map. The SUVR map was then converted to a w-score map representing signal intensity relative to a sample of demographically-matched healthy controls.

All performed in the average range on a word reading-based estimate of premorbid intellect. Contribution of Alzheimer’s disease pathology was ruled out in each case based on Centiloids quantifications < 0. All cases scored below cutoff on TOMM Trial 2 (Case #1=43, Case #2=42, Case #3=19) and Case #3 also scored well below RDS cutoff (2). Each case had multiple cognitive scores below expectations (z < -2.0) most consistently in memory, executive function, processing speed domains. For Case #1, MRI revealed mild atrophy in dorsal fronto-parietal and medial temporal lobe (MTL) regions and mild periventricular white matter disease. Tau-PET showed MTL tau burden modestly elevated relative to controls (regional w-score=0.59, 72nd%ile). For Case #2, MRI revealed cortical atrophy, mild hippocampal atrophy, and a microhemorrhage, with no evidence of meaningful tau-PET signal. For Case #3, MRI showed cortical atrophy and severe white matter disease, and tau-PET revealed significantly elevated MTL tau burden relative to controls (w-score=1.90, 97th%ile) as well as focal high signal in the dorsal frontal lobe (overall frontal region w-score=0.64, 74th%ile).

Low scores on performance validity tests complicate the interpretation of the severity of cognitive deficits, but do not negate the presence of true cognitive impairment or an underlying neurodegenerative disease. In the rapidly developing era of biomarkers, neuroimaging tools can supplement neuropsychological testing to help inform whether cognitive or behavioral changes are related to a neurodegenerative disease.

White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.

240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.

In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).

These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that can only be diagnosed at post-mortem. Revised criteria for the clinical syndrome of CTE, known as traumatic encephalopathy syndrome (TES), include impairments in episodic memory and/or executive function as core clinical features. These criteria were informed by retrospective interviews with next-of-kin and the presence and rates of objective impairments in memory and executive functions in CTE are unknown. Here, we characterized antemortem neuropsychological test performance in episodic memory and executive functions among deceased contact sport athletes neuropathologically diagnosed with CTE.

The sample included 80 deceased male contact sport athletes from the UNITE brain bank who had autopsy-confirmed CTE (and no other neurodegenerative diseases). Published criteria were used for the autopsy diagnosis of CTE. Neuropsychological test reports (raw scores) were acquired through medical record requests. Raw scores were converted to z-scores using the same age, sex, and education-adjusted normative data. Tests of memory included long delay trials from the Rey Complex Figure, CVLT-II, HVLT-R, RBANS, and BVMT-R. Tests of executive functions included Trail Making Test-B (TMT-B), Controlled Oral Word Association Test, WAIS-III Picture Arrangement, and various WAIS-IV subtests. Not all brain donors had the same tests, and the sample sizes vary across tests, with 33 donors having tests from both domains. Twenty-eight had 1 test in memory and 3 had 2+. Eight had 1 test of executive function and 46 had 2+. A z-score of 1.5 standard deviations below the normative mean was impaired. Interpretation of test performance followed the American Academy of Clinical Neuropsychology guidelines (Guilmette et al., 2020). Bivariate correlations assessed cumulative p-tau burden (summary semiquantitative ratings of p-tau severity across 11 brain regions) and TMT-B (n=34) and CVLT-II (n=14), the most common tests available.

Of the 80 (mean age= 59.9, SD=18.0 years; 13, 16.3% were Black), 72 played football, 4 played ice hockey, and 4 played other contact sports. Most played at the professional level (57, 71.3%). Mean time between neuropsychological testing and death was 3.9 (SD= 4.5) years. The most common reason for testing was dementia-related (43, 53.8%). Mean z-scores fell in the average psychometric range(mean z= -0.52, SD=1.5, range= -6.0 to 3.0) for executive function and the low average range for memory (mean z= -1.3, SD=1.1, range= -4.0 to 2.0). Eleven (20.4%) had impairment on 1 test and 3 (5.6%) on 2+ tests of executive functions. The most common impairment was on TMT-B (mean z= -1.77, 13 [38.2%] impaired). For memory, 13 (41.9%) had impairment on 1 test. Of the 14 who had CVLT-II, 7 were impaired (mean z= -1.33). Greater p-tau burden was associated with worse performance on CVLT-II (r= -.653, p= .02), but not TMT-B (r= .187, p>.05).

This study provides the first evidence for objectively-measured impairments in executive functions and memory in a sample with known, autopsy-confirmed CTE. Furthermore, p-tau burden corresponded to worse memory test performance. Examination of neuropsychological tests from medical records has limitations but can overcome shortcomings of retrospective informant reports to provide insight into the cognitive profiles associated with CTE.

To explore the utility of neuropsychological testing for patients with Primary Progressive Aphasia and compare testing data for a Logopenic and Semantic PPA variants within the medically complex Veteran population.

Both participants were referred by their psychiatrist due to memory concerns. The case studies testing data will be compared to look at the differences on testing between different PPA presentations within the Veteran population. Patient A is a 77 year old, right handed, African American, divorced man with approximately 14 years of formal education. Patient B is a 76 year old, right handed, Caucasian, widowed man with approximately 16 years of formal education.

Patient A displayed problems with single-word retrieval, repetition of nonsense words and sentences, comprehension, reading, spelling, and naming. He also displayed impairments in aspects of working memory, along with learning and memory. His cognitive profile raises concern for a logopenic variant of primary progressive aphasia, which often has Alzheimer's disease pathology. Patient B displayed empty speech, impairments in fluency and reduced semantic knowledge that raises concern for a semantic variant of primary progressive aphasia. However, aspects of his presentation are not consistent with this diagnosis, specifically intact confrontation visual naming. Patient has a history of significant alcohol abuse, although he has mostly remained sober since moving to Texas. This evaluation cannot rule out the contribution of sustained alcohol use on his cognitive functioning; however, this is likely not the primary etiology given his significant language issues.

Patients with medically complex histories and unclear timelines of symptom progressive make it difficult for diagnostic clarity. Diagnoses can be additionally difficult to determine at times when the clinical presentation is not as clearly defined in textbooks. This case study comparison displays the importance of integrating all data to determine the proper diagnosis to optimize patient care and provide recommendations tailored to that individual.

Traumatic brain injury (TBI) and concussion are associated with increased dementia risk. Accurate TBI/concussion exposure estimates are relatively unknown for less common neurodegenerative conditions like frontotemporal dementia (FTD). We evaluated lifetime TBI and concussion frequency in patients diagnosed with a range of FTD spectrum conditions and related prior head trauma to cavum septum pellucidum (CSP) characteristics observable on MRI.

We administered the Ohio State University TBI Identification and Boston University Head Impact Exposure Assessment to 108 patients (age 69.5 ± 8.0, 35% female, 93% white or unknown race) diagnosed at the UCSF Memory and Aging Center with one of the following FTD or related conditions: behavioral variant frontotemporal dementia (N=39), semantic variant primary progressive aphasia (N=16), nonfluent variant PPA (N=23), corticobasal syndrome (N=14), or progressive supranuclear palsy (N=16). Data were also obtained from 217 controls (“HC”; age 76.8 ± 8.0, 53% female, 91% white or unknown race). CSP characteristics were defined based on width or “grade” (0-1 vs. 2+) and length of anterior-posterior separation (millimeters). We first describe frequency of any and multiple (2+) prior TBI based on different but commonly used definitions: TBI with loss of consciousness (LOC), TBI with LOC or posttraumatic amnesia (LOC/PTA), TBI with LOC/PTA or other symptoms like dizziness, nausea, “seeing stars,” etc. (“concussion”). TBI/concussion frequency was then compared between FTD and HC using chi-square. Associations between TBI/concussion and CSP characteristics were analyzed with chi-square (CSP grade) and Mann-Whitney U tests (CSP length). We explored sex differences due to typically higher rates of TBI among males.

History of any TBI with LOC (FTD=20.0%, HC=19.2%), TBI with LOC/PTA (FTD:32.2%, HC=31.5%), and concussion (FTD: 50.0%, HC=44.3%) was common but not different between study groups (p’s>.4). In both FTD and HC, prior TBI/concussion was nominally more frequent in males but not significantly greater than females. Frequency of repeat TBI/concussion (2+) also did not differ significantly between FTD and HC (repeat TBI with LOC: 6.7% vs. 3.3%, TBI with LOC/PTA: 12.2% vs. 10.3%, concussion: 30.2% vs. 28.7%; p’s>.2). Prior TBI/concussion was not significantly related to CSP grade or length in the total sample or within the FTD or HC groups.

TBI/concussion rates depend heavily on the symptom definition used for classifying prior injury. Lifetime symptomatic TBI/concussion is common but has an unclear impact on risk for FTD-related diagnoses. Larger samples are needed to appropriately evaluate sex differences, to evaluate whether TBI/concussion rates differ between specific FTD phenotypes, and to understand the rates and effects of more extensive repetitive head trauma (symptomatic and asymptomatic) in patients with FTD.

Primary progressive aphasia semantic variant (PPA-SV) is an atypical dementia subtype on the frontotemporal dementia (FTD) spectrum. PPA-SV is clinically defined by naming and semantic deficits, with progressive language decline that generalizes to other domains over time. Typically, it presents as an early-onset dementia with TDP-43 pathology, but 33-46% of PPA-SV cases display initial onset after age 65 with potentially different clinical features. Limbic Predominant Age-Related TDP-43 Encephalopathy (LATE), a more recently discovered neurodegenerative entity, is defined by an older age of onset, hippocampal sclerosis/atrophy, and TDP-43 pathology with a gradually progressive amnestic profile that expands to other cognitive deficits over time. The authors present a case report with overlapping features and suspected TDP-43 neuropathology ante-mortem for two reasons: first, to highlight the need for clinical criteria to formally diagnose LATE, and second, to address a gap in the literature on the possible clinical differences of late-onset PPA-SV.

The authors present a case of a 78-year-old Indian bilingual man (English dominant) with 18 years of education, noncontributory medical history, and gradually progressive cognitive complaints reported over the past few years who was seen for outpatient neuropsychological evaluation. Prior workup was notable for negative amyloid PET scan, negative p-tau 217 blood test, and abnormal brain MRI revealing marked bilateral hippocampal atrophy with ex vacuo ventriculomegaly and minimal cerebrovascular disease. He scored 23/30 on prior MMSE, was diagnosed with amnestic MCI, prescribed Namenda and Exelon, and complained of minor memory and word-finding difficulties with reportedly intact IADLs and no signs of NPH.

Neuropsychological testing revealed a profound dysnomia (RBANS Naming raw score = 1/10), and he provided 0 words on two semantic fluency tasks but 15 words on letter fluency. Receptive vocabulary score was also impaired (PPVT-4, <1st %). Memory performance also demonstrated rapid forgetting of information (RBANS List Recall raw = 0/10, Story Recall raw = 0/12) with no benefit to recognition cues (RBANS List Recognition raw = 12/20), but slightly better visual memory recall, albeit still impaired (RBANS Figure Recall raw = 4/20). Grooved pegboard scores were significantly worse with right-hand than left-hand. Irregular word reading (NAART = 16th %ile) was significantly below expectations and thought to reflect more of a surface dyslexia rather than a cultural confounder given that he has lived in the US for over 50 years and his occupational and educational history was completed in English.

Results support the clinical utility of neuropsychological evaluation in the differential diagnosis to support a predominant clinical syndrome of PPA-SV despite overlapping features with LATE and suspected TDP-43 pathology. This case report highlights the diagnostic issue with the lack of literature describing the typical clinical progression or suggested diagnostic criteria of LATE. These findings also indicate that late-onset PPA-SV may include greater memory deficits earlier in the course, but this may also be a clinical masquerade that is more reflective of the extent of language deficits. Further research on late-onset manifestations of PPA-SV and LATE consensus clinical guidelines is advised.

Depressive symptomatology has long been shown to be associated with the onset of dementia, though the exact form and directionality of this association remains unclear. While much research has gone into confirming this link, there has been little investigation into the effects of depression on dementia progression after diagnosis. The aim of this study is to investigate the relationship between depressive symptomatology and cognitive and behavioural decline over the following year.

In a Rural and Remote Memory Clinic, 375 patients consecutively diagnosed with mild cognitive impairment (MCI), Alzheimer’s Disease (AD), or non-AD dementia completed the Center for Epidemiological Studies Depression Scale (CES-D) at first visit and one-year follow-up to assess depressive symptomatology. The same cohort were evaluated for cognitive and behavioural decline through the completion of five clinical tests performed at the first visit and at one-year follow-up. Cognitive decline was assessed using the Mini Mental Status Exam (MMSE) and the Clinical Dementia Rating Scale (CDR). Neuropsychiatric symptoms were assessed using two subsets of data from the Neuropsychiatric Inventory (NPI severity and distress), both of which are completed by the patients’ caregivers. Functional decline was assessed using the Functional Activities Questionnaire (FAQ). In both cognitive and functional decline, data were analyzed with linear regression analysis in the population subgroups of All Type Dementia (ATD, which includes MCI for this study) (N=375), Alzheimer’s type dementia (N=187), and Mild Cognitive Impairment (N=74).

In this study, we observed no correlation between CES-D scores at baseline and cognitive or functional decline over one year. However, we observed a significant positive correlation between changes in CES-D scores and NPI-severity scores over one year in patients with ATD (likely the most reliable observation from this study due to larger statistical power) and in the MCI subgroup, but not in the AD subgroup. This relationship may be attributable to a relationship between depression and neuropsychiatric symptoms in general, or to the fact that a person with dementia who exhibits more depressive symptomatology appears more impaired and causes greater distress in their caregivers, despite stability in the objective measures of their cognitive and functional status. This finding may indicate that intervention for depression is needed to alleviated caregiver burden when managing dementia patients.

Increasingly severe depressive symptomatology may exacerbate neuropsychiatric symptomatology but did not correlate with cognitive and functional decline in patients with dementia. More studies are needed to help delineate the relationship between depression and dementia progression.

The relationship between frontotemporal dementias (FTDs) and amyotrophic lateral sclerosis (ALS) is well established and is believed to be more pronounced in those with bulbar onset ALS (B-ALS). This study compared cognitive and behavioral symptoms among persons with B-ALS to those of individuals with nonbulbar phenotypes (NB-ALS).

Outpatient clinic data collected during an initial neuropsychology consultation at an ALS interdisciplinary clinic in an academic medical center was retroactively analyzed. All individuals were diagnosed with ALS by neurologists specializing in movement and neuromuscular disorders based on results of neurological/motor examination, electromyographies, and (when available) genotypic data. Total scores on the short form of the Montreal Cognitive Assessment (MoCA-SF) and scores on the ALS Cognitive Behavioral Screen (ALS-CBS) and ALS CBS Caregiver questionnaire were of focus. 22 B-ALS and 44 NB-ALS individuals were compared on said measures using univariate analyses while controlling for ALS symptoms duration.

B-ALS individuals scored significantly lower on the MoCA-SF (F(2)=3.15, p=0.05, n2=0.13) and the tracking subscale of the ALS-CBS (F(2)=3.50, p=0.04, n2=0.17). The groups were not significantly different on other ALS-CBS measures, including caregiver-rated behavior questionnaire.

Consistent with previous research, this study found lower total scores on a brief screener of global cognition and tasks of tracking requiring cognitive control in those with B-ALS relative to NB-ALS individuals. Interestingly, despite behavioral variant being the most prevalent FTD phenotype, the groups did not differ significantly in terms of caregiver-rated behavioral changes. It is hypothesized that the absence of these differences could reflect effects of gradual loss of speech and functionality that secondarily limit caregivers' abilities to observe behavioral changes concerning for possible behavioral variant FTD. That said this could reflect limitations of the sample and/or study design, and further exploration is therefore needed. Recommendations for future studies of neuropsychological/behavioral variables in B-ALS as well as development of more targeted instruments for use in this population are discussed.