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CurrentAetnaPolicy 0788

Alzheimer's Disease: Experimental Treatments

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Defines Aetna's stance that multiple listed therapies for Alzheimer's disease are considered experimental/investigational and not established for this indication; affects providers seeking coverage for these therapies under Aetna plans.

Policy Summary

PayerAetna

PolicyAlzheimer's Disease: Experimental Treatments

Policy CodePolicy 0788

Change TypeNo material change

Effective DateJun 19, 2009

Last ReviewFeb 20, 2024

Next Review DateAug 22, 2024

Key ActionObtain and document enrollment in a recognized clinical trial or approved research protocol when proposing investigational therapies.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

65experimental treatments listed

Multiplecodes listed as not covered

G30.0-G30.9ICD-10 range referenced

Mixed/negativemixed/negative trial findings

1,958verubecestat randomized patients

97%UB-311 antibody response

Coverage Criteria — Experimental / Investigational Treatments for Alzheimer's Disease

Experimental / Investigational (Not Established)

Aetna considers the following treatments for Alzheimer's disease experimental and investigational because their effectiveness for this indication has not been established (not an all-inclusive list).

Listed therapies: Therapies numbered 1–65 in the policy are considered experimental/investigational for Alzheimer's disease

See policy list in chunks 4–6 for specific therapies; items include acupuncture, bapineuzumab, solanezumab, CSF shunting, vagus nerve stimulation, intranasal insulin, BACE inhibitors, and others

Evidence summaries

Evidence summaries and coverage-relevant conclusions

Semagacestat evidence: Randomized data showed no cognitive improvement and worse functional ability; associated with more adverse events including skin cancers and infections.

Supports investigational/not medically necessary stance

Policy Summary

PayerAetna

PolicyAlzheimer's Disease: Experimental Treatments

Policy CodePolicy 0788

Change TypeNo material change

Effective DateJun 19, 2009

Last ReviewFeb 20, 2024

Next Review DateAug 22, 2024

Key ActionObtain and document enrollment in a recognized clinical trial or approved research protocol when proposing investigational therapies.

SourceLink

On This Page

Vagus nerve stimulation (VNS): Small open-label and follow-up studies reported some cognitive responder rates and tolerability, but evidence is limited and further controlled studies are needed.

Insufficient evidence for routine coverage

Intravenous immunoglobulin (IVIG): Pilot studies (n=5) demonstrated CSF/serum Abeta changes and limited cognitive signal; sample sizes too small to draw definitive conclusions.

Investigational pending larger RCTs

Hormone replacement therapy (HRT/ERT): Randomized trials and Cochrane review found no consistent cognitive benefit and some signals of worse performance on global ratings; HRT/ERT is not indicated for cognitive improvement in women with AD.

Not recommended for cognitive treatment

Statins: Systematic reviews and a large RCT (simvastatin, n=406) showed lipid lowering without benefit on ADAS-Cog or other cognitive outcomes.

Insufficient evidence to support use for AD cognition

NSAIDs (naproxen, celecoxib, indomethacin): Randomized trials and meta-analyses did not show cognitive benefit; naproxen showed weak evidence of detrimental effect in one large trial.

Not supported for treatment of AD cognitive decline

Huperzine A: Some small trials and meta-analyses reported short-term cognitive signals, but most studies were low quality and a phase II trial failed its primary endpoint at 200 μg BID.

Insufficient high-quality evidence for routine use

Intranasal insulin: Pilot and randomized studies (including n=104) showed preservation of some memory and function measures and favorable safety in trials; results support larger, longer trials but remain investigational.

Promising but not established

Continuous CSF drainage / low-flow ventriculo-peritoneal shunt: A randomized sham-controlled trial (n=215) was halted for futility; no benefit on primary outcomes and higher-than-expected CNS infections associated with the procedure.

Not supported and associated with safety concerns

Investigational Treatments — evidence summary

Summary of investigational treatments and their trial-level findings

Noninvasive neuromodulation (tDCS, gamma stimulation): tDCS studies and meta-analysis show heterogeneous evidence with some positive effects on memory and general cognition but high study heterogeneity and limited sample sizes; gamma-band stimulation remains preclinical/early clinical.evidence insufficient

See chunks 38–39, 78

Intranasal insulin: Preliminary data indicate memory and functional preservation in some trials and support longer trials; evidence remains limited.evidence insufficient

See chunks 34–36

CSF shunting: Randomized sham-controlled trial halted for futility with no benefit and increased CNS infections; not supported for AD treatment.not effective

See chunk 37

Monoclonal anti-amyloid antibodies (bapineuzumab, solanezumab): Phase II/III trials did not demonstrate consistent clinical benefit; some biomarker effects observed but accompanied by safety signals including ARIA/vasogenic edema; clinical efficacy not established.not established clinically

See chunks 45,47,55–57

Vaccine therapy (UB-311 and others): Active vaccines previously halted for meningoencephalitis; newer vaccines like UB-311 show immunogenicity and tolerability in small trials but require further study.investigational

See chunks 41–42

Stem cell therapies: Preclinical and small-animal data suggest potential benefit but clinical effectiveness is lacking and evidence is insufficient for clinical use.preclinical/insufficient

See chunks 43–44

Etanercept (TNF inhibition): Small randomized and open-label trials show tolerability but no convincing efficacy; infections were more common in treated groups.insufficient evidence

See chunk 51

Light therapy: Studies report mixed findings for sleep and cognition with methodological variability; current evidence is inconclusive.inconclusive

See chunk 54

Other pharmacologic classes (BACE inhibitors, H3 antagonists, PPAR-γ agonists, GLP-1 agonists, TKIs, statins, idalopirdine, raloxifene, resveratrol, edonerpic maleate): Multiple agents across classes have shown biomarker effects or preclinical promise but failed to demonstrate consistent, clinically meaningful cognitive or functional benefits in randomized trials; some trials terminated for futility and some agents had notable adverse events.insufficient/negative trial results

See chunks 56–57, 67, 70–73, 77, 79, 83, 90

Coverage for investigational therapies (conditional)

Covered when ALL of the following are met

Use within clinical trial or approved research protocol: Patient is enrolled in a recognized clinical trial or approved research protocol with appropriate IRB oversight and informed consent; trial protocol and enrollment documentation are submitted for review.

Support: multiple items describe investigational status and recommend study-based use

Documented safety monitoring per protocol: Baseline and follow-up assessments (e.g., cognitive scales such as ADAS-Cog/MMSE, MRI and/or CSF biomarker collection where applicable) and adverse event monitoring are documented according to the trial protocol.

Several trials reported MRI/CSF biomarker collection and safety signals (e.g., ARIA)

Investigational / Not established therapies

Implied coverage stance based on clinical evidence summarized in these background sections

Investigational agents without proven clinical benefit: Agents discussed (e.g., raloxifene, resveratrol, lanabecestat, verubecestat, crenezumab, edonerpic maleate, amytrap, gemfibrozil, gamma stimulation, acupuncture, home-based occupational therapy, non-pharmacologic agitation therapies) are investigational or lack demonstrated clinically meaningful efficacy in trials cited; some trials were terminated for futility or failed primary endpoints.

Multiple randomized trials reported no significant cognitive or functional benefit or were terminated for futility; biomarker changes alone do not establish clinical benefit

Aetna identifies a list of CPT, HCPCS and ICD-10 codes that are not covered when billed for the experimental indications described in this bulletin. Examples include procedural and device codes for CSF shunting and implanted neurostimulators (e.g., 62160, 62180-62258, 61863-61868, L8680-L8695), codes for immune globulin products and apheresis/plasma exchange (e.g., 36514, 36516, J1459, J1561–J1569, 90281–90283), fecal microbiota transplantation and related preparation codes (e.g., 0780T, 44705, G0455, J1440), selected drug injection codes (e.g., J0135, J1438, J1745), and the ICD-10 diagnosis codes for Alzheimer’s disease (G30.0–G30.9).

Providers should expect these listed codes to be treated as associated with experimental/investigational services for Alzheimer’s disease and therefore not covered when used for the interventions named in this policy (see code listings in the CPT/HCPCS/ICD-10 sections).

A randomized, double-blind, placebo-controlled trial of low-flow ventriculo-peritoneal CSF shunting in 215 subjects with probable Alzheimer’s disease was halted for futility after interim analysis; there were no between-group differences on the primary outcomes (Mattis Dementia Rating Scale and Global Deterioration Scale). The procedure was associated with increased adverse events, including 12 CNS infections, some temporally linked to CSF sampling, and the authors concluded there was no benefit to low-flow CSF shunting in mild-to-severe AD.

Systematic reviews and randomized trials of hormone replacement therapy (HRT/ERT) in postmenopausal women with dementia do not show consistent cognitive benefit. A Cochrane review (7 trials, 351 women) reported some measures worse with conjugated equine estrogens and limited, transient findings with low-dose preparations; the authors concluded that HRT/ERT is not indicated for cognitive improvement or maintenance in women with AD.

Based on the randomized sham‑controlled trial evidence, CSF shunting for Alzheimer’s disease is not supported. The RCT showed no cognitive or functional benefit and demonstrated an increased risk of central nervous system infections associated with the surgical procedure and study-related CSF sampling.

Multiple agents that reached randomized controlled testing failed to demonstrate clinically meaningful benefit and therefore are excluded from routine coverage. Examples include anti-amyloid antibodies and small molecules where pivotal trials were neutral (e.g., solanezumab), serotonin 5-HT antagonists (e.g., idalopirdine), histamine H3 receptor antagonists, and selective estrogen receptor modulators (e.g., raloxifene); the aggregated trial data do not support routine medical necessity for these interventions.

In a large, randomized, double-blind, placebo‑controlled 78‑week study of the BACE‑1 inhibitor verubecestat (n=1,958 randomized), the trial was terminated early for futility. There were no significant differences versus placebo on the co‑primary outcomes (ADAS‑cog and ADCS‑ADL) and adverse events (including rash, falls, sleep disturbance, weight loss and suicidal ideation) were more common in the active arms; these results do not support clinical use of verubecestat for mild‑to‑moderate AD.

A phase II randomized study of crenezumab (n=431) did not meet its primary or secondary endpoints. An exploratory post‑hoc signal favoring higher‑dose treatment in a milder subset (MMSE 22–26) was observed, but overall results were insufficient to establish efficacy for routine clinical use and support only further study at higher doses in earlier disease.

Sections of the bulletin summarize background and trial-level evidence for numerous investigational therapies (for example, γ‑secretase inhibitors, monoclonal antibodies, intranasal insulin, IVIG, and neuromodulation), but these narrative segments do not themselves state discrete coverage determinations. They are presented as evidence summaries to inform clinical judgment and policy decisions rather than as standalone coverage rules.

Interpretation of the evidence is limited by heterogeneity across studies, including small numbers of trials for many interventions, variable subject characteristics (age, disease severity, biomarker selection), differing outcome measures and follow‑up durations, and varied intervention protocols. These methodological differences restrict the ability to draw broad conclusions about efficacy for several experimental therapies.

The bulletin’s additional information pages provide administrative material, external links, and a copyright/disclaimer statement. These sections do not add new coverage exclusions for clinical interventions; they include standard disclaimers that Clinical Policy Bulletins are informational and do not constitute an offer of coverage or medical advice.

The bulletin’s primary coverage stance is that the enumerated treatments (items 1–65) are considered experimental/investigational for Alzheimer’s disease because their effectiveness for this indication has not been established; as such, these interventions are treated as not medically necessary for routine clinical care outside approved research protocols.

Examples across multiple trial programs illustrate the policy rationale: semagacestat worsened functional outcomes and increased adverse events; large simvastatin and other statin trials showed no cognitive benefit; low‑flow CSF shunting was futile and associated with infections; and monoclonal antibody programs (for example, bapineuzumab, solanezumab, and verubecestat) failed to demonstrate consistent clinical efficacy in pivotal trials—findings that support the investigational and noncoverage posture for these therapies.

Bapineuzumab and solanezumab produced biomarker effects in some studies but did not translate into statistically significant improvements on primary clinical endpoints in phase III trials; safety considerations (for example, ARIA and vasogenic edema) further complicate their clinical use outside trials.

The policy urges avoidance of routine clinical use for agents lacking positive pivotal evidence—citing solanezumab, idalopirdine, H3 antagonists, and raloxifene among others—as these therapies have not shown reliable cognitive or functional benefit in randomized controlled studies.

Specific negative findings reported include no significant ADAS‑Cog differences for raloxifene at 12 months, no functional benefit for adding 2 years of home‑based occupational therapy to collaborative care, and no proof‑of‑concept for edonerpic maleate at tested doses—supporting their experimental classification.

Edonerpic maleate phase II results (safety population n=482) showed ADAS‑Cog mean changes at 52 weeks that were not significantly different from placebo and higher discontinuation for adverse events in active groups, leading to the conclusion that clinical proof‑of‑concept was not demonstrated.

The document does not convert each narrative evidence summary into a separate formal 'not medically necessary' statement within the cited chunks; instead, it consistently frames the interventions as investigational and highlights the need for further high‑quality randomized data to support routine coverage.

The CODING section aggregates the experimental/not‑covered codes into a single code group for administrative use. The listed codes include procedural, device, infusion, drug and ICD‑10 diagnosis codes that correspond to many of the interventions identified as experimental in this policy and are referenced for claims processing.

Coding — Not Covered / Experimental Codes and Key Score Ranges

Not covered / Experimental CPT codesCPTNot Covered

0780T	Instillation of fecal microbiota suspension via rectal enema into lower gastrointestinal tract.
36514	Therapeutic apheresis; for plasma pheresis.
36516	With extracorporeal selective adsorption or selective filtration and plasma reinfusion.
38240	Hematopoietic progenitor cell (HPC); allogeneic transplantation per donor.
38241	Autologous transplantation.
38242	Allogeneic lymphocyte infusions.
44705	Preparation of fecal microbiota for instillation, including assessment of donor specimen.
61863	Twist drill, burr hole, craniotomy, or craniectomy with stereotactic implantation of neurostimulator electrode array in subcortical site; first array.
61864	Each additional array (List separately in addition to primary procedure).
61867	With use of intraoperative microelectrode recording; first array.

1–10 of 30

1/3

Key score ranges

ADAS-Cog score range0 to 70 (higher scores indicate greater cognitive impairment)

Key score ranges

ADCS-ADL score range0 to 78 (higher scores indicate better functioning)

Provider Actions — Prior Authorization, Documentation, and Denial Risk

Prior Authorization

Prior Authorization Required for Listed Experimental Therapies

Prior authorization is expected for high-cost, procedural, or device-based experimental Alzheimer’s therapies listed as investigational. Providers should obtain approval before scheduling or administering these interventions to avoid claim denials.

Applies to listed procedures and devices (e.g., CPT/HCPCS codes in policy)
Includes implantable neurostimulator procedures and other billed services tied to investigational therapies

Denial Risk

CSF Shunt — Potential Noncoverage and Safety Risk

CSF shunting (continuous drainage of cerebrospinal fluid / ventriculo-peritoneal shunt) is considered experimental and was halted for futility in randomized trials; it is likely to be noncovered. Expect denials based on lack of clinical benefit and safety concerns (increased CNS infections).

Randomized trial stopped for futility (Silverberg et al., 2008)
Associated with higher-than-expected CNS infections — safety concern

Prior Authorization

Prior Authorization / Coverage Support Needed for Experimental BACE Inhibitors and Anti‑Amyloid Infusions

Experimental disease‑modifying interventions targeting amyloid (BACE inhibitors and similar agents) generally require prior approval/supporting coverage evidence. Multiple BACE inhibitors (e.g., lanabecestat, verubecestat) had trials discontinued for futility or showed no clinical benefit; coverage decisions should be supported by strong evidence and explicit authorization.

Lanabecestat: global phase‑III program discontinued (June 2018)
Verubecestat: large RCT terminated early for futility and increased adverse events
Bapineuzumab and other anti‑amyloid infusions failed to show clinical benefit and had ARIA safety signals

Denial Risk

Evidence‑Based Denial Triggers

Evidence-based denial triggers include: RCTs and meta-analyses showing no clinical benefit, early termination for futility, and trial safety signals. Providers should expect noncoverage or denials for interventions with this evidence profile.

Multiple phase III trials (e.g., solanezumab, bapineuzumab) failed to meet primary clinical endpoints
Trials halted early for futility (e.g., verubecestat, CSF shunt)
Safety signals such as amyloid‑related imaging abnormalities (ARIA), increased infections, or other AEs may trigger denials

Note

No Explicit Prior Authorization or Coverage Denial Rule Specified in Parts of the Policy

Some sections of the source material provide background or billing/code lists without specifying a formal prior authorization or coverage denial rule. In such cases, follow payer prior authorization procedures and check current benefit plan language.

CPT/HCPCS/ICD lists in policy serve as not‑covered examples but do not replace formal authorization rules
Supplemental/administrative sections do not include explicit authorization criteria

Step Therapy

Step‑Therapy — No Requirements Specified

No step‑therapy or step‑requirement rules are specified for the investigational agents in the provided content. Standard symptomatic therapies (cholinesterase inhibitors, memantine) are described as preferred, but the policy does not mandate stepwise trials before considering investigational treatments.

Preferred standard therapies: cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and memantine
No documented step‑therapy sequence or required prior trials for experimental agents in extracted content

Documentation Required

Documentation Required to Support Requests for Investigational Therapies

When pursuing coverage for investigational therapies (trials, off‑label use, high‑cost infusions/devices), providers should supply protocol or enrollment documentation, clinical outcome measures, and safety monitoring information to support medical necessity reviews.

Provide clinical assessments used in trials (e.g., ADAS‑Cog, MMSE, ADCS‑ADL, CDR‑SB)
Include imaging and biomarker data where available (PIB‑PET, CSF Aβ/tau)
Supply study protocol, informed consent, enrollment/eligibility documentation, and safety monitoring plans

Background — Disease, Trials, and Investigational Therapies

Investigational Treatments — evidence summary (background)

Background context and trial-level evidence summarizing multiple investigational interventions discussed across the policy

Heterogeneous investigational landscape: The document reviews a broad range of interventions (pharmacologic, biologic, device-based, behavioral and complementary) with variable evidence quality ranging from preclinical to phase III randomized trials; many agents showed biomarker effects or preclinical promise but lacked consistent clinical efficacy.

See multiple background chunks summarizing individual therapies and trials

Common themes in evidence: Across interventions, small sample sizes, methodological heterogeneity, inconsistent outcome measures, and mixed safety signals limit strong conclusions; therefore, routine coverage is not supported for most experimental therapies outside of research settings.

Supported by trial summaries in chunks 36–47, 54–57, 72–83

Coverage for investigational therapies (conditional) — background details and trial outcomes

Background details and trial outcomes relevant to conditional coverage and denial considerations

Trials halted or negative (denial-relevant): Several large trials were stopped for futility (e.g., verubecestat) or failed to meet primary endpoints (e.g., solanezumab, bapineuzumab, edonerpic maleate, crenezumab), reducing support for routine coverage of these agents.evidence of futility/negative RCTs

See chunks 56–57, 77, 83, 90

When coverage is considered (research context only): If provided within a recognized clinical trial or approved research protocol with IRB oversight, documented enrollment, and prespecified safety monitoring and outcome assessments, coverage may be considered contingent on submission of protocol and monitoring documentation.

Reflects conditional coverage requirements summarized in the policy

Safety and monitoring expectations: For therapies with known safety signals (e.g., ARIA with anti-amyloid antibodies, increased infections with CSF shunting), documentation of MRI/CSF monitoring and adverse event reporting per protocol is required.

See chunks 45–47, 37, 42

Definitions and Key Terms

inv-60: Definition — Alzheimer disease (AD)

DefinitionA neurologic condition marked by progressive loss of mental abilities severe enough to interfere with activities of daily living, typically occurring in adulthood with cognitive decline over at least six months.

inv-61: Definition — Semagacestat

Drug class and targetSemagacestat — a small-molecule γ-secretase (gamma-secretase) inhibitor investigated as a potential treatment for Alzheimer's disease.

Key trial outcomeIn a double-blind randomized trial (Doody et al 2013; n=1,537) semagacestat did not improve cognition and was associated with worsened functional ability and increased adverse events, including skin cancers and infections.

Safety signalsAssociated laboratory abnormalities (reduced lymphocytes, T cells, immunoglobulins, albumin, total protein; elevated eosinophils, monocytes, cholesterol) and increased rates of serious adverse events and treatment discontinuations.

inv-62: Definition — Vagus nerve stimulation (VNS)

DefinitionVagus nerve stimulation (VNS) — surgically implanted electrical stimulation of the vagus nerve intended to modulate brain activity.

Evidence summarySmall open-label pilot studies (e.g., Sjögren et al 2002, n=10) reported responder rates on ADAS-Cog and MMSE and generally favorable tolerability; longer-term follow-up showed some patients improved or did not decline at 1 year, but evidence is preliminary.

Clinical implicationFurther controlled studies are needed; current evidence insufficient to support routine coverage.

inv-63: Definition — Semagacestat (alternate chunk mapping)

Semagacestat safety detailSemagacestat was associated with worsened functional ability and more adverse events, including skin cancers and infections, and laboratory abnormalities; it did not improve cognitive status compared with placebo.

inv-64: Definition — VNS (pilot/open-label evidence notes)

Pilot/open-label evidence noteVNS pilot studies reported median improvements in ADAS-Cog and MMSE scores at 3–6 months and tolerability over 1 year, but sample sizes were small and further trials were recommended.

inv-65: Definition — Intravenous immunoglobulin (IVIG)

DefinitionIntravenous immunoglobulin (IVIG) — pooled human immunoglobulin preparations that contain anti–Aβ antibodies and have been evaluated as a potential passive immunotherapy for AD.

Pilot dataA pilot study (Dodel et al 2004, n=5) reported decreased CSF total Aβ and increased serum total Aβ after monthly IVIG over 6 months with a small ADAS-Cog improvement, but sample size was too small to draw conclusions.

inv-66: Definition — Low-flow ventriculo-peritoneal shunt

DefinitionLow-flow ventriculo-peritoneal shunt — a surgically implanted shunt intended to continuously drain cerebrospinal fluid to improve clearance of CNS macromolecules.

Trial outcomeA randomized, double-blind, sham-controlled trial (Silverberg et al 2008; n=215) was halted for futility; no between-group differences in primary outcomes and the procedure was associated with 12 CNS infections.

inv-67: Definition — Amyloid-related imaging abnormalities (ARIA)

DefinitionAmyloid-related imaging abnormalities (ARIA) — MRI-detected abnormalities (including vasogenic edema and microhemorrhages) observed with anti-amyloid monoclonal antibody therapy.

Clinical relevanceARIAs were a notable safety finding in bapineuzumab trials and increased with dose and APOE ε4 allele number, sometimes leading to dose discontinuation.

inv-68: Definition — ADAS-cog / ADAS-cog14

DefinitionADAS-cog / ADAS-cog14 — Alzheimer's Disease Assessment Scale–cognitive subscale; commonly used cognitive outcome with ADAS-Cog11 range 0–70 and ADAS-Cog14 range up to 90, where higher scores indicate greater impairment.

Use in trialsPrimary cognitive outcome in multiple phase II/III antibody and drug trials (e.g., solanezumab EXPEDITION trials and Honig et al phase III), with reported mean changes used to assess efficacy.

inv-69: Definition — MMSE

DefinitionMini-Mental State Examination (MMSE) — a cognitive screening test scored 0–30 with higher scores indicating better cognition; used to define mild dementia populations in trials (e.g., MMSE 20–26 in solanezumab trial).

inv-70: Definition — Gamma frequency band

DefinitionGamma frequency band — neuronal oscillations roughly between 30 Hz and 100 Hz (40 Hz often emphasized) targeted by external stimulation modalities.

Therapeutic contextModulation of gamma-band activity via external stimulation is a novel noninvasive approach under investigation with preliminary preclinical and limited clinical data.

inv-71: Definition — BACE1 inhibitor

DefinitionBACE1 inhibitor — oral agents that inhibit beta-site amyloid precursor protein cleaving enzyme 1 to reduce production of amyloid-β peptides (examples: lanabecestat, verubecestat).

Clinical noteLarge phase III trials of BACE inhibitors (e.g., verubecestat) were terminated for futility or failed to show clinical benefit despite lowering Aβ biomarkers and were associated with adverse events.

inv-72: Definition — ADAS-Cog

DefinitionADAS-Cog — Alzheimer's Disease Assessment Scale–Cognitive subscale, a commonly used cognitive outcome measure in AD trials.

Related measuresOften reported alongside ADCS-ADL and CDR-Sum of Boxes in trial outcome assessments.

inv-73: Definition — CDR-Sum of Boxes (CDR-SB)

DefinitionCDR-Sum of Boxes (CDR-SB) — Clinical Dementia Rating scale summed boxes, a functional/clinical severity measure used in AD and MCI trials.

inv-74: Definition — Medium-Chain Fatty Acids (MCFA)

DefinitionMedium-Chain Fatty Acids (MCFA) — dietary fatty acids hypothesized to increase brain energy metabolism; further research is needed to determine if this improves cognition in AD.

inv-75: Definition — Music therapy / Active Music Intervention (AMI)

DefinitionMusic therapy / Active Music Intervention (AMI) — non-pharmacological interventions involving music listening or participation; AMI (active music-making) showed greater cognitive effects in some randomized trials.

Evidence limitationsSystematic review identified 8 RCTs (689 participants) with heterogeneity in interventions, outcomes, and methods; further research needed to define optimal approach and long-term effects.

Revision History

2024-02-20Last reviewLatest

Policy was last reviewed on 02/20/2024.

2009-06-19Effective date

Policy became effective on 06/19/2009.

Supplementary administrative pages included with the bulletin provide policy history, links to the glossary and other resources, and a copyright/disclaimer statement; these pages do not introduce new clinical coverage exclusions and reiterate that the CPB is informational and subject to change.