Detailed Neuropsychological Testing Research Articles

Diverging Relationships among Amyloid, Tau, and Brain Atrophy in Early-Onset and Late-Onset Alzheimer's Disease.

Alzheimer's disease (AD) dementia may not be a single disease entity. Early-onset AD (EOAD) and late-onset AD (LOAD) have been united under the same eponym of AD until now, but disentangling the heterogeneity according to the age of sonset has been a major tenet in the field of AD research. Ninety-nine patients with AD (EOAD, n=54; LOAD, n=45) and 66 cognitively normal controls completed both [18F]THK5351 and [18F]flutemetamol (FLUTE) positron emission tomography scans along with structural magnetic resonance imaging and detailed neuropsychological tests. EOAD patients had higher THK retention in the precuneus, parietal, and frontal lobe, while LOAD patients had higher THK retention in the medial temporal lobe. Intravoxel correlation analyses revealed that EOAD presented narrower territory of local FLUTE-THK correlation, while LOAD presented broader territory of correlation extending to overall parieto-occipito-temporal regions. EOAD patients had broader brain areas which showed significant negative correlations between cortical thickness and THK retention, whereas in LOAD, only limited brain areas showed significant correlation with THK retention. In EOAD, most of the cognitive test results were correlated with THK retention. However, a few cognitive test results were correlated with THK retention in LOAD. LOAD seemed to show gradual increase in tau and amyloid, and those two pathologies have association to each other. On the other hand, in EOAD, tau and amyloid may develop more abruptly and independently. These findings suggest LOAD and EOAD may have different courses of pathomechanism.

Transient global amnesia after the right temporal epilepsy surgery: A case report.

Transient global amnesia (TGA) is characterized by sudden and temporary memory impairment, while transient epileptic amnesia (TEA) represents amnestic attacks as the main manifestation of focal epilepsy with presumed temporal origin. We present a 48-year-old patient who experienced transient amnesia 10 weeks after right selective amygdalo-hippocampectomy for right temporal lobe epilepsy. Despite TEA being a plausible explanation for amnesia in patients with temporal lobe epilepsy, no epileptiform discharges were found during the amnestic episode and key features indicative of TGA, including long duration, isolated occurrence, and dense anterograde amnesia of the episode, argued against a diagnosis of TEA in this case. Notably, the patient has remained seizure-free (now 4,5 years) and stopped taking antiseizure medication 32 months after surgery. Although TGA clinical criteria formally exclude patients with recent active epilepsy, neurologists should be aware that TGA can occur after epilepsy surgery in the temporal lobe. Therefore, we consider it of high clinical relevance to establish a careful differential diagnosis between TGA and epileptic amnestic attacks after epilepsy surgery to avoid unnecessary reintroduction or continuation of antiseizure medication. Additionally, this case presents the first comparison of detailed neuropsychological test results before and after a presumed TGA episode, revealing a complete recovery of anterograde memory functions within 1 day. PLAIN LANGUAGE SUMMARY: A 48-year-old patient experienced an episode of transient amnesia 10 weeks after epilepsy surgery. Given the patient's history, an epileptic origin of the episode initially seemed likely. However, tests revealed no seizure activity during the episode and the characteristics matched a condition called transient global amnesia. This case highlights the importance of correctly diagnosing memory impairments after epilepsy surgery to prevent unnecessary treatment.

Validity of Montreal Cognitive Assessment to Detect Cognitive Impairment in Individuals with Type 2 Diabetes.

Guidelines recommend screening older people (> 60-65years) with type 2 diabetes (T2D) for cognitive impairment, as it has implications in the management of diabetes. The Montreal Cognitive Assessment (MoCA) is a sensitive test for the detection of mild cognitive impairment (MCI) in the general population, but its validity in T2D has not been established. We administered MoCA to patients with T2D (age ≥ 60years) and controls (no T2D), along with a culturally validated neuropsychological battery and functional activity questionnaire. MCI was defined as performance in one or more cognitive domains ≥ 1.0 SD below the control group (on two tests representing a cognitive domain), with preserved functional activities. The discriminant validity of MoCA for the diagnosis of MCI at different cut-offs was ascertained. We enrolled 267 patients with T2D and 120 controls; 39% of the participants with T2D met the diagnostic criteria for MCI on detailed neuropsychological testing. At the recommended cut-off on MoCA (< 26), the sensitivity (94.2%) was high, but the specificity was quite low (29.5%). The cut-off score of < 23 showed an optimal trade-off between sensitivity (69.2%), specificity (71.8%), and diagnostic accuracy (70.8%). The cut-off of < 21 exhibited the highest diagnostic accuracy (74.9%) with an excellent specificity (91.4%), a good positive and negative predictive value (78.5% and 73.7%, respectively). The recommended screening cut-off point on MoCA of < 26 has a suboptimal specificity and may increase the referral burden in memory clinics. A lower cut-off of < 21 on MoCA maximizes the diagnostic accuracy. Interactive Visual Abstract available for this article.

Different effect of hypo- and hypermetabolism on cognition in dementia with Lewy bodies: are they coupled or independent?

Patients with dementia with Lewy bodies (DLB) show widespread brain metabolic changes. This study investigated whether brain hypo- and hypermetabolism in DLB have differential effects on cognition. We enrolled 55 patients with DLB (15 prodromal DLB [MCI-LB] and 40 probable DLB) and 13 healthy controls who underwent 18F-fluorodeoxyglucose positron emission tomography and detailed neuropsychological tests. Metabolic indices reflecting associated changes in regional cerebral glucose metabolism were calculated as follows: index(-) for hypometabolism [DLB-hypo] and index(+) for hypermetabolism [DLB-hyper]. The effects of DLB-hypo or DLB-hyper on cognitive function were assessed using a multivariate linear regression model. Additionally, a linear mixed model was used to investigate the association between each index and the longitudinal cognitive decline. There was no correlation between DLB-hypo and DLB-hyper in the disease group. The multivariate linear regression model showed that DLB-hypo was associated with language, visuospatial, visual memory, and frontal/executive functions; whereas DLB-hyper was responsible for attention and verbal memory. There was significant interaction between DLB-hypo and DLB-hyper for verbal and visual memory, which was substantially affected by DLB-hyper in relatively preserved DLB-hypo status. A linear mixed model showed that DLB-hypo was associated with longitudinal cognitive outcomes, regardless of cognitive status, and DLB-hyper contributed to cognitive decline only in the MCI-LB group. The present study suggests that DLB-hypo and DLB-hyper may be independent of each other and differentially affect the baseline and longitudinal cognitive function in patients with DLB.

Decoding the clinical effects of low-grade glioma-induced cortical excitability.

Patients with low-grade glioma (LGG) in eloquent regions often present with seizures, and findings on detailed neuropsychological testing are often abnormal. This study evaluated the association between cortical excitability, seizures, and cognitive function in patients with LGG. LGG patients who underwent transcranial magnetic stimulation (TMS) from January 2021 to December 2022 were studied. Cortical excitability was measured using the resting motor thresholds (RMTs) of the upper and lower extremities. Early postoperative seizures served as the seizure endpoint. Neuropsychological assessment was completed prior to surgery contemporaneous with the TMS studies. A total of 31 patients were analyzed for seizure outcome. Median (interquartile range [IQR]) upper-extremity RMT was 39% (34%-46%) of maximum stimulator output, and the median (IQR) lower-extremity RMT was 69% (51%-79%). Lower-extremity RMT was higher in patients with early postoperative seizures, especially in those with motor region tumors (p = 0.02); however, RMT was not associated with seizures at presentation or long-term seizure control. A total of 26 patients completed neuropsychological assessment. There were significant negative correlations between upper-extremity RMT and psychomotor processing speed (Wechsler Adult Intelligence Scale-Fourth Edition [WAIS-IV] Processing Speed Index r = -0.42, p = 0.031; WAIS-IV Coding r = -0.41, p = 0.036; WAIS-IV Symbol Search r = -0.39, p = 0.048), executive function (Trail Making Test Part B r = -0.41, p = 0.036), and hand dexterity (Grooved Pegboard Test r = -0.50, p = 0.047). RMT was positively correlated with early postoperative seizure risk and negatively correlated with psychomotor processing speed, executive function, and hand dexterity. These findings support the theory of local and regional resting oscillatory network dysfunction from a glioma-brain network.

Choroid Plexus Volume, Amyloid Burden, and Cognition in the Alzheimer's Disease Continuum.

As a part of the glymphatic system, the choroid plexus (CP) is involved in the clearance of harmful metabolites from the brain. We investigated the association between CP volume (CPV), amyloid-β (Aβ) burden, and cognition in patients on the Alzheimer's disease (AD) continuum. We retrospectively reviewed the records of 203 patients on the AD continuum and 82 healthy controls who underwent brain magnetic resonance imaging and 18F-florbetaben positron emission tomography. Automatic segmentation was performed, and the CPV was calculated. Cognitive function was assessed using detailed neuropsychological tests, and patients on the AD continuum were categorized into the non-dementia and dementia groups. The relationships between CPV, Aβ burden, and cognitive function were assessed using multivariate linear regression and linear mixed model. CPV was greater in the AD group than in the healthy control group (1.50 vs. 1.30, P < 0.001), but was comparable between the AD non-dementia and dementia groups (1.50 vs. 1.48, P = 0.585). After adjusting for age and sex, a larger CPV was significantly associated with greater global Aβ deposition (β = 0.20, P = 0.002). Larger CPV was also associated with worse general cognitive function assessed using the sum of boxes of the clinical dementia rating scale (β = 0.85, P = 0.034) and lower composite scores for memory (β = -0.68, P = 0.002) and frontal/executive function domains (β = -0.65, P < 0.001). In addition, a larger CPV was associated with a more rapid decline in Mini-Mental State Examination scores in the AD dementia group (β = -0.58, P = 0.004). The present study demonstrated that CP enlargement was associated with increased Aβ deposition and impaired memory and frontal/executive function in patients on the AD continuum.

The use of inhaled nitric oxide (Tianox device) in patients with moderate cognitive impairment

Mild cognitive impairment (MCI) is an intermediate stage between normal cognitive function (CF) and dementia. In the general population of elderly, it is diagnosed in 10–15% of cases; in patients attending outpatient appointments, the frequency of diagnosis is 70%. In our country, there is positive experience with the inhalation of nitric oxide, using a device that synthesizes it from the air, for pulmonary and cardiovascular diseases.Objective: to investigate the use of inhaled nitric oxide (Tianox device) in patients with MCI due to cerebrovascular (CVD) and neurodegenerative diseases (NDD) of the brain.Material and methods. We observed 36 patients (8 men, 28 women, mean age 66±8.9 years, from 50 to 76 years) with MCI that developed on the background of CVD and NDD. In addition to stroke prevention therapy, the patients with MCI received daily inhalation of a nitric oxideenriched air mixture via a Tianox device for 30 minutes. The patients had from 7 to 10 inhalation sessions (the first, experimental – 20 minutes, the following sessions – 30 minutes). Detailed neuropsychological tests were performed at baseline and 3 months after the end of treatment.Results. The therapy was well tolerated and no adverse events occurred. After 3 months, the average score on the Montreal Cognitive Assessment increased from 23.7±3.5 to 25.6±3.9 points (p&lt;0.001), the ability to memorize 12 words – from 7.5±1.8 to 8.7±2.1 words (p&lt;0.05), categorical associations – from 14.8±5.0 to 16.9±4.6 words (p&lt;0.05), the number of words found in the Munsterberg test – from 14.9±5.8 to 18.1±5.8 (p&lt;0.001).The emotional state of the patients improved, the signs of depression decreased according to the Beck Depression Inventory from 13.65±8.5 to 11.4±6.7 points (p&lt;0.05), on the Hospital Anxiety and Depression Scale – from 8.6± 5.0 to 7.3±4.1 points (p&lt;0.05); anxiety decreased on the Hospital Anxiety and Depression Scale – from 7.0±5.0 to 5.4±4.5 points (p&lt;0.05), Insomnia Severity Index – from 11.1±7.9 to 7.8±6.3 points (p&lt;0.05).Conclusion. Good tolerability and a positive effect of inhaled nitric oxide on CF and emotional state of patients with MCI against the background of CVD and NDD were found.

The association between menopause and dementia risk

AbstractBackgroundWomen have a higher prevalence of Alzheimer’s disease compared to men. Studies are conflicting as to whether an earlier age of menopause or hysterectomy prior to natural menopause, are associated with an increased risk of cognitive impairment. The goal of this study was to determine whether age of menopause and hysterectomy are associated with incident dementia in a group of older, community‐dwelling women.MethodFemale participants from three ongoing Rush cohorts, the Rush Memory and Aging Project, the Religious Orders Study, and the Minority Aging Research Study were included (total n = 3122, mean age = 77 years at baseline, SD = 7.8). Annual clinical assessments allowed for dementia status categorization, based on detailed neuropsychological testing and clinical judgment, using the NINDS‐ADRDA criteria. Age at menopause and hysterectomy status was based on self‐report at baseline. Data on ovarian preservation or removal at time of surgery was not available. Age of menopause was categorized into tertiles (&lt;45, 45‐50, &gt;50). Risk of dementia, with age at dementia diagnosis as the outcome, was evaluated using Cox proportional regression models adjusting for race, early‐life socioeconomic status, education, diabetes, and smoking status.ResultAt the time of these analyses, women were followed for an average of 8.3 years (SD = 5.6). Women in the earliest tertile of menopause age were less likely to be white, more likely to report having diabetes, and have longer hormone therapy use (p&lt;0.01). In fully adjusted models, women with menopause at age 45‐50 (HR 0.80, 95% CI 0.67‐0.96) and age &gt;50 (HR 0.74, 95% CI 0.62‐0.90) had a lower risk of dementia compared to women with menopause at age &lt;45. Hysterectomy prior to natural menopause was not associated with an elevated risk of dementia (HR = 1.01, 95% CI 0.87‐1.19).ConclusionIn a group of older women, earlier age at menopause but not hysterectomy was associated with an elevated risk of dementia. Future research will determine whether these associations differ by race or ethnicity and the factors that may contribute to such differences.Funding: P30‐AG072975, R01‐AG17917, R01‐AG22081

In vivo Braak staing using 18F‐MK‐6240 PET in Alzheimer’s disease

AbstractBackgroundThis study aimed to identify the distribution of [18F]MK‐6240 PET retention and classified according to Braak staging in Alzheimer’s disease (AD). We also evaluated the relationship between [18F]MK‐6240 PET retention and cognitive functions and neurodegeneration.MethodWe enrolled 194 participants including 70 CU (cognitively unimpaired elderly participants older than 60 years old), 56 MCI, 60 probable AD, and 8 patients who had dementia other than AD (subcortical vascular dementia (n = 3), semantic variant primary progressive aphasia (n = 2), frontotemporal dementia (n = 2), corticobasal syndrome (n = 1)). All participants underwent 3T MRI, [18F]MK‐6240, and [18F]Flutemetamol (FLUTE) PET scans, APOE genotyping, and detailed neuropsychological tests. Braak staging was defined as the stages where regional SUVR of ROIs composing each Braak stage &gt; = 1.3. We assessed the Braak staging in the subjects. Correlation analyses between global retention of MK‐6240 PET and neuropsychological test results or neurodegeneration were performed using linear regression.ResultThe proportion of amyloid positivity was 11.4% in CU, 45.5% in MCI, and 83.3% in probable AD. Among probable AD (n = 60), 12 patients were classified to other dementia after amyloid PET and tau PET confirmation. Main Braak stage was Braak 0 in CU, Braak III/IV in amyloid (+) MCI, Braak V/VI in AD dementia. In CU an patents with AD spectrum, global retention of MK‐6240 PET was significantly correlated with MMSE, CDR SOB, language, visuospatial function, memory and frontal/executive functions. In addition, global retention of MK‐6240 PET was correlated with the MRI markers for neurodegeneration, that is, mean cortical thickness and hippocampal volumes.Conclusion [ 18F]MK‐6240 PET successfully identified the Braak staging and associated with amyloid pathology and clinical phenotype in patients with AD. MK‐6240 PET also correlated with cognitive functions and neurodegeneration. MK6240 is a promising tau PET tracer with the potential to be sensitive surrogate markers of AD.

Importance of individual dietary factors for cognitive performance in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, FINGER

AbstractBackgroundFinnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a randomized trial that showed beneficial effect on cognition with a 2‐year multidomain lifestyle intervention. One of the four multidomain intervention components was diet and we have earlier shown that overall adherence to the FINGER dietary intervention goals was associated with better cognition. Here our aim is to investigate how the individual components of the dietary adherence score are associated with cognitive performance during the 2‐year period.MethodThe FINGER cohort included 1259 individuals at risk of dementia aged 60‐77 years at baseline, randomized into the multidomain intervention (n = 631) or the control group (n = 628). They underwent extensive data collection annually (total of 3 assessments), including detailed neuropsychological test battery (NTB) and a 3‐day food record. Adherence to dietary intervention was evaluated on 9 items based on dietary recommendations: intake of saturated fat, polyunsaturated fat, sucrose, fiber, protein, alcohol, vegetables, fruits, and fish. Data analyses were completed with mixed‐effects regression.ResultThe goal for low alcohol intake was inversely associated with cognition at baseline, but no other dietary items showed cross‐sectional associations. Reaching the goal for saturated fat, fiber, vegetables, fruits, and fish predicted better cognitive change at two years (p &lt;0.05 for goal*time each). Results were similar when continuous variables rather than dichotomized goals were investigated. Intake of polyunsaturated fats additionally predicted better cognitive change and vegetable intake showed positive cross‐sectional association with cognition. There were no significant interactions with the study group.ConclusionSix out of nine FINGER dietary goals predicted a favorable cognitive change over time, indicating that a dietary pattern adherence with general dietary recommendations is beneficial for brain health. However, alcohol intake goal, i.e. lower alcohol intake, was associated with worse cognition; and cut‐offs for polyunsaturated fats based on the recommendations appeared suboptimal. The FINGER dietary adherence score should be compared with food‐based dietary patterns like Mediterranean Diet to investigate if nutrient intakes should be better taken into account when analyzing diet in relation to cognitive performance.

Relationship between metabolic disease and Alzheimer’s disease

AbstractBackgroundDiabetes is an enormous and growing global public health problem, associated with poor health outcomes including dementia. Mechanisms underlying the relationship of diabetes to dementia are less well understood.MethodsWe leveraged several large, ongoing community‐based cohorts of older women and men with and without diabetes, taking part in longitudinal, clinical‐pathologic studies of aging at the Rush Alzheimer’s Disease Center. Participants undergo annual clinical evaluations including detailed neuropsychological testing, and brain autopsy at time of death. We examined the relation of diabetes and related clinical variables (e.g., medications, body mass index [BMI], hypertension), and blood and brain biomarkers of insulin resistance and other measures (e.g., epigenetics), to brain outcomes. Level and change in global cognition and five cognitive domains were based on neuropsychological tests, and dementia status was classified. Postmortem human brain specimens of deceased persons were systematically evaluated for neuropathology, including neurodegenerative (e.g., Alzheimer’s disease [AD]) and cerebrovascular disease (e.g., infarcts).ResultsDiabetes, present in 15‐20% of our cohorts, is associated a two‐fold increased risk of dementia and relates to cognitive decline (particularly in some cognitive domains more than others), and these observations are found in both Black and White participants. Some diabetes‐related clinical variables (e.g., BMI) are associated with faster cognitive decline, while others such as medications (metformin) are associated with slower cognitive decline. Regarding human postmortem neuropathologic outcomes, diabetes is associated with cerebrovascular pathologies, and small subcortical infarcts in particular. But, while we have not found clear associations of diabetes with neurodegenerative pathologies such as AD, some brain molecular markers in the insulin signaling pathway (AKT1) are associated with AD (including amyloid‐beta and tau tangles) and cognition (memory). Recently, using blood and brain specimens, we show that genome‐wide 5‐hydroxymethylcytosine profiling uncovers epigenetic features and biologic pathways related to nucleotide sugar metabolism linking diabetes to diabetes‐associated AD.ConclusionDiabetes is a potentially‐modifiable risk factor for dementia and cognitive decline. Clinical, neuropathologic, and epigenetic factors are at play in the underlying mechanisms. A better understanding of mechanisms will inform future research and offer opportunities for precision medicine and dementia prevention (supported by NIH: R01NS084965, RF1AG059621, RF1AG074549, R01AG022018, P30AG10161, P30AG072975, R01AG15819, R01AG17917).

Utility of Mini‐Mental State Examination items to detect objective memory impairment in mild cognitive impairment

AbstractBackgroundAlzheimer’s disease (AD) is the main cause of cognitive impairment in late‐life, and the typical early presentation of AD in older adults is amnestic cognitive impairment. Mini‐Mental State Examination (MMSE) is widely used in screening cognitive impairment in elderly. The aim of this study was to examine which MMSE items would be more associated with the verbal memory impairment in individuals with mild cognitive impairment (MCI).Method249 MCI subjects (mean age: 73.67 ± 6.79 years) were included in this study. The participants underwent clinical assessments and completed detailed neuropsychological tests. The participants were divided into two groups according to Seoul Verbal Learning Test Delayed Recall (SVLT DR) scores: normal verbal memory performance (SVLT DR &gt; = ‐1.5 SD) vs low verbal memory performance (SVLT DR &lt; ‐1.5 SD) groups. Group comparisons between normal and low verbal memory performance were performed. In addition, associations between verbal memory performance and MMSE items were analysed.ResultLow verbal memory performance group (n = 91) had more males and a tendency to be older and more educated than normal verbal memory performance group (n = 158). For MMSE items, low verbal memory performance group had lower MMSE time orientation and lower MMSE recall subscores, and a tendency of higher MMSE copy score than normal verbal memory performance group. Multivariable analyses showed that male sex, MMSE time orientation and MMSE recall scores were associated with lower verbal memory performance.ConclusionIn MCI individuals, male sex, and MMSE time orientation and recall subscores among demographics and MMSE items were associated with low verbral memory performance. These results suggest that more consideration for MMSE sub‐items would be helpful for the clinical evaluation of individuals with MCI at first step.

Associations of Orthostatic Hypotension and Orthostatic Intolerance with Domain-Specific Cognitive Decline in Patients with Early Parkinson Disease: An 8-Year Follow-up

ObjectiveAlthough orthostatic hypotension (OH) and orthostatic intolerance (OI) are prevalent in patients with Parkinson disease (PD), it remains unclear how these conditions primarily affect the trajectory of decline in specific cognitive domains. This study aimed to explore the effects of OH and OI on longitudinal domain-specific cognitive changes in patients with PD. DesignAn 8-year follow-up of the Parkinson Progression Markers Initiative cohort study. Setting and ParticipantsA total of 403 patients with early, untreated PD and 195 matched healthy controls were included. They were classified into OH, OI, and normal groups. OH was defined according to the international consensus, and OI was defined as the presence of orthostatic symptoms without meeting the criteria for OH. MethodsThe patients underwent detailed neuropsychological testing annually for up to 8 years of follow-up. Linear mixed effects models were used to investigate the associations between OH, OI, and longitudinal cognitive changes. ResultsThe prevalence of both OH and OI in patients with PD was significantly higher than that in controls (13.4% vs 7.2%, P = .002, for OH, and 29.3% vs 14.4%, P < .001, for OI). The OH group in patients with PD showed a faster decline in Letter-Number Sequencing (LNS) (β = −0.11, 95% CI −0.20 to −0.02, t = −2.44, P = .015) and Semantic Fluency Test (SFT) (β = −0.44, 95% CI –0.81 to −0.08, t = −2.42, P = .016) scores than the normal group. Similarly, the OI group showed a steeper decline in LNS (β = −0.08, 95% CI –0.14 to −0.01, t = −2.20, P = .028) and SFT (β = −0.36, 95% CI –0.63 to −0.08, t = −2.55, P = .011) scores compared to the normal group. There were no significant longitudinal changes in the other neuropsychological test scores between the groups. Conclusions and ImplicationsBoth OH and OI may be associated with a faster decline in executive function among cognitive domains of patients with PD. These findings may highlight the potential importance of orthostatic blood pressure control in PD patients with OH and even those with orthostatic symptoms without OH.

A case of severe anterograde amnesia in the era of smartphone technology

ABSTRACT A.V. is a young herpes simplex encephalitis (HSE) survivor who suffered extensive bilateral damage to the medial temporal lobe (MTL) leading to a severe and pervasive form of anterograde amnesia. Structural Magnetic Resonance Imaging (MRI) revealed lesions that encompass the hippocampus and amygdala in both hemispheres and that extend more laterally in the right temporal lobe. At the same time, detailed neuropsychological testing showed that the disparity between A.V.’s preserved intellectual functioning (Full Scale IQ: 115) and severe memory deficit (Delayed Memory Index: 42) is one of the largest on record. Despite this deficit, A.V. has regained a higher level of functioning and autonomy compared to previously documented amnesic cases with major bilateral MTL lesions. As a millennial, one advantage which A.V. has over prior amnesic cases is fluency with digital technology – particularly the smartphone. The analysis of his phone and specific app usage showed a pattern that is consistent with the strategy to offload cognitive tasks that would normally be supported by the MTL. A.V.’s behavior is significant in terms of rehabilitation and may have broader implications at the societal level and for public health given the ubiquity of smartphone technology and its potential to become integrated with neural mnemonic functions.

23 Cognitive Reserve Moderates Cognitive Functioning in Late-Life Depression

Objective:The concept of cognitive reserve (CR) explains why individuals with higher education, intelligence, or occupational attainment exhibit less severe cognitive changes in the presence of age-related or neurodegenerative pathology. CR may be a useful construct in understanding the cognitive performance of patients with late life depression (LLD), a cohort who are twice as likely to later receive a clinical diagnosis of dementia. It follows that depressed older adults with low CR may be at greater risk of cognitive decline compared to non-depressed older adults matched for CR. However, the literature on CR and LLD is limited to cross-sectional studies with mixed findings as to whether proxies of CR moderate cognitive outcomes in LLD. For example, both higher and lower education levels in LLD are associated with greater cognitive impairment in LLD compared to similarly educated non-depressed older adults. Longitudinal studies may help disentangle the association between CR and cognitive outcomes in LLD. The current study investigated the interaction between proxies of CR (e.g., education) and depression status on cognitive functioning over three years. We hypothesized that depressed older adults with low CR would demonstrate greater cognitive impairment and decline compared to depressed elders with high CR and non-depressed older adults with comparable CR.Participants and Methods:Older adults with LLD and non-depressed older adults age 59+ participated. All participants were free of dementia at baseline. We divided both patients and non-depressed participants into low (&lt;16) and high (&gt;=16) education groups based upon the median years of education (16) of the entire sample. All participants underwent detailed neuropsychological testing. Composite measures of episodic memory (CERAD Wordlist and recall, LM I and LM II, BVRT), processing speed-executive functioning (SDMT and Trail Making Part B), working memory (forward, reverse, ascending Digit Span), and verbal fluency (Animal Naming and COWA) were calculated based on the non-depressed older adults.Results:The baseline sample included 210 non-depressed older adults and 465 older adults with major depression (LLD). 150 non-depressed older adults and 235 LLD patients provided three-year follow-up data. Separate ANOVAs revealed a statistically significant interaction between education and depression status at baseline on the composite score of executive functioning F (1, 668) = 8.74, p &lt;.003. Consistent with our hypothesis, LLD with low education performed significantly worse compared to non-depressed with low education (z-score difference -1.35) and this effect was significantly greater than the difference between LLD patients and non-depressed with high education (z-score difference -0.36). No other interactions were found at baseline. Longitudinal analyses also revealed significant interactions between education and depression on memory over time, although sensitivity analyses did not suggest findings consistent with our hypothesis.Conclusions:Cognitive reserve contribute to group differences between LLD and non-depressed older adults in cognitive performance but may not alter cognitive trajectories over time. Future studies should further explore structural and functional brain changes associated with CR in LLD.

A prospective cohort study of familial versus sporadic essential tremor cases: Do clinical features evolve differently across time?

BackgroundAlthough essential tremor (ET) is often divided into familial and sporadic cases, few data compare the evolution of clinical features in these groups over time. Leveraging data from a prospective, longitudinal study, we present analyses of the evolution of a broad range of cognitive, motor (i.e., tremor, tandem gait) and other features (e.g., disability) of ET. MethodsSixty-six familial and 23 sporadic ET cases completed in-home evaluations at baseline and 18, 36, and 54-month follow-ups. Assessments included detailed neuropsychological testing and videotaped neurological examinations. Analyses compared the longitudinal course of 16 clinical features in familial and sporadic cases. ResultsBaseline mean age was 75.2 ± 8.8 years and mean observation period was 4.7 ± 0.3 years. Tremor onset age was lower and childhood onset more common in familial than sporadic cases (p's = 0.02). Longitudinal analyses revealed no significant differences between clinical features displayed by familial and sporadic cases, or differences between the patterns of change in clinical features observed in these groups across time. Sporadic cases' daily activity skills declined significantly, whereas familial cases' did not, p's = 0.04 and 0.34, respectively; however, this finding was non-significant when controlling for false discovery rate. Several additional non-significant trends were noted. ConclusionFamilial and sporadic ET cases differed in onset age, and in the prevalence of childhood tremor onset. Although a number of interesting trends were observed, no significant differences in the evolution of clinical features over time in patients with and without a family history of ET were revealed.

Association of Sleep Disturbances With Brain Amyloid and Tau Burden, Cortical Atrophy, and Cognitive Dysfunction Across the AD Continuum.

Patients with Alzheimer disease (AD) frequently suffer from various sleep disturbances. However, how sleep disturbance is associated with AD and its progression remains poorly investigated. We investigated the association of total sleep time with brain amyloid and tau burden, cortical atrophy, cognitive dysfunction, and their longitudinal changes in the AD spectrum. In this retrospective cohort study, we enrolled participants on the AD spectrum who were positive on 18F-florbetaben (FBB) PET. All participants underwent the Pittsburgh Sleep Quality Index, brain MRI, FBB PET, 18F-flortaucipir (FTP) PET, and detailed neuropsychological testing. In addition, a subset of participants completed follow-up assessments. We analyzed the association of total sleep time with the baseline and longitudinal FBB-standardized uptake value ratio (SUVR), FTP-SUVR, cortical thickness, and cognitive domain composite scores. We examined 138 participants on the AD spectrum (15 with preclinical AD, 62 with prodromal AD, and 61 with AD dementia; mean age 73.4 ± 8.0 years; female 58.7%). Total sleep time was longer in the AD dementia group (7.4 ± 1.6 hours) compared with the preclinical (6.5 ± 1.4 hours; p = 0.026) and prodromal groups (6.6 ± 1.4 hours; p = 0.001), whereas other sleep parameters did not differ between groups. Longer total sleep time was not associated with amyloid accumulation but rather with tau accumulation, especially in the amygdala, hippocampus, basal forebrain, insular, cingulate, occipital, inferior temporal cortices, and precuneus. Longer total sleep time predicted faster tau accumulation in Braak regions V-VI (β = 0.016, p = 0.007) and disease progression to mild cognitive impairment or dementia (hazard ratio = 1.554, p = 0.024). Longer total sleep time was also associated with memory deficit (β = -0.19, p = 0.008). Prolonged total sleep time was associated with tau accumulation in sleep-related cortical and subcortical areas as well as memory dysfunction. It also predicted faster disease progression with tau accumulation. Our study highlights the clinical importance of assessing total sleep time as a marker for disease severity and prognosis in the AD spectrum.

A - 40 Assessment of Dementia with Lewy Bodies in a Patient with both Characteristic and Atypical Features.

Dementia with Lewy Bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer disease (ad). Its heterogeneous presentation and overlapping features with other dementias result in frequent misdiagnosis, which can delay optimal management. The present case illustrates complex symptomology, comprehensive assessment, and diagnostic challenges in a patient with DLB. A 64-year-old female presented to an academic medical center neurology clinic with rapid cognitive deterioration over the past 1.5years accompanied by visual disturbances, psychiatric and behavioral changes, and mild motor symptoms. Initial differential included Creutzfeldt-Jakob disease, atypical parkinsonism, frontotemporal lobar degeneration (FTLD), encephalopathy, and ad. Work-up in included neuropsychological, neuroimaging, cerebral spinal fluid (CSF), electroencephalogram (EEG), and skin biopsy assessments. Neuropsychological interview revealed fluctuating attention/alertness, visual hallucinations, hyposmia, paranoid and repetitive behaviors, and subtle evidence for dream enactment. Her cognitive profile showed global impairment with pronounced visuospatial and executive deficits. Recognition memory, verbal reasoning, and naming were relatively well-preserved. Magnetic resonance imaging showed mild atrophy; fluorodeoxyglucose positron emission tomography (PET) showed hypometabolism in frontal and temporal regions whereas uptake was highest in the occipital lobes and basal ganglia; skin biopsy was positive for synucleinopathy; CSF and EEG were broadly unrevealing. The preponderance of data was consistent with diagnostic criteria for probable DLB. Skin biopsy increased diagnostic confidence. Atypical features included relatively rapid cognitive decline, minimal parkinsonism, and PET imaging suggesting FTLD. The present case highlights the utility of a multidisciplinary approach (e.g., neurological exam, detailed symptom screening, neuropsychological testing, and advanced laboratory assessments) in a complex case of DLB.

Utility of the NIH Toolbox Cognition Battery in middle to older aged adults with longstanding type 1 diabetes: The DCCT/EDIC study

Objective: Adults with type 1 diabetes (T1D) face an increased risk for cognitive decline and dementia. Diabetes-related and vascular risk factors have been linked to cognitive decline using detailed neuropsychological testing; however, it is unclear if cognitive screening batteries can detect cognitive changes associated with aging in T1D. Method: 1,049 participants with T1D (median age 59 years; range 43–74) from the Diabetes Control and Complications Trial (DCCT), and the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, completed the NIH Toolbox Cognition Battery (NIHTB-C) and Montreal Cognitive Assessment (MoCA). Neuropsychological assessments, depression, glycated hemoglobin levels (HbA1c), severe hypoglycemia, T1D complications, and vascular risk factors were assessed repeatedly over 32 years to determine associations with current NIHTB-C performance. Available cognitive data was clinically adjudicated to determine cognitive impairment status. Results: NIHTB-C scores had moderate associations (r = 0.36–0.53) with concurrently administered neuropsychological tests. In multivariate models, prior severe hypoglycemic episodes, depression symptoms, nephropathy, lower BMI, and higher HbA1c and LDL cholesterol were associated with poorer NIHTB-C Fluid Cognition Composite scores. The NIHTB-C adequately detected adjudicated cognitive impairment (Area Under the Curve = 0.86; optimal cut score ≤90). The MoCA performed similarly (Area Under the Curve = 0.83; optimal cut score ≤25). Conclusions: The NIHTB-C is sensitive to the cognitive effects of diabetes-related and vascular risk factors, correlated with neuropsychological testing, and accurately detects adjudicated cognitive impairment. These data support its use as a screening test in middle to older aged adults with T1D to determine if referral for detailed neuropsychological assessment is needed.

Association between choroid plexus volume and cognition in Parkinson disease.

The choroid plexus (CP) clears harmful metabolites from the central nervous system as part of the glymphatic system. We investigated the association of CP volume (CPV) with baseline and longitudinal cognitive decline in patients with Parkinson disease (PD). We retrospectively reviewed the medical records of 240 patients with newly diagnosed PD who had undergone detailed neuropsychological tests and high-resolution T1-weighted structural magnetic resonance imaging during the initial assessment. The CPV of each patient was automatically segmented, and the intracranial volume ratio was used in subsequent analyses. The relationship between CPV and baseline composite scores of each cognitive domain was assessed using multivariate linear regression analyses. A Cox proportional hazards model was used to compare the risk of dementia conversion with CPV. CPV negatively correlated with composite scores of the frontal/executive function domain (β = -0.375, p = 0.002) after adjusting for age, sex, years of education, and parkinsonian symptom duration. The Cox regression model revealed that a larger CPV was associated with a higher risk of dementia conversion (hazard ratio [HR] = 1.509, p = 0.038), which was no longer significant after adjusting for the composite scores of the frontal/executive function domain. A mediation analysis demonstrated that the effect of CPV on the risk of dementia conversion was completely mediated by frontal/executive function (direct effect: HR = 1.203, p = 0.396; indirect effect: HR = 1.400, p = 0.015). Baseline CPV is associated with baseline frontal/executive function, which subsequently influences dementia conversion risk in patients with PD.